>> GOOD MORNING, EVERYONE.
MY NAME IS ZHAOXIA REN, PROGRAM
OFFICER AT THE OBSTETRICS,
PEDIATRIC BRANCH IN THE EUNICE
KENNEDY SHRIVER CHILD HEALTH AND
HUMAN DEVELOP M THE.
I'M ONE OF THE COORGANIZERS AND
CO-CHAIRS FOR THIS WORKSHOP,
ALONG WITH THE OTHER TWO
CO-CHAIRS, DR. MELISSA
FOUNDATION FOR THE NIH AND
DR. HANI FAYSAL FROM INDIANA
UNIVERSITY.
IT IS OUR GREAT PLEASURE TO
WELCOME YOU TO JOIN US TODAY FOR
THIS EXCITING WORKSHOP THAT IS
AIMING FOR A FASTER DISCUSSION
AND SHARE THE KNOWLEDGE IN THE
MATERNAL HEALTH BY BRIDGING --
IN BRIDGING OF GAPS AND
LEVERAGING EXISTING RESOURCES IN
BIOREPOSITORIES AND LABORATORIES
AND ALSO USING CUTTING EDGE
TECHNOLOGIES.
SO IT IS -- WE ARE SO THRILLED
FOR ALL OF YOU TO COME HERE
TODAY TO LOOK FORWARD TO THE
EXCITING DISCUSSION AND
PRESENTATIONS.
SO BEFORE WE START, I'D LIKE TO
ANNOUNCE A FEW HOUSEKEEPING
ITEMS.
SO TODAY'S WORKSHOP IS RECORDED
SO PLEASE WHEN YOU HAVE A
QUESTION OR MAKE A COMMENT,
PLEASE TURN ON YOUR MICROPHONE,
DIRECTLY SPEAK TO THE
MICROPHONE, AND FOR FOLKS
JOINING ON ZOOM AND ALSO PLEASE
TURN ON YOUR CAMERA AND SO AFTER
YOU FINISH, TURN OFF THE
MICROPHONE, UNMUTE YOURS UR -- D
MUTE YOURSELF.
FOR SOME OF YOU I GUESS FIRST
TIME BEING ON THE CAMPUS AND FOR
THIS BUILDING, SO IT IS A LITTLE
BIT COMPLICATED.
SO THE BATHROOMS, YOU GO OUT AND
TO THE HALLWAY AT THE RIGHT AND
WHEN YOU GET OUT TO THE
ELEVATOR, YOU'LL SEE THE SIGN ON
YOUR RIGHT-HAND SIDE, THERE'S
BATHROOMS, AND FOR MOST
IMPORTANT, FOR THE LUNCH IS
UNFORTUNATELY WE COULDN'T GET
ENOUGH ORDERS FOR A BOX LUNCH TO
CATER TO US SO -- BUT THERE IS A
CAFETERIA, THE FIRST FLOOR, SO
YOU GET DOWN TO OLE VAI TORE TOG
HALLWAY TO THE END, TURN LEFT
THERE IS A CAFETERIA, AND ALSO
THERE'S A CONCESSION STAND FOR
SANDWICHES, CHIPS OR COOKIES,
WATERS OR OTHER DRINKS, AND SO
PLEASE FEEL FREE TO ASK
QUESTIONS IF YOU HAVE ANY
QUESTIONS, YOU GET LOST IN THE
BUILDING.
ANYWAY.
SO WITH THAT, WITHOUT FURTHER
ADO, I'D LIKE TO KICK IT OFF BY
INTRODUCING THE OPENING REMARKS
SPEAKERS.
FORTUNATELY WE HAVE THREE
DISTINGUISHED SPEAKERS FOR
OPENING REMARKS.
FIRST IS DR. ALISON CERNICH.
DR. CERNICH IS THE DEPUTY
DIRECTOR FOR NICHD AND WORKS TO
SUPPORT THE INSTITUTE'S MISSION
TO LEAD RESEARCH AND TRAINING TO
UNDERSTAND HUMAN DEVELOPMENT,
IMPROVE ROW PRODUCTIVE HEALTH
AND ENHANCE THE LIVES OF
CHILDREN AND ADOLESCENTS AND
OPTIMIZE ABILITIES FOR ALL.
PRIOR TO THIS POSITION,
DR. CERNICH WAS THE DIRECTOR OF
THE NATIONAL CENTER FOR MEDICAL
REHABILITATION RESEARCH, NCMRR
AT NICHD, DEPUTY DIRECTOR OF THE
CENTERS OF EXCELLENCE FOR
PSYCHOLOGICAL HEALTH AND
TRAUMATIC BRAIN INJURY IN THE
DEPARTMENT OF DEFENSE, AND SHE
ALSO HELD MULTIPLE ROLES IN THE
DEPARTMENT OF VETERANS AFFAIRS.
SHE IS A BOARD CERTIFIED
NEUROPSYCHOLOGIST.
THE SECOND SPEAKER FOR THE
OPENING REMARKS IS DR. STACEY
ADAM.
DR. ADAM IS VICE PRESIDENT AT
THE FOUNDATION FOR THE NIH.
SHE LEADS MANY PUBLIC PRIVATE
PARTNERSHIPS SUCH AS
ACCELERATING COVID-19
INTERVENTION AND VACCINES, THE
BIOMARKERS CONSORTIUM, CANCER,
STEERING COMMITTEE, ACCELERATING
MEDICINE PARTNERSHIP, METS BOLG
DISEASES, PARKINSON'S DISEASE,
PARTNERSHIP FOR ACCELERATING
CANCER THERAPY.
AND CLINICAL TRIALS.
PRIOR TO FOUNDATION -- DR. ADAM
WAS A MANAGER AT THE CONSULTING
IN FEDERAL LIFE SCIENCE AND
HEALTHCARE STRATEGY PRACTICE,
WHERE SHE SUPPORTED MANY FEDERAL
AND NON-PROFIT CLIENT PROJECTS.
OUR THIRD SPEAKER FOR THE
OPENING REMARKS IS DR. AARON
PAWLYK.
DR. PAWLYK IS CHIEF OF OBSTETRIC
BRANCH AT THE NICHD AND HE'S MY
BOSS.
AND DR. PAWLYK IS A
PHARMACOLOGIST WITH DECADES OF
LEADERSHIP EXPERIENCE IN DRUG
DISCOVERY AND PRE-CLINICAL
DEVELOPMENT PHARMACOGENOMICS AND
MATHEMATICAL MODELING ACROSS
MULTIPLE THERAPEUTIC AREAS.
UNDER HIS LEADERSHIP, THE OPPTB
AIMS TO ASSURE THAT THERE ARE
SAFE AND EFFECTIVE THERAPEUTICS
FOR CHILDREN AND PREGNANT
LACTATING WOMEN AND THAT THESE
MEDICATIONS ARE USED OPTIMALLY
ACCORDING TO INDIVIDUAL NEEDS.
BEFORE JOINING NIH, HE HELD
MULTIPLE POSITIONS IN THE
PHARMACEUTICAL SECTORS.
WITH THAT, I'D LIKE TO TURN IT
OVER TO DR. ALISON CERNICH.
>> I JUST WANT TO THANK ZHAOXIA
SO MUCH.
AM I OKAY TO STAY UP HERE?
I'M GOING UP FRONT?
OKAY.
HOLD, PLEASE.
OKAY, I'M GOOD HERE.
ALL RIGHT.
SO I'M THE DEPU DEPUTY DIRECTORF
NICHD, AND I REALLY JUST FIRST
OFF WANT TO THANK THOSE OF YOU
IN THE ROOM AND THOSE OF YOU
JOINING US VIRTUALLY.
I'M VERY EXCITED TO BE HERE TO
DISCUSS OUR WORK ON MATERNAL
HEALTH AND REALLY T DO APPRECIAE
EVERYONE'S TIME AND EFFORT.
I ALSO WANT TO THANK THE
ORGANIZERS.
THESE MEETINGS DO NOT COME OFF
WITHOUT A TON OF WORK, SO THANK
YOU FOR ALL YOU'VE DONE TO
COORDINATE THIS AND PUT THIS
TOGETHER.
DR. MELISSA REYES FROM THE
FOUNDATION, THANK YOU SO MUCH
FOR ALL THAT YOU'VE DONE, AND
ALSO DR. HANI FAYSAL FROM
INDIANA UNIVERSITY, ALSO THANK
YOU FOR YOUR EFFORTS.
I THINK THIS WAS SAID ALREADY,
IF YOU'RE NOT FAMILIAR WITH
NICHD, WE DO A LOT OF WORK ON
MATERNAL HEALTH.
60% OF WHAT IS DONE HERE AT NIH
ON MATERNAL HEALTH COMES FROM
OUR BUDGET.
AND SO WHILE IT'S NOT IN OUR
NAME, WHICH TENDS TO CONFUSE
PEOPLE, I THINK OUR MISSION AND
OUR VISION REALLY DO SET THIS UP
NICELY AND REALLY OUR RESEARCH
SPANS FROM VERY EARLY
DEVELOPMENT THROUGH ADULTHOOD SO
WE CAN ENSURE HEALTHY
PREGNANCIES, HEALTHY CHILDREN
AND HEALTHY OPTIMAL LIVES FOR
ALL.
AS PART OF OUR MISSION, WE FUND
RESEARCH TO ADVANCE MATERNAL
HEALTH AND HEALTHY PREGNANCIES
AND IMPROVE MATERNAL AND INFANT
OUTCOMES, AND THIS INCLUDES NOT
ONLY FUNDAMENTAL BIOLOGY BUT
ALSO CLINICAL INTERVENTIONS,
WORK IN THE SOCIAL AND
BEHAVIORAL SCIENCES, AS WELL AS
PHARMACOLOGIC RESEARCH AND
TECHNOLOGICAL INNOVATION.
WE ALSO LEAD A LOT OF
INITIATIVES ACROSS THE FEDERAL
GOVERNMENT, AND SO FOR EXAMPLE,
I SERVE ON THE HEALTH AND HUMAN
SERVICES TASK FORCE ON MATERNAL
MENTAL HEALTH.
I ALSO SERVE ON THE MATERNAL
HEALTH LEADERSHIP COORDINATING
COMMITTEE.
AND THESE REALLY SUPPORT MAJOR
EFFORTS, FOR EXAMPLE, AT THE
WHITE HOUSE, BLEUT PRINT FOR --E
BLUEPRINT FOR MATERNAL HEALTH
AND WE'LL TALK A LITTLE ABOUT
SPECIFIC INITIATIVES AT NICHD
MORE.
SO I JUST WANT TO TALK A LITTLE
BIT ABOUT OUR INVESTMENTS HERE.
SO THIS IS OUR OVERALL FUNDING
FOR MATERNAL HEALTH.
WE WERE AT ABOUT -- SORRY, TAKE
THAT BACK.
WE REPRESENT 35% OF THE OVERALL
NIH TOTAL.
FLIPPED THE NUMBERS.
SO THE ALIGNMENT WITH THE NICHD
MISSION, WE ARE REALLY ONE OF
THE MAJOR FUNDERS HERE, JOINED
OBVIOUSLY BY OTHERS, INCLUDING
THE OTHER LARGE FUNDERS,
NATIONAL HEART, BLOOD AND LUNG
INSTITUTE, NATIONAL INSTITUTE OF
MENTAL HEALTH ACTUALLY FUNDS
QUITE A BIT, AND REALLY DROVE
DISCOVERY OF A NEW DRUG FOR
POSTPARTUM DEPRESSION.
SO WE REALLY HAVE BEEN TRYING
ALSO TO ACCELERATE OUR
INVESTMENT.
AS YOU CAN SEE THIS HAS GROWN
OVER THE PAST COUPLE OF YEARS
AND THIS IS REALLY IN RESPONSE
TO THE RISING MATERNAL MORBIDITY
AND MORTALITY RATES IN THE
UNITED STATES.
WE ARE REALLY TRYING TO DRIVE
SOLUTIONS TO DRIVE DOWN THOSE
NUMBERS.
AND AGAIN, APOLOGIES FOR
FLIPPING OUR NUMBERS BEFORE, WE
ARE AT 35% OF OVERALL FUNDING,
AND AGAIN NHLBI, NIAID, NIDA,
NIMHD AND OTHERS REALLY LEADING
THE CHARGE HERE.
BUT MANY OTHER INSTITUTES
REPRESENTED, AND WE DO HAVE
QUITE A BIT OF COORDINATION AT
THE NIH WRIT LARGE, SO NICHD
WORKS WITH THE NATIONAL
INSTITUTE OF NURSING RESEARCH IN
THE OFFICE OF RESEARCH OND
WOMEN'S HEALTH TO REALLY
COORDINATE THE COORDINATING
COMMITTEE FOR MATERNAL MORBIDITY
AND MORTALITY, WHICH BRINGS
TOGETHER ALL OF THESE INSTITUTES
TO TALK ABOUT OUR EFFORTS IN
MATERNAL HEALTH.
SO WE'RE WORKING ON OUR
STRATEGIC PLAN, WE'RE CURRENTLY
OPERATING UNDER OUR 2020 NICHD
STRATEGIC PLAN, WHICH INCLUDED
FIVE OVERARCHING SCIENTIFIC
RESEARCH THEMES, TWO OF WHICH
PERTAIN SPECIFICALLY TO MATERNAL
HEALTH.
REALLY WHAT WE HAVE BEEN DOING
SINCE THIS PLAN'S LAUNCH IS
REALLY WORKING TOWARD
ESTABLISHING AND ACHIEVING THESE
GOALS, SO THIS INCLUDES
CONTINUED WORK WITH OUR TASK
FORCE ON RESEARCH SPECIFIC TO
PREGNANT AND LACTATING WOMEN OR
PRGLAC AND THAT FOCUSES ON GAPS
IN KNOWLEDGE AND RESEARCH
REGARDING SAFE AND EFFECTIVE
THERAPIES AND VACCINES FOR
PREGNANT AND LACTATING WOMEN.
WE ARE LOOKING AT THIS
SPECIFICALLY NOW AS A REFRESH,
AND SO I'M SURE AARON AND HIS
TEAM WILL BRING SOME OF WHAT WE
DO HERE BACK TO THE PLAN
DISCUSSIONS THAT WE'RE HAVING
FOR OUR 2025 STRATEGIC PLAN.
AND WE ARE ACTUALLY BASING A LOT
OF THIS NOW, WE HAVE BEEN
SIMULTANEOUSLY WORKING ON AN
IMPLEMENTATION FOR OUR STRATEGIC
PLAN AND TRACKING DATA ON HOW
WELL WE'RE DOING ADVANCING THESE
METRICS.
SO I THINK IF WE HAVE SOME
ACTIONABLE THINGS THAT WE CAN
DO, WE'D LOVE TO HEAR THAT FROM
YOU ALL.
SO WHAT HAVE WE BEEN DOING TO
INVEST IN MATERNAL HEALTH
INFRASTRUCTURE?
FIRST AND FOREMOST, WE HAVE BEEN
WORKING SINCE 2019 ON THE
IMPLEMENTING OF MATERNAL HEALTH
AND PREGNANCY OUTCOMES VISION
FOR EVERYONE PROGRAM OR
INITIATIVE OR WHAT WE CALL
IMPROVE.
THIS EFFORT IS CO-LED BY US, BY
NINR AND THE OFFICE OF RESEARCH
ON WOMEN'S HEALTH.
WE ARE REALLY ARE FOCUSED ON
REDUCING PREVENTABLE CAUSES IN
MATERNAL DEATHS AND IMPROVING
HEALTH OF WOMEN BEFORE AND AFTER
DELIVERY.
THIS HAS A SPECIFIC EMPHASIS ON
HEALTH DISPARITIES IN
POPULATIONS THAT ARE
DISPROPORTIONATELY AFFECT BID
MATERNAL MORBIDITY AND
MORTALITY.
THERE ARE REALLY A NUMBER OF
COMPONENTS TO THIS PROGRAM, AND
IT ACCELERATED PRETTY QUICKLY
WHEN WE RECEIVED AN
APPROPRIATION IN 2022 FOR THIS
PROGRAM FROM CONGRESS.
SO WHAT HAVE WE DONE HERE?
ESSENTIALLY, IN '23, WE AWARDED
A PROVIDE MAX ALL RIGHT
$24 MILLION TO FUND 10 RESEARCH
CENTERS OF EXCELLENCE WHICH
AIMED TO DEVELOP, IMPLEMENT AND
EVALUATE COMMUNITY TAILORED
INTERVENTIONS TO ADDRESS
MATERNAL HEALTH DISPARITIES.
WE ALSO INCLUDED IN THAT
TRAINING AND PROFESSIONAL
DEVELOPMENT SO THAT WE CAN
REALLY FOSTER THE NEXT
GENERATION OF RESEARCHERS IN
THIS AREA.
WE HAVE ALSO BEEN WORKING ON A
RADX TECH PROGRAM.
FOR THOSE FAMILIAR WITH OUR WORK
DURING COVID TO ADVANCE
DIAGNOSTICS THROUGH THE NATIONAL
INSTITUTE OF BIOMEDICAL IMAGING
AND BIOENGINEERING, THEY PUT
TOGETHER A COMMERCIALIZATION
PROGRAM TO GET THINGS
ESSENTIALLY FROM CONCEPT TO
COMMERCIAL APPLICATION, AND
THEY'VE NOW RETOOLED THAT
PROGRAM SO WE CAN USE IT FOR
OTHER DIAGNOSTICS AND POINT OF
CARE AND OTHER TECHNOLOGIES.
WE HAVE BEEN AS NIBIB SAID ONE
OF THEIR BEST CUSTOMERS BECAUSE
WE FIND IT'S THE BEST WAY FOR US
TO DRIVE SORT OF NOVEL
TECHNOLOGIES IN A SPACE THAT
PEOPLE DON'T GIVE A LOT OF
ATTENTION AND WE CAN BRING IN
NEW RESEARCHERS SO WE REALLY ARE
TRYING TO DEVELOP REMOTE
TECHNOLOGIES TO IMPROVE MATERNAL
HEALTH OUTCOMES FOR THOSE LIVING
IN AREAS THAT LACK ACCESS TO
MATERNITY CARE.
MANY OF YOU KNOW THERE ARE A
NUMBER OF MATERNITY CARE DESERTS
IN THIS COUNTRY AND REALLY WITHE
HAVE 10 TEAMS NOW MOVING TOWARDS
FINAL STAGES WITH TECHNOLOGIES
AND THE WINNERS WILL BE
ANNOUNCED THIS FALL.
AND LASTLY, THE CONNECTATHON IS
THE WORK WE'RE DOING WITH THE
OFFICE OF THE NATIONAL
COORDINATOR IN HEALTH AND HUMAN
SERVICES.
THIS IS ONE OF THE WAYS WE ARE
TRYING TO GET STANDARDS TO BE
USED FOR REAL WORLD DATA IN THE
ELECTRONIC HEALTH RECORD.
SO THROUGH THIS GROUP, WE'VE
PILOTED HL7 FIRE STANDARDS,
DEVELOPED IMPLEMENTATION GUIDE
AND ACTUALLY PILOTED THIS IN
HEALTH INFORMATION EXCHANGES IN
THIS COUNTRY TO SEE ITS
FEASIBILITY.
WE'VE BEEN WORKING WITH
STAKEHOLDER GROUPS ON THIS FOR
QUITE SOME TIME, AND NOW ONC IS
PUTTING THIS INTO THEIR UNITED
STATES CORE DATA FOR
INTEROPERABILITY AND THEY'RE
PUTTING TOGETHER A SPECIFIC SET
FOR MATERNAL HEALTH.
THIS ALLOWS US TO REQUIRE THINGS
IN ELECTRONIC HEALTH RECORD THAT
ALLOW STANDARDIZATION.
SO FOR THOSE OF YOU WHO WORK IN
REAL WORLD DATA, I THINK THIS IS
A GREAT ADVANCE THAT WE'RE DOING
WITH THE GROUP THAT CAN ACTUALLY
MANDATE TA FOR THE HEALTH
RECORD.
WE ACTUALLY, IN A VERY HARD
BUDGET YEAR, WERE RECOGNIZED I
THINK BY CONGRESS AS HAVING DONE
A LOT SO WE GOT AN ADDITIONAL
$10 MILLION THIS YEAR SO WE ARE
REALLY WORKING TO PUT THAT MONEY
TO GOOD USE AND EXPANDING A
LITTLE BIT IN MATERNAL HEALTH
TOWARDS INTERPERSONAL INTIMATE
PARTNER VIOLENCE, AS WELL AS
SOME OF THE SYSTEM FACTORS THAT
DRIVE MATERNAL HEALTH
DISPARITIES.
JUST TO HIGHLIGHT TWO OTHER
THINGS WE REALLY TRY TO LEVERAGE
HERE, WE HAVE SOME FAIRLY ROBUST
AND LONGSTANDING NETWORKS THAT
REALLY HAVE LAID THE FOUNDATION
FOR MUCH OF OUR WORK, INCLUDING
THE MATERNAL-FETAL MEDICINE
UNITS AND THE NEONATAL RESEARCH
NETWORK, SO THE MFM U-CONN DUCTS
MULTISITE CLINICAL TRIALS ON
PREGNANCY COMPLICATIONS,
PHARMACOLOGY AND EMERGING ISSUES
TO IMPROVE CARE AND THIS HAS
BEEN A VERY SUCCESSFUL NETWORK.
WE ALSO WERE ABLE TO LEVERAGE IT
DURING COVID-19 TO LOOK AT REAL
WORLD TREATMENTS USING THEIR
DATA.
SIMILARLY, THE NEONATAL RESEARCH
NETWORK OR NRN, WE'VE REALLY
BEEN ABLE TO WORK WITH THEM TO
ADVANCE NEWBORN HEALTH TO LOOK
AT TREATMENT AND MANAGEMENT
STRATEGIES FOR NEWBORN INFANTS
AND WE HAVE MADE SOME
SIGNIFICANT CHANGES TO CLINICAL
PRACTICE BECAUSE OF THEIR WORK.
WE'VE RECENTLY RESTRUCTURED THE
NETWORKS TO ALLOW FOR GREATER
ACCESS FOR THE INVESTIGATOR
COMMUNITY, SO IT USED TO BE THAT
YOU HAD TO BE PART OF THE
NETWORK TO HAVE TRIALS IN THIS
NETWORK.
NOW AT THIS POINT, WHAT YOU CAN
DO IS ANY QUALIFIED INVESTIGATOR
CAN SUBMIT AN APPLICATION FOR
MULTISITE STUDIES THROUGH A
SPECIFIC PAR, WHICH WE CAN GET
TO YOU, AND THAT WAY WE'VE
OPENED THIS NETWORK TO THE
LARGER COMMUNITY FOR CLINICAL
TRIAL INFRASTRUCTURE.
I KNOW AARON IS EXCITED ABOUT
THIS ONE BECAUSE THIS IS HIS
FAVORITE PROGRAM.
THIS IS THE MPRINT HUB, THE
MATERNAL AND PEDIATRIC PRECISION
IN THERAPEUTICS HUB, AND THIS IS
FROM HIS BRANCH, THE OPPTB.
THEY'VE REALLY DONE THIS TO JUST
QUEUE UP A NATIONAL RESOURCE FOR
EXPERTISE IN MATERNAL AND PETE
TRPEDIATRIC THERAPEUTICS, TO
EXPAND THE AVAILABLE KNOWLEDGE
TO THE BROADER RESEARCH,
REGULATORY SCIENCE AND DRUG
DEVELOPMENT COMMUNITIES.
IT ALSO CONDUCTS
THERAPEUTICS-FOCUSED RESEARCH IN
OBSTETRICS, LACTATION AND
PEDIATRICS, AND REALLY DOES MAKE
AN EFFORT TO INCLUDE PEOPLE WITH
DISABILITIES.
WHICH IS ALSO A MAJOR PART OF
OUR MISSION.
THERE ARE THREE ENTITIES WITHIN
THIS.
THERE IS THE TWO CENTERS OF
EXCELLENCE IN THERAPEUTICS AT
THE UNIVERSITY OF CALIFORNIA
SAN DIEGO IN VANDERBILT AND A
PARTNERSHIP BETWEEN INDIANA AND
OHIO STATE UNIVERSITY THAT SERVE
AS THE CENTRAL COORDINATING
CENTER FOR THE HUB.
SO AGAIN, I THINK WE HAVE A LOT
OF INFRASTRUCTURE FOR THOSE OF
YOU WHO ARE REALLY TRYING TO
DRIVE KNOWLEDGE IN THIS AREA
THAT I THINK CAN BE LEVERAGED.
SO I ALSO JUST WANT TO HIGHLIGHT
THAT WE HAVE BUILT OVER TIME THE
NICHD DATA AND SPECIMEN HUB.
THIS IS A REALLY KEY RESOURCE,
ESPECIALLY AS WE'VE MOVED INTO
THIS DATA SHARING AND MANAGEMENT
POLICY WHICH SOME OF YOU I AM
SURE HAVE EMBRACED
WHOLEHEARTEDLY WITH LOVE AND
GREAT CARE.
I THINK THAT THIS IS A
CENTRALIZED RESOURCE THAT YOU
CAN USE TO SHARE DE-IDENTIFIED
DATA FROM STUDIES RELEVANT TO
OUR POPULATIONS.
THIS IS A CONTROLLED ACCESS
REPOSITORY.
SO PEOPLE DO HAVE TO DO A DATA
USE AGREEMENT AND GO THROUGH A
PROCESS IN ORDER TO OBTAIN THESE
DATA, AND WE CAN ALSO PROVIDE
BIOSPECIMENS FROM SELECTED
STUDIES IN DASH.
THOUGH WE HAVE ABOUT -- I GUESS
AT THIS POINT, OVER 220 STUDIES
OR -- WELL, IT'S 227 STUDIES,
AND THIS REALLY COVERS
EVERYTHING FROM BREAST MILK TO
INFANT CARE TO PHARMACOLOGY,
BLOOD AND BREAST MILK ARE
AVAILABLE IN THE BIOSPECIMENS.
AND THERE'S -- THE WEBSITE IS
BELOW.
WE'RE ALSO TRYING TO GET NEW
STUDIES IN THERE THAT ARE LARGE
STUDIES THAT ARE CHALLENGING THE
TECHNOLOGY A LITTLE BIT THAT WE
HAVE.
BUT WE'RE HOPING TO GET THE NEW
MOM TO BE STUDY AVAILABLE
THROUGH DASH, WHICH ENROLLED
MORE THAN 10,000 PREGNANT PEOPLE
TO UNDERSTAND POTENTIAL
PREDICTORS OF ADVERSE PREGNANCY
OUTCOMES AND INCLUDES A NUMBER
OF MATERNAL CHARACTERISTICS AS
WELL AS PLACENTAL DEVELOPMENT,
AND THEN OTHER CHARACTERISTICS
OF THE FETUS.
WE ALSO HAVE DATA ON GESTATIONAL
WEIGHT GAIN AND ACCULTURATION.
NHLBI HAS THE FOLLOW-ON STUDY TO
THIS IN THE NEW MOM TO BE HEART
HEALTH STUDY, WHERE THEY'RE
LOOKING AT FOLLOW-ON FOR RISK
FOR CARDIOVASCULAR DISEASE AND
THEY'RE ALSO LOOKING AT SLEEP
WITHIN THAT STUDY NOW.
AND THEN AGAIN, THIS IS -- I
HIGHLIGHTED THIS EARLIER, BUT
THIS IS THE MATERNAL AND INFANT
HEALTH INFORMATION FOR RESEARCH
IMPLEMENTATION.
THIS IS AN HL7 FIRE STANDARD
THAT IS AVAILABLE THROUGH THEIR
WEBSITE AND YOU CAN GET TO THAT
IMPLEMENTATION GUIDE.
THIS WAS A TWO-YEAR-LONG EFFORT
REALLY TO TRY TO GET US TO SOME
STANDARDS AROUND PREGNANCY SO WE
CAN USE REAL WORLD DATA.
WE ALSO DURING COVID HAVE WORKED
TIRELESSLY TO THINK ABOUT COMMON
DATA ELEMENTS FOR MATERNAL
HEALTH RESEARCH AND REALLY
THINKING ABOUT THIS AS ANOTHER
WAY TO STANDARDIZE AND GET
COMPARABLE DATA.
WE WERE TASKED WITH DEVELOPING A
LIST OF CDs FOR USE IN
PREGNANCY STUDIES AND WE ARE
DOING THAT THROUGH THE MATERNAL
HEALTH RESEARCH CENTERS OF
EXCELLENCE.
THEY ARE NOW VALIDATING SOME OF
THE CDEs THAT WE DEVELOPED.
THEY'RE IN THE FIRST ROUND OF
DELPHI VOTING TO PRIORITIZE
CONSTRUCTS AND THEY'RE GOING TO
PROVIDE FINAL RECOMMENDATIONS BY
FALL OF THIS YEAR SO PLEASE FEEL
FREE TO CHECK OUT THE MATERNAL
HEALTH RESEARCH CENTERS OF
EXCELLENTS, THEY'LL HAVE MORE
INFORMATION THERE.
SO I THINK HONESTLY AT THIS
POINT, I REALLY THANK YOU FOR
WHAT YOU'RE DOING.
I WANT YOU TO KNOW THAT WE'RE
TRYING TO HAVE AS MUCH
INFRASTRUCTURE AND DATA AND
OTHER THINGS AVAILABLE FOR YOU
ALL TO FURTHER YOUR WORK.
AND I'M REALLY M HONORED THAT YU
ALL ARE HERE BRINGING YOUR IDEAS
AND THOUGHTS AND JUST SOME KEY
QUESTIONS, YOU KNOW, WHAT
RESOURCES AND INFRASTRUCTURE DO
WE NEED?
WE'VE DONE A LOT.
IS THERE SOMETHING MISSING?
ARE AARE THERE GAPS AND OPPORTUS
IN SHARED COLLABORATION THAT WE
CAN TACKLE?
I JUST WENT THROUGH A WHOLE
BUNCH OF STUFF.
IF YOU DON'T KNOW ABOUT IT AND
YOU'RE REALLY KNOWLEDGEABLE IN
THIS AREA THAT TELLS ME A LOT OF
PEOPLE DON'T KNOW ABOUT IT AND
WE NEED TO GET RESOURCES MORE
WIDELY AVAILABLE, CAN YOU GIVE
US SUGGESTIONS ON HOW DO THAT?
AND THEN HOW CAN WE BETTER
PARTNER WITH INTERESTED
STAKEHOLDERS TO ACHIEVE COMMON
GOALS?
I WILL SAY THAT OUR PARTNERSHIP
WITH THE FOUNDATION IS ONE OF
THE WAYS THAT WE DO THAT.
I'M REALLY, REALLY GRATEFUL TO
HAVE THEIR PARTNERSHIP AND FOR
THEM TO BE HERE TODAY.
SO WITH THAT, I WILL END AND
TURN IT OVER, I BELIEVE TO
STACEY, CORRECT?
AWESOME.
THAT'S IT.
THANK YOU.
>> ARE YOU DRIVING OR ARE WE
DRIVING?
YOU CAN DRIVE?
GOOD.
ALL RIGHT.
SO WHILE ALISON WAS VERY GOOD IN
KIND OF SHOWING YOU EVERYTHING
THAT NICHD HAS DONE, I WILL SAY
THE FOUNDATION HAS BEEN IN THE
MATERNAL SPACE FOR LESS TIME,
BUT MOST OF THE WORK THAT WE DO
DO IN THE MATERNAL HEALTH SPACE
IS WORKING WITH NICHD AS ALISON
SAID, SO WE HOPE TO HAVE BEEN A
GOOD PARTNER IN THE PAST AND
HOPE TO CONTINUE TO BE A REALLY
GOOD PARTNER IN THE FUTURE.
WHAT I'M GOING TO TALK ABOUT IS
LESS KIND OF ON ALL THE
RESOURCES OUT THERE THAT WE HAVE
THEN BUT MORE ON THE IDEA OF
THINKING THE ART OF THE POSSIBLE
BECAUSE AS ALISON SAID, WE CAN
BE A MAJOR FACILITATION ABOUT
HOW WE BRING IN PRIVATE SECTOR
RESOURCES TO WORK WITH THE NICHD
RESOURCES AND TO JUST FACILITATE
GENERAL PARTNERSHIP.
SO VIEW THAT, THAT IS HOW MY
PRESENTATION IS GOING TO COME
DOWN.
SO FOR THOSE WHO DON'T KNOW WHAT
THE FOUNDATION IS, WE ARE A
501(C)3 FORMED BY CONGRESS WITH
THE ONLY MISSION TO HELP THE
NICHD PUBLIC PRIVATE
PARTNERSHIPS.
WHAT WE FIGURE IS SCIENCE HAS
THE POWER TO CURE A LOT OF
THINGS, BUT THERE ISN'T A SINGLE
ORGANIZATION THAT'S EVER GOING
TO DO THIS ALONE, AND THAT
INCLUDES THE NIH.
AS BIG AS IT IS, AS POWERFUL AS
IT IS, EVERYBODY IS STILL GOING
TO NEED HELP IN THIS SPACE.
SO HOW DO WE DO THIS?
WE HELP THE NIH PARTNER WITH
WORLD CLASS ORGANIZATIONS TO
TAKE ON THE BIGGEST CHALLENGES.
AS YOU HEARD FROM ALISON,
OBVIOUSLY MATERNAL HEALTH HAS
BECOME A FOCUS IN THE LAST FEW
YEARS, ESPECIALLY COMING OUT OF
THE WHITE HOUSE, SO WE WORK WITH
NIH, OTHER GOVERNMENT AGENCIES,
SO WHILE WE ARE THE FOUNDATION
FOR THE NIH, WE ARE ABLE TO
REACH ACROSS OTHER AGENCIES AND
ASSIST WHEN NECESSARY.
WE ALSO WORK WITH LIFE SCIENCES
AND ACADEMIA, AND OTHER
FOUNDATIONS AND PATIENT
ORGANIZATIONS.
SO ALL THREE OF THESE KIND OF
ECOSPHERES KIND OF COME TOGETHER
AND WE HOPE TO LEVERAGE WHO HAVE
NWHOEVERNEEDS TO BE AT THE TABLR
EACH PARTNERSHIP.
NOW AS I SAID, WE CAN WORK WITH
ANY OF THE 27 INSTITUTES AT THE
NIH, SO WHILE WE'RE HERE TALKING
ABOUT MATERNAL HEALTH, JUST KEEP
IN MIND WE DO HAVE KIND OF -- WE
RUN THE GAMUT AND I WOULD ARGUE
THAT WOMEN'S AND MATERNAL HEALTH
SWORD OF RUNS THE GAMUT AS WELL,
RIGHT, BECAUSE WE DO KNOW THAT
OFTENTIMES WOMEN ARE UNDERSERVED
IN MANY OF THESE SECTORS, EERCH
THOUGH WE'RE HEVENTHOUGH WE'RE T
KIND OF SPECIFIC THINGS.
SO WE'VE DONE THIS FOR ABOUT 25
YEARS NOW.
WE DO THIS QUITE WELL, WE'VE
RAISED OVER $1.5 BILLION TO
PARTNER ALONGSIDE A LOT OF THE
NIH INFRASTRUCTURE AND WORK.
WE HAVE 122 ACTIVE PARTNERSHIPS
ONGOING RIGHT NOW, AND WE DO
THESE IN THREE MAJOR BUCKETS.
WE HOPE TO ACCELERATE PREVENTION
OF NEW THERAPIES, DIAGNOSTICS
AND POTENTIAL CURES, SO THIS IS
WHERE A LOT OF MY TEAM IN
TRANSLATIONAL SCIENCE, WHERE A
LOT OF OUR WORK GOES.
THIS INCLUDES THE
ACCELERATING -- PARTNERSHIPS,
THE BIOMARKER CONSORTIUM,
ACCELERATING CANCER THERAPIES AS
WELL AS OUR WORK FOR COVID.
WE ALSO SEEK TO ADVANCE GLOBAL
HEALTH AND EQUITY IN CARE.
THIS IS WHERE SOME OF OUR WORK
WITH NICHD HAS BEEN DONE.
I WON'T TALK A LOT ABOUT IT NOW,
BUT ESPECIALLY THE A-PLUS TRIAL,
WHICH JUST WRAPPED UP ITS FIRST
PHASE IN AFRICA AND AGAIN, TALK
ABOUT GOOD RESULTS, A SINGLE
DOSE OF AZITHROMYCIN DURING
LABOR, WHAT WAS IT, 30, 40%
REDUCTION, 40% REDUCTION IN
MATERNAL MORTALITY.
JUST BASED ON THAT.
SO THINK ABOUT THAT.
A GENERIC DRUG THAT CAN BE GIVEN
ONCE, HOW POWERFUL THAT IS, WHAT
ELSE CAN WE FIND, AND THERE ARE
FOLLOW-ON STUDIES GETTING
PREPPED UP THAT WE'RE GOING TO
BE WORKING ON WITH NICHD IN THIS
AREA.
WE ALSO LIKE TO SUPPORT THE NEXT
GENERATION OF SCIENTISTS, SO WE
HAVE A NUMBER OF TRAINING AND
PRIZE AWARDS THAT WE DO THAT WE
GIVE OUT EACH YEAR AND SO IF YOU
AREN'T AWARE OF THESE, PLEASE DO
TAKE A LOOK AT THE WEBSITE.
I WON'T TALK MUCH ABOUT THEM
TODAY BUT THEY ARE OPEN ACROSS
VARIOUS BACKGROUNDS AND FIELDS.
SO WHAT DO WE DO, THE FNIH
SPECIFICALLY?
WE KIND OF DO WHATEVER NEEDED TO
DO.
SO WHEN WE BRING EVERYONE
TOGETHER UNDER THE BANNER, WE
PLAY THE NEUTRAL THIRD PARTY
BROKER.
WE OFTEN SAY THAT WE DON'T HAVE
A STAKE IN THE GAME.
OUR ONLY STAKE IN THE GAME IS TO
PROMOTE THE MOVEMENT FORWARD FOR
HUMAN HEALTH.
SO IF WE NEED DO GOVERNANCE AND
WE NEED TO HELP MANAGE AND WE
NEED TO BRING PEOPLE TOGETHER
FOR CONSENSUS AND DISCUSSION, WE
CAN DO THAT.
WE CAN HELP POLICY MANAGEMENT,
WE CAN HELP WRITE SPECIFIC
POLICIES FOR EACH PARTNERSHIP
THAT NEED TO BE THERE.
PROGRAM MANAGEMENT.
WE DO THIS QUITE WELL, WE DRIVE
THINGS FORWARD.
I OFTEN JOKE THAT WE PROBABLY
COULD BE HARASSERS IN CHIEF JUST
TO KEEP THINGS MOVING FORWARD.
FUNDRAISING, RELATIONSHIP
MANAGEMENT, WE DO A LOT OF THIS.
I KNOW MANY PEOPLE ESPECIALLY
THE PRIVATE SECTOR IN THIS ROOM
HAVE WORKED WITH US BEFORE AND
KNOW THAT WE WORK TO CULTIVATE
THOSE RELATIONSHIPS.
INTELLECTUAL PROPERTY
MANAGEMENT.
WE CAN ALSO DO THIS.
WE TRY TO KEEP OURSELVES IN THE
PRECOMPETITIVE SPACE BUT IT
DOESN'T MEAN WE CAN'T ASSIST IF
IP HAS TO BE DEALT WITH.
SO I'M GOING TO TALK A LITTLE
ABOUT THE BIOMARKERS CONSORTIUM
AND ONE OTHER PROJECT JUST
BECAUSE I THINK FOR SOME OF THE
EFFORTS THAT ARE GOING TO COME
FORWARD IN MATERNAL HEALTH THAT
WE'RE GOING TO BE WORKING WITH
THIS GROUP ON, IT'S PROBABLY
GOING TO FALL INTO ONE OF THE
TWO BUCKETS THAT I'M GOING TO
TALK ABOUT.
SO WHAT IS THE BIOMARKERS
CONSORTIUM?
AGAIN, HUGE VISION, IMPROVING
HEALTH THROUGH MEANINGFUL
MEASUREMENTS, WHAT DOES THAT
REALLY MEAN?
WE'RE BASICALLY JUST LEADING
CROSS SECTOR EFFORTS TO QUALIFY
BIOMARKERS AND TOOLS FOR DRUG
DEVELOPMENT, AND TO ACCELERATE
THINGS DOWN THE REGULATORY
SPACE.
WE'VE BEEN AT THIS AGAIN FOR A
NUMBER OF YEARS.
WE'RE COMING UP NEXT YEAR ON OUR
20TH ANNIVERSARY OF THE
BIOMARKERS CONSORTIUM.
WE'VE HAD NINE CLINICAL TOOLS,
FIVE FDA GUIDANCES, ONE
QUALIFIED BIOMARKER OF THE NINE
THAT THE FDA HAS QUALIFIED, WE
ACTUALLY HAVE ONE THAT CAME OUT
OF ONE OF OUR PROJECTS, AND AS
YOU CAN SEE, A NUMBER OF
PUBLICATIONS, CITATIONS, THAT
SORT OF THING, AND THIS IS JUST
FOR PERSPECTIVE, THIS IS OUR
CURRENT MEMBERSHIP FOR THE
BIOMARKERS CONSORTIUM.
THIS IS WHO COMES TO OUR TABLE,
TALKS TO US ABOUT THIS, AND IT
GOES ACROSS MULTIPLE DIFFERENT
AREAS, BUT DEFINITELY WE'RE ABLE
TO LEVERAGE ALL OF THOSE PEOPLE.
ONE OF THE THINGS AND I WON'T
TALK A LOT ABOUT THIS PROJECT
BUT DEFINITELY YOU CAN TALK TO
KARINA OR MELISSA IN THE ROOM IF
YOU WANT TO KNOW MORE IN
PARTICULAR BUT WE JUST LAUNCHED
EARLIER THIS YEAR BIOMARKER FOR
RISK AND STRATIFICATION OF EARLY
ONSET PRE-ECLAMPSIA THIS IS ONE
OF OUR FIRST KIND OF BIOMARKER
CONSORTIUM FORAYS INTO THE
MATERNAL HEALTH SPACE.
WE'RE VERY EXCITED AND VERY
HAPPY TO HAVE THIS LAUNCHED AND
WE HOPE THAT IT WILL BE ONE OF
MANY PROJECTS THAT WE GET TO
WORK WITH NICHD ON IN THIS
SPACE.
THE OTHER PARTNERSHIP FORMAT
THAT I'M GOING TO TALK ABOUT IS
THE ACCELERATING MEDICINES
PARTNERSHIP.
WHEREAS THE BIOMARKERS IS
FOCUSED A LOT ON BIOMARKER AND
TOOL DEVELOPMENT AND REGULATORY
SPACE.
THINK ABOUT THIS AS TARGET
IDENTIFICATION AND VALIDATION,
SO THESE ARE OUR BIG DATA
PROJECTS THAT WE PUT TOGETHER.
SO ALL OF THAT LOVELY DATA
INTEROPERABILITY AND PIECES THAT
ALISON WAS TALKING ABOUT, WE'RE
PUSHING FORWARD IN THIS SPACE.
WE HAVE 10 ACCELERATING
MEDICINES PARTNERSHIPS.
34 INDUSTRY PARTNERS, TOTAL
INVESTMENT OF 134 --
$834 MILLION.
WE'VE BEEN AT THIS ONE FOR 10
YEARS.
WE JUST CELEBRATED OUR 10-YEAR
ANNIVERSARY AT THE START OF THE
YEAR.
WE HAVE CERTAIN OF THE
INSTITUTES AND 37 NON-PROFITS
THAT PARTICIPATE IN THESE.
AS YOU CAN SEE THEY GO ACROSS A
NUMBER OF DIFFERENT DISEASE
AREAS, ALZHEIMER'S, COMMON
METABOLIC DISEASE, AUTOIMMUNE
AND IMMUNE MEDIATED DISEASES,
PARKINSON'S, HEART FAILURE, A
LOT OF THINGS THAT ACTUALLY PLAY
IN WOMEN'S AND MATERNAL HEALTH
EVEN THOUGH THEY'RE NOT
SPECIFICALLY NAMED THERE.
WE'RE GETTING READY TO LAUNCH
NEW EFFORTS IN ALS AS WELL AS
CELL THERAPY, AND THE ONE DOWN
THERE SBI, THE SYSTEMS BIOLOGY
OF INFLAMMATION, THIS IS GOING
TO BE OUR FIRST FORAY INTO DATA
INTEROPERABILITY.
WE'RE TRYING TO TAKE THE DATA
FROM MANY OF THESE OTHER AMPS,
UNIFY THEM TOGETHER TO STUDY
CROSS PLATFORMS.
IN PARTICULAR THIS IS FOR
INFLAMMATION, BUT WHAT I WOULD
LIKE TO HIGHLIGHT THERE IS THAT
ONCE WE HAVE ALL THOSE DATA
TOGETHER, AND WE CAN START
PULLING IN OTHER DATA MAYBE FROM
NICHD RESOURCES, IMAGINE WHAT WE
COULD FIND ACROSS ALL OF THAT
DATA, INFLAMMATION AND OTHERW
OTHERWISE.
SO THIS IS JUST A PITCH, WHY
WOULD YOU WANT TO COME WORK WITH
US?
WE START WITH THE GOAL IN MIND,
SO UNLIKE NIH, WE DON'T GET A
CONGRESSIONAL APPROPRIATION.
PEOPLE COME TO US WITH AN IDEA,
WHETHER THAT BE NIH OR ONE OF
THE PRIVATE SECTORS, WE LISTEN,
WE CONVENE THE STAKEHOLDERS, WE
TRY AND FIGURE OUT WHAT THE
SPECIFIC NEED FOR A PARTNERSHIP
IS IN THAT AREA.
WE THEN DESIGN AND SCOPE THE
PARTNERSHIP TO WHAT WE THINK
WOULD BE SUCCESSFUL, ACTIVATE BY
ENGAGING AND BRINGING IN ALL THE
PARTNERS AND THEN WE MANAGE IT
FROM LAUNCH TO IMPACT.
THAT IS WHERE WE ARE GOING TO
BE, AND WE INTENTIONALLY ARE
DOING MUCH MORE FOLLOW-UP TO SEE
WHAT OUR IMPACT HAS BEEN FOR ALL
THE PROJECTS THAT WE'VE MANAGED
OVER THE LAST 25 YEARS AND WE'RE
GOING TO BE DOING A LOT MORE OF
THAT MOVING FORWARD.
SO WITH ALL THAT SAID, THANK YOU
VERY MUCH FOR LISTENING AND I
HOPE YOU'LL KEEP THE FNIH IN
MIND ESPECIALLY FOR THE PRIVATE
SECTORS IN THE ROOM WHEN YOU
WANT TO COME WORK WITH US IN
NICHD AND I'LL TURN IT OVER TO
AARON PAWLYK.
>> FIRST THING I WANT TO DO, A
LITTLE BIT OF HISTORY OF WHERE
THIS WORKSHOP CAME FROM AND A
DEFINITELY SOME THANKS.
SO IT'S ACTUALLY THE KICK YOFER
OF THAT PREECLAMPSIA BIOMARKER
PROJECT THAT STACEY MENTIONED,
WE WERE SITTING AROUND AND I
MENTIONED, HEY, MELISSA, HANI,
SASHA, MAYBE YOU COULD GET
TOGETHER AND WE COULD HAVE CALL
OR HALF DAY OR SOMETHING TALKING
ABOUT BIOSAMPLE STANDARDS.
SO THE WORKSHOP TODAY IS A VAST
IMPROVEMENT ON THAT INITIAL IDEA
I PUT OUT THERE, SO A LOT OF
THANKS TO THEM FOR REALLY
DEVELOPING THIS INTO SOMETHING
FAR MORE SUBSTANTIAL THAN WAS
THE INITIAL SEED THAT WAS
PLANTED.
SO THEY'RE VERY GOOD GARDENERS.
WHAT I WANT TO DO TODAY IS SORT
OF FRAME THIS IN TERMS OF WHERES
TO THIS FIT IN SORT OF THE
BROADER ECOSYSTEM, WHAT ARE WE
TRYING TO DO BIG PICTURE AND
SPECIFICALLY TODAY, WHAT WE'RE
GOING TO TALK ABOUT AND THEN
SOME SPECIFIC OUTCOMES.
WE'RE NOT GOING TO SOLVE
EVERYTHING TODAY, WE'RE NOT
GOING TO FIGURE OUT EVERYTHING
WE NEED TO DO TODAY SO KEEP THAT
IN MIND IF WE CAN FIGURE SOME
THINGS OUT, GREAT.
WE'RE GOING TO HAVE FOLLOW-ON
CONVERSATIONS AND FOLLOW-ON
ACTIVITIES.
WHAT I WANT TO TALK ABOUT NOW IS
HOW WE GET TO NOVEL THERAPEUTICS
FOR ADVERSE PREGNANCY OUTCOMES
AND THE ROLE OF WHAT WE'D LIKE
TO CREATE AND WHAT WE'RE GOING
TO TALK ABOUT TODAY.
ALL RIGHT.
SO WHEN I THINK ABOUT NOVEL
DRUGS FOR ADVERSE PREGNANCY
OUTCOMES I THINK ABOUT IT AS A
FOUR-LEGGED STOOL -- OR
THREE-LEGGED STOOL.
THERE'S THREE THINGS WE REALLY
NEED TO BE SUCCESSFUL HERE.
FIRST IS IMPROVE NON-CLINICAL
SAFETY MODELS AND ASSESSMENT.
THE OTHER IS QUALIFIED
BIOMARKERS.
AND THE OTHER IS DRUG TARGET
VALIDATION.
SO VERY BRIEFLY ON THE
NON-CLINICAL MODELS BECAUSE
THAT'S NOT OUR FOCUS TODAY BUT I
DO WANT TO HIGHLIGHT HERE THE
FACT THAT THE NICHD DOES SUPPORT
A VARIETY OF RESEARCH
INITIATIVES IN THIS AREA.
OFTEN IN PARTNERSHIP WITH OTHER
INSTITUTES SUCH AS NCATS, THAT'S
THE FIRST GRANT, AND WE HAVE ONE
OF THE INVESTIGATORS HERE TODAY
THAT WILL BE SPEAKING AND
LEADING SOME SESSIONS LATER.
JUST ON THE LEFT HERE IS
ACTUALLY A PHOTO FR FROM THE
PROJECT.
THAT'S A MICROPHYSIOLOGICAL
SYSTEM LOOKING AT TRANSPORT
ACROSS THE PLACENTAL BARRIER.
THERE'S ALSO AN NIH COMMON FUND
PROGRAM CALLED COMPLEMENTARIE TO
DEVELOP NOVEL APPROACH
METHODOLOGIES OR NEW APPROACH
METHODOLOGIES TO SERVE IN THIS
NON-CLINICAL SPACE.
SO THE NICHD IS VERY ACTIVE IN
THIS PROGRAM.
IT'S CURRENTLY BEING SCOPED OUT
BY THE COMMON FUND SO WE'LL KEEP
EVERYBODY IN THE LOOP BECAUSE
THIS MAY BE ANOTHER WAY TO GET
TO SOME OF THOSE NEW MODELS.
BRIEFLY, I WANT TO INTRODUCE A
YOU?
NETWORK THAT THE NICHD IS
KICKING OFF.
THIS IS THE NIH TRANSPORTER
ELUCIDATION NETWORK, WHICH WE'RE
FUNDING IN CONJUNCTION WITH THE
NATIONAL INSTITUTE OF DRUG ABUSE
AS WELL AS THE OFFICE OF DIETARY
SUPPLEMENTS.
THIS IS FOCUSED ON SPECIFICALLY
SLC AND ABC TRANSPORTERS, AND
HOW THEY FUNCTION ESSENTIALLY TO
GET NUTRIENTS, DRUGS,
ENVIRONMENTAL COMPOUNDS, FROM
MOM TO BABY OR MOM TO FETUS.
THIS IS CURRENTLY COMPOSED OF
FOUR CENTERS.
I'M NOT GOING TO GO THROUGH
THESE IN DETAIL.
IF ANYBODY IS GOING TO ASPT IN A
COUPLE WEEKS, WE ACTUALLY HAVE A
SESSION ON SUNDAY ABOUT THAT,
BUT THIS REALLY STARTS TO FILL
IN SOME OF THE BASIC SCIENCE
AROUND TRANSPORT THAT WE'RE
GOING TO NEED TO UNDERSTAND FOR
THOSE NON-CLINICAL MODELS.
THE SECOND STOOL QUALIFIED
BIOMARKERS.
THIS IS THE PROJECT THAT STACEY
MENTIONED THAT A LOT OF WORK
WENT INTO IN GETTING THIS KICKED
OFF.
WHAT I WANT TO EMPHASIZE HERE IN
THE BOTTOM HERE IS THE FACT THAT
THIS IS FOCUSING ON TWO
ANGIOGENIC BIOMARKERS, PLGF AND
PAPP-A.
THIS IS A REALLY IMPORTANT
PROJECT THAT G GOING TO LOOK ATA
VERY ETHNICALLY DIVERSE NORTH
MEARN COHORT TO TRY TO QUALIFY
THESE BIOMARKERS IN THE U.S. VIA
THE FDA, WHICH ARE AVAILABLE IN
OTHER COUNTRIES.
THESE ARE USED IN A LOT OF OTHER
COUNTRIES BUT WE DON'T HAVE
REGULATORY APPROVAL AND THE DATA
TO SUPPORT THAT IN AMERICA.
SO THAT'S WHAT THIS PROJECT
FOCUSES ON.
SPECIFICALLY THESE ARE THE
PARTNERS OF THIS PROGRAM, JUST
SO YOU CAN SEE.
I BELIEVE SOME OF THEM MAY BE
HOPEFULLY WATCHING OR IN
ATTENDANCE TODAY.
SO THAT'S REALLY SORT OF
BRINGING AMERICA AND THE U.S.
AND OUR PATIENTS TO CURRENT
EXISTING LEVELS OF PREDICTION
FOR PRE-ECLAMPSIA I DON'T WANT
TO TALK TOO MUCH ABOUT THE
MPRINT HUB PER SE.
WE'LL HEAR TALKS FROM MEMBERS OF
THAT GROUP AND ALISON PRESENTED
A LITTLE BIT ON THAT.
WHAT I DO WANT TO HIGHLIGHT AND
YOU'LL HEAR MORE ABOUT THIS WHEN
HANI TALKS IS THROUGH THAT, WE
WERE ABLE TO CREATE A REPOSITORY
CALLED THE COLLABORATIVE ONLINE
PERINATAL AND PEDIATRIC
REPOSITORY.
WHICH HAS REALLY BEEN FOCUSING
ON FINDING AND IDENTIFYING WHAT
ARE EXISTING BIOBANKS THAT WE
CAN LEVERAGE, WHAT HAVE WE
ALREADY COLLECTED, WHAT DO
PEOPLE HAVE IN THEIR FREEZERS.
THE IT'S CURRENTLY FOCUSED ON
RETROSPECTIVE SAMPLE ANALYSIS.
SO THAT'S ONE THING THAT WE'RE
FOCUSING ON.
WE ALSO WANT TO BE A LITTLE BIT
MORE FORWARD-THINKING AND REALLY
THINK ABOUT WHAT ARE THE NEW
TECHNOLOGIES, WHAT ARE THE NEW
FUTURE BIOMARKERS, ESPECIALLY
ONES THAT CAN GET TO DISEASE
HETEROGENEITY.
I THINK MOST PEOPLE WOULD AGREE,
PREECLAMPSIA IS PROBABLY NOT ONE
MONOLITHIC DISORDER, IT PROBABLY
HAS MULTIPLE SUBTYPES AND THERE
IS SOME EVIDENCE THAT SUPPORTS
THAT AND A THAT'S LIKELY TRUE
FOR ALL IF NOT MOST OTHER
ADVERSE OUTCOMES.
WE'LL TALK MORE ABOUT THIS
LATER, I DON'T WANT TO TALK
ABOUT IT NOW, BUT IT WAS ANOTHER
PROJECT THAT THROUGH THE M PRINT
HUB AND ITS TRANSLATIONAL
RESOURCE RESEARCH PLATFORM,
WE'RE STARTING TO MOVE IN THAT
DIRECTION.
THAT'S DEFINITELY SOMETHING I
WANT US TO THINK ABOUT MORE
TODAY, WHAT ARE THE
TECHNOLOGIES, AND THAT'S WHY WE
HAVE A LOT OF TALKS ON THESE NEW
INNOVATIVE TECHNOLOGIES AND
APPROACHES.
SO REALLY THINKING ABOUT WHAT
ARE THE NEXT GENERATIONS OF
BIOMARKERS, ESPECIALLY IF THEY
CAN BE LINKED TO DISEASE
SUBTYPES WITH SPECIFIC DRUG
PATHWAYS THAT COULD BE TARGETED.
SO NEXT UP I WANT TO TALK A
LITTLE BIT ABOUT DRUG TARGET
VALIDATION.
BEFORE I DIVE INTO THAT OR HOW
WE DO THAT ON A LARGER SCALE,
THE NICHD THROUGH THE SBIR AND
STTR PROGRAMS, WHICH WE VIEW AS
AMERICA'S SEED FUND FOR
COMPANIES AND PROJECTS, WE DO
SUPPORT A FAIR NUMBER OF NOVEL
THERAPEUTICS FOR OBSTETRICS
CONDITIONS AND SEVERAL ARE
LISTED HERE.
THESE ARE ALL COMPANIES.
THIS IS NOT ALL INCLUSIVE AND
YOU CAN DO A SEARCH FOR THIS
THROUGH THE NIH REPORTER TOOL IF
YOU WANT TO SEE MORE
COMPREHENSIVE ANALYSIS OF THAT,
SO THERE'S A LOT OF REALLY COOL
SCIENCE GOING ON HERE.
BUT WHAT I WANT TO FOCUS ON IN
THE CONTEXT OF THIS WORKSHOP AND
WHAT I WANT EVERYBODY TO THINK
ABOUT HOW WE DO THAT ON A LARGER
SCALE AND HOW DO WE GET TO
LARGER SCALE VALIDATION THAT
WOULD MAKE THE LARGE
PHARMACEUTICAL COMPANIES IN THE
WORLD INTERESTED IN THESE
TARGETS AND THESE BIOMARKERS.
SO AS ALISON MENTIONED, DASH IS
A RESOURCE WHICH THE NICHD HAS
WHICH HOSTS A HUGE AMOUNT OF
DATA, A LARGE AMOUNT OF BIOSES
BIOSPECIMENS AS WELL AND WE CAN
BE THINKING ABOUT THAT SOME
THROUGHOUT THE DAY.
I ALSO WANT TO -- AS WELL AS THE
BIOMARKER CONSORTIUM, CITY SEE
DID INTRODUCE THE ACCELERATING
MEDICINES PARTNERSHIP PROGRAMS.
THESE VERY OFTEN HAVE KNOWLEDGE
BASES AND ANALYSIS PLATFORMS
WHICH ARE COUPLED TO
IDENTIFYING, USING THOSE LARGE
SCALE DATASETS, ANALYTICAL
TOOLS, BIOSAMPLES, NEW COLLECTED
SAMPLES, T TO DO COMPLEX ANALYSS
TO GET TO THESE PATHWAYS, AND
THESE PATHWAYS, PROBABLY SAY
NETWORKS, THEY'RE VERY
COMPLICATED, THAT WILL YIELD
BIOMARKERS AND DRUG TARGETS, AND
DRUG TARGETS BROADLY.
SO WHEN I THINK ABOUT THIS ALL,
WHAT CAN WE USE THIS KNOWLEDGE
RESOURCE FOR AMONG OTHER THINGS,
IS REALLY LEVERAGING DATA
SCIENCE, ALL THESE PARTNERSHIPS,
TO GET TO DISEASE INSIGHTS
BECAUSE WE NEED TO CONTINUE TO
UNDERSTAND THE DISEASE,
BIOMARKERS, AS WELL AS
ADDITIONAL DRUG TARGETS.
SO CERTAINLY WE HAVE
REPOSITORIES, REGISTRIES AND
DATA WAREHOUSES, RIGHT, THE DATA
AND THE SAMPLES.
WE HAVE TOOLS, BE THEY
BIOCHEMICAL, ANALYTICAL OR
COMPUTATIONAL AND ALGORITHMS.
WE THEN GO FROM DATA TO
KNOWLEDGE.
AND FROM THAT KNOWLEDGE, WE THEN
WANT TO GET TO THESE DRUG
TARGETS AND BIOMARKERS OR
POTENTIAL DRUG TARGETS AND
BIOMARKERS THAT, YOU KNOW, WE
ALL WANT SO THAT WE CAN IMPROVE
HEALTH FOR PREGNANT INDIVIDUALS
AND THEIR CHILDREN.
I WANT TO HIGHLIGHT ONE APPROACH
THAT I THINK HAS BEEN PRETTY
SUCCESSFUL AND THAT'S THE HUMAN
GENETICS AMPLIFIER AND NOEL AND
JASON WILL BE TALKING ABOUT THIS
LATER TODAY.
THEY WERE ACTUALLY VERY KIND TO
GO AHEAD AND PUT TOGETHER A
LITTLE BIT OF A PILOT BETA
PORTAL ON THE REPRODUCTIVE
SYSTEM.
A LOT OF FOCUS ON COMMON
METABOLIC DISORDERS IN THIS
PORTAL, SO WORKING IN
GESTATIONAL DIABETES WAS A
PRETTY STRAIGHTFORWARD MOVE INTO
THAT.
SO THIS IS OUT THERE, IT'S SMALL
SCALE AND WAS DOB OUT O DONE OUF
KINDNESS MORE THAN FUNDING SO
THAT IS CERTAINLY SOME OF THE
THINGS WE THINK ABOUT.
SO THE GOALS FOR TODAY.
I DO WANT TO THINK SOME CONCRETE
GOALS AND I WAS LOOKING AT
ALISON'S QUESTIONS SLIDE WHEN I
PUT THIS TOGETHER TO DRILL DOWN
A LITTLE BIT MORE ON GOALS FOR
TODAY.
SO HOW DO WE LEVERAGE EXISTING
BIOREPOSITORIES, DATA KNOWLEDGE
PORTALS, AND WHAT DO WE NEED TO
BUILD?
WHAT KNOWLEDGE CAN WE OBTAIN
FROM EXISTING BIOSAMPLES, LET'S
LEVERAGE WHAT WE HAVE, ALL THESE
THINGS WE PUT IN FREEZERS FOR
YEARS, LINING YOUR GRANT, WE'RE
GOING TO COLLECT THIS AND THEN
WE'LL DO SOMETHING WITH THEM.
LET'S ALSO THINK ABOUT THE
FUTURE.
WHAT ARE THE BEST PRACTICES FOR
FUTURE BIOSAMPLE COLLECTION THAT
WE CAN TO TO MAXIMIZE KNOWLEDGE.
I'M SURE THERE ARE EMERGING
TECHNOLOGIES THAT THE SAMPLES WE
COLLECTED MAYBE EVEN LAST WEEK
ARE NOT -- WERE NOT COLLECTED OR
STORED IN A WAY THAT WE CAN USE
TO ANALYZE THEM.
SO I REALLY WANT TO THINK ABOUT
THAT AS STUDIES TO THE
MATERNAL-FETAL MEDICINE UNIT
NETWORK, THE NRN, OTHER
ENDEAVORS GO FORWARD, WE CAN
START COLLECTING SAMPLES AND
ANALYZING THEM IN MORE
INNOVATIVE WAYS.
AND THAT REALLY GETS TO
PREPARING FOR THOSE EMERGING
TECHNOLOGIES.
ALSO THINKING ABOUT THE DATA
SIDE OF THAT.
I'M NOT GOING TO USE THE
ABBREVIATION A.I. BECAUSE IT'S
TALKED ABOUT A LOT THESE DAYS
BUT A VARIETY OF DIFFERENT
APPROACHES.
AND WHAT CAN WE AGREE ON TODAY,
AND WHAT NEEDS CONTINUED
DISCUSSION, SO I FEEL LIKE WE'RE
DEFINITELY GOING TO HAVE
CONTINUED DISCUSSIONS IN A
VARIETY OF VENUES AROUND THIS AS
WE CONTINUE TO WORK THROUGH THIS
AND DEVELOP THINGS.
SO WE'LL COME BACK TO THIS A
LITTLE BIT IN THE DAY.
AS WE HAVE THE BREAKOUTS LATER
ORANGES I REALLY HOPE EVERYBODY
WILL KEEP THIS IN MIND.
AND THAT IS MY LAST SLIDE, SO I
KNOW WE'RE A LITTLE BIT OVER
TIME, SO I WANT TO TURN TO
HARINA TO RUN THE NEXT SESSION.
>> GOOD MORNING, EVERYONE.
MY NAME IS HARINA RAJA.
I'M A PROJECT MANAGER AT THE
FNIH AND I'M LEADING THE
BIOMARKERS CONSORTIUM PUBLIC
PROJECT IN PRE-ECLAMPSIA IT'S
TRULY A PLEASURE TO BE WITH YOU
TODAY AND THANK YOU TO THE
ORGANIZERS FOR GIVING ME THE
OPPORTUNITY TO MODERATE THE
FIRST SESSION ON EXISTING
BIOREPOSITORIES AND KNOWLEDGE
MORTALS.
SO WE HAVE ABOUT AN HOUR AND A
HALF FOR THE FIRST SESSION, 15
MINUTES PER SPEAKER.
WE HAVE A KE DEDICATED TIME FOR&
A OR PANEL DISCUSSION AT THE END
OF THE FIRST SESSION AND THEN
WE'LL GO FOR A 10-MINUTE MORNING
BREAK.
SO WE'LL KICK START OUR FIRST
SESSION WITH A TALK FROM
DR. HANI FAYSAL FROM INDIANA
UNIVERSITY, COLLABORATIVE ONLINE
PERINATAL AND PEDIATRIC
REPOSITORY, ALSO KNOWN AS
COPPER.
>> GOOD MORNING.
OKAY.
SO TODAY I'M HERE TO TALK ABOUT
COPPER, THE COLLABORATIVE ONLINE
PERINATAL AND PEDIATRIC
REPOSITORY.
OKAY.
SO A LITTLE BACKGROUND ON THE
PROJECT.
RARE DISEASES LIKE EARLY ONSET
PREECLAMPSIA, THEY ONLY OCCUR IN
ABOUT .5% OF PREGNANCIES, SO
EVENTUALLY RECRUITING PATIENTS
AND OBTAINING BIOSAMPLES TO
MORE -- TO STUDY THESE DISEASES
IN DEPTH BECOMES A PROBLEM WITH
THE LIMITED AVAILABILITY OF
THESE PATIENTS.
SO THERE IS A GAP THAT WAS
IDENTIFIED, AND THAT IS THERE IS
A LACK OF CENTRALIZED PUBLICLY
AVAILABLE RESOURCES TO
FACILITATE CONNECTION BETWEEN
RESEARCHERS SEEKING THESE
BIOSPECIMENS AND THE DATA THAT
IS ASSOCIATED WITH THESE
BIOSPECIMENS THAT IS AVAILABLE
TO USE.
SO IN AN ATTEMPT TO ADDRESS THAT
GAP, BY UNDERSTANDING THE AREA
OF SPECIMENS CURRENTLY BEING
STORED IN REPOSITORIES.
THIS WORK IS COMPLEMENTARY TO
EXISTING RESOURCES THAT WAS
PREVIOUSLY MENTIONED JUST LIKE
DASH, AND COPPER WILL HELPFUL
FILL THE MPRINT HUB'S GOAL, IN
ADDITION TO CATALYZING
INNOVATIVE MULTIDISCIPLINARY
RESEARCH TO FACILITATE MATERNAL
AND PEDIATRIC THERAPEUTICS.
AIMS.
WE HAVE THREE MAIN YOU AIMS, OUR
FIRST ONE BEING TO SCOUT.
WHEN I SAY SCOUT, I MEAN JUST
SEEING WHAT BIOPREPOS TRIES ARE
CURRENTLY AVAILABLE, WHAT KIND
OF SAMPLES ARE THEY CURRENTLY
HOLDING, AND WHAT KIND OF DATA
THAT IS ASSOCIATED WITH THESE
SAMPLES CURRENTLY AVAILABLE.
OUR SECOND AIM AFTER SCOUTING,
WE ANALYZE THE DATA.
WE HAVE TO DETERMINE THE
AVAILABILITY OF THE BIOSPECIMENS
AND TO ENABLE FUTURE STUDIES
THAT WILL EVALUATE EARLY
PREGNANCY BIOMARKERS FOR
DISEASES SUCH AS EARLY ONSET
PREECLAMPSIA AND OTHER LONG-TERM
MATERNAL AND PEDIATRIC OUTCOMES.
AFTER SCOUTING, ANALYZING.
WE WILL FINALLY INTEGRATE.
BY EXPLORING MECHANISMS FOR
MATERNAL, NEONATAL AND PEDIATRIC
DATA AND BIOSPECIMEN INTEGRA
INTEGRATION.
OUR PILOT PHASE STARTED A LITTLE
WHILE AGO.
WE STARTED WITH THE MFMU
STUDIES, THE BUILDING BLOCKS OF
PREGNANCY AND THE OHIO PERINATAL
REPOSITORY.
IT STARTED OUT BY SENDING THE
INITIAL SURVEYS TO THESE THREE
BIG BIOBANKS AND SOME OF THE
SUGGESTED CHANGES THAT WE GOT
THROUGH FEEDBACK WERE THE
WORDING OF QUESTIONS, THE
ABILITY TO PAUSE AND RESUME
SURVEYS LATER ON, AS TO AVOID
HAVING UNFILLED SURVEYS THAT
WOULD BE REDUNDANT.
EVENTUALLY.
AND THE ABILITY TO DOWNLOAD A
RECORD OF ALL THE SUBMITTED
ANSWERS.
THE CURRENT STATUS OF THE
PROJECT.
THIS IS CURRENTLY THE STATE OF
THE COPPER WEBSITE.
IT IS CURRENTLY ACTIVE ONLINE.
WE HAVE ABOUT 20 BIOBANK RECORDS
WITH TWO FUNCTIONS, CLASSICAL
AND A.I.
CLASSICAL BEING DIVIDED INTO A
FILTERING OPTION PRESENT ON THE
LEFT, IN ADDITION TO A REGULAR
SEARCH OPTION THAT IS PRESENT AT
THE TOP, AND THE A.I. FUNCTION
THAT IS POWERED BY AZURE API.
ON A GOOD NOTE, THE WEBSITE HAS
BEEN QUITE POPULAR.
WE'VE BEEN RECEIVING A TOTAL
NUMBER OF 500 PAGE VIEWS WHEN
I -- AT THE TIME OF THIS SCREEN
CAPTURE WITH SOME VISITS IN
EUROPE, SOME VISITS IN ASIA BUT
MOST OF THE VISITS ON THE WEST
AND EAST COAST OF THE U.S.
SO OUR FIRST FUNCTION WOULD BE
FILTERING.
HERE I CHOSE TO GIVE AN EXAMPLE
OF FILTERING BY CONDITIONS OF
FOCUS.
WE CHOSE THE HYPERTENSIVE AND
ENDOCRINE, AND IT WOULD SHOW UP
THE BIOBANKS THAT WOULD HAVE
SAID THAT THEY HAD SAMPLES
RELATED TO HYPERTENSIVE AND
ENDOCRINE DISEASES.
HERE THERE'S THE SECOND
DEMONSTRATION OF THE CLASSICAL
SEARCH FUNCTION, HERE I WAS
LOOKING AT PLACENTAL SAMPLES,
AND IT WOULD GIVE ME THE
PROJECTS THAT HAVE THE PLACENTAL
SAMPLES BY ALSO SUMMARIZING THEM
ON THE RIGHT.
AND FINALLY, A.I.
LIKE YOU WOULD DO WITH ANY
CHATGPT OR ANY/ALL TERNTIVE A.I.
SEARCH ENGINE, I WOULD JUST SAY
HELLO, I NEED HELP LOOKING AT
THIRD TRIMESTER CORD BLOOD
SAMPLES AND THE A.I. TOOL WOULD
SUMMARIZE THE RESULTS.
HERE WE HAVE ONE EXAMPLE.
ON THE SECOND SLIDE, I WAS
LOOKING AT BIOBANKS THAT HELD
MORE THAN 10,000 SAMPLES WITH
OVER 50% OF THEM AVAILABLE, AND
THE A.I. ASSISTANT BASICALLY
SUMMARIZED THE AVAILABLE DATA WE
HAVE ON HAND AND PRESENTED ME
WITH SEVERAL OPTIONS.
AND THIS IS AN EXAMPLE OF WHEN
YOU CLICK ON ONE OF THE
BIOREPOSITORIES THAT IS
PRESENTED ON THE RIGHT OF THE
SCREEN.
IT GIVES YOU MORE DETAILS OF THE
NAME, THE CONTACT EMAIL, WHAT
KIND OF SPECIMENS, NUMBER OF
PARTICIPANTS AND NUMBER OF
SPECIMENS, THE AGE AND SEVERAL
DETAILS, IN ADDITION TO THE
ABILITY TO COPY PASTE THE
CONTACT EMAIL AND TO ENABLE
COLLABORATIONS.
AND I JUST WANT TO GIVE A
SPECIAL THANKS TO DR. DAVID
HAAS, DR. QUINNEY AND DR. LANGE
LANG LI AND TO THOSE WORKING
WITH ME TO HELP DEVELOP THE
WEBSITE.
IF YOU WANT TO CONTRIBUTE TO THE
COPPER PROJECT, YOU COULD SCAN
THE QR CODE OR PICK UP SOME OF
THE SMALL CARDS THAT ARE PRESENT
ON THE TABLE OVER THERE AND TO
CLOSE OUT, THIS IS A PICTURE OF
A SMALL VILLAGE IN MY HOME
COUNTRY OF LEBANON.
THANK YOU.
>> OUR NEXT SPEAKER IS
DR. REBECCA CLIFTON FROM THE
GEORGE WASHINGTON UNIVERSITY,
AND HER TALK IS GOING TO BE ON
MATERNAL FETAL MEDICINE UNITS
NETWORK, PAST, CURRENT AND
FUTURE.
>> AND I MIGHT HAVE SCREWED YOU
UP BY SENDING YOU THE PDF.
I THINK IT JUST NEEDS TO BE
BIGGER.
BECAUSE IT'S SHOWING TWO SLIDES.
THERE YOU GO.
I SHOULD HAVE BEEN UP HERE WHEN
PEOPLE WERE -- OKAY.
SO WE'VE HEARD A LITTLE BIT
ABOUT THE MFMU NETWORK FROM A
COUPLE DIFFERENT GROUPS THUS FAR
BUT I JUST WANT TO GIVE KIND OF
JUST A VERY BRIEF OVERVIEW.
SO IT WAS INITIATED IN 1986 BY
NICHD.
IT IS A COLLABORATIVE GROUP OF
CLINICAL CENTERS, A DATA
COORDINATING CENTER AND NICHD,
AND IN OUR CURRENT GRANT CYCLE,
IT'S SEVEN YEARS FROM 2023, SO
WE WERE JUST FUNDED ABOUT A YEAR
AGO FOR SEVEN YEARS GOING
THROUGH 2030.
WE HAVE 14 CLINICAL CENTERS IN
THIS FUNDING CYCLE AND AN
ADDITIONAL 24 SUBSITES.
SO JUST TO TALK A LITTLE BIT
ABOUT NETWORK STUDIES, SO I KIND
OF BROKE IT OUT INTO PAST,
PRESENT AND FUTURE.
SO PAST, I'M CALLING STUDIES
THAT WERE COMPLETED, SO WE'VE
HAD 31 RANDOMIZED TRIALS AND 26
OBSERVATIONAL STUDIES.
STUDIES THAT ARE ONGOING SO WE
HAVE TWO RANDOMIZED TRIALS AND
TWO OBSERVATIONAL STUDIES.
AND IN FUTURE, SO THESE ARE
FUNDED AND IN IMPLEMENTATION BUT
NOT YET STARTED, WE HAVE ONE
RANDOMIZED TRIAL.
SO TALK A LITTLE BIT ABOUT THE
BIOREPOSITORY.
SO THE PAST, SO FOR DATA
STORAGE, ALL THE DATASETS ARE
KEPT AT THE MFMU DATA
COORDINATING CENTER, WHICH IS
GW.
SOME OF THE DATASETS ARE
AVAILABLE IN DASH, AND WE ARE
WORKING VERY HARD TO GET THROUGH
THE BACKLOG OF OLDER DATASETS TO
GET THOSE SUBMITTED TO DASH.
WHEN IT COMES TO THE BIOSPECIMEN
STORAGE, FOR ALMOST ALL OF THE
STUDIES, THEY ARE HOUSED AT THE
NICHD BIOREPOSITORY, WHICH IS
FISHER BIOINVEST BIOSERVICES, IE
THAT IS STILL THE CORRECT NAME.
SO FOR ALL OF THESE PAST
SAMPLES, ACCESS HAS ALWAYS BEEN
THROUGH THE MFMU NETWORK.
HOWEVER, JUST TO NOTE THAT NICHD
RETAINS ONLIER SHIP OF THE OWNES
AND THERE IS INTENT TO LINK THE
BIOSPECIMENS WITH DE-IDENTIFIED
DATA IN DASH.
SO I KNOW NICHD IS WORKING ON
THAT, SO I THINK MORE TO COME ON
THAT.
SO I THINK ONE OF THE THINGS WE
WERE ASKED TO TALK ABOUT IN THE
MORNING SESSION WAS CHALLENGES,
SO I INCLUDED SOME CHALLENGES.
SO ONE OF THE THINGS WITH OLDER
STUDIES, ESPECIALLY THOSE
COMPLETED BEFORE INFORMATION WAS
DETAILED AND CONSENT ABOUT DATA
SHARING IS THOSE OLDER CONSENTS
DO NOT MENTION DATA AND
BIOSPECIMEN SHARING, SO THAT'S
ONE CHALLENGE.
THE OTHER CHALLENGE IS FOR
STUDIES, THEY WERE ALL UNDER
LOCAL IRB REVIEW, SO INDIVIDUAL
SITES MIGHT HAVE CHANGED THEIR
CONSENT LANGUAGE AS IT RELATES
TO DATA AND BIOSPECIMEN SHARING
LANGUAGE.
SO EVEN WHEN LANGUAGE WAS PUT IN
FOR NEWER STUDIES, A SITE MIGHT
HAVE TWEAKED IT IN JUST A WAY
THAT MAKES IT UNAVAILABLE TO BE
PROVIDED TO EXTERNAL
INVESTIGATORS.
ANOTHER CHALLENGE IS FUNDING TO
CONDUCT BIOSPECIMEN ASSAYS,
INCLUDING BIOREPOSITORY FEES TO
PULL THE SAMPLES, AND THEN
DE-IDENTIFYING BIOSPECIMEN
LABELS WHEN SHARED WITH EXTERNAL
INVESTIGATORS.
THIS JUST HIGHLIGHTS SOME PAST
STUDIES WITH BIOSPES MESPECIMEN.
SO WE SAW A COUPLE OF THESE
NAMES WHEN WE SAW THE LIST FOR
COPPER.
I DON'T WANT TO GO THROUGH THE
DETAILS FOR THESE BUT JUST KIND
OF SHOW A GENERAL IDEA OF WHAT
KIND OF BIOSPECIMENS HAVE BEEN
COLLECTED.
I HAD TO USE LETTER
ABBREVIATIONS WHICH I'VE SPELLED
DOWN BEFORE BUT YOU CAN SEE FOR
A LOT OF OUR TRIALS, WE DO TRY
TO COLLECT SERUM AND PLASMA.
FOR SOME OF THEM WE DO COLLECT
URINE, SALIVA, DEPENDING ON WHAT
THE GOAL WAS OF THAT STUDY, WE
WOULD COLLECT WHOLE BLOOD FOR
DNA EXTRACTION.
AND WE ALSO TRY, BECAUSE WE'RE
DEALING WITH STUDIES IN
PREGNANCY AND THE OFFSPRING, WE
DO TRY TO COLLECT SAMPLES ON
BOTH THE MOMS AND THE INFANTS.
THIS IS JUST TWO MORE OF OUR
RECENTLY COMPLETED STUDIES.
YOU CAN SEE FOR THIS STUDY AND
ONE OF OUR ONGOING STUDY, WE DID
COLLECT VAGINAL SAMPLES.
VAGINAL SWABS, I SHOULD SAY, NOT
SAMPLES OF THAT.
SO JUST TO TALK A LITTLE BIT
ABOUT THE BIOREPOSITORY, SO
BIOSPECIMENS RIGHT NOW FOR OUR
ONGOING STUDIES ARE BEING STORED
AT THE INDIVIDUAL CLINICAL
CENTERS.
I THINK WE HAVE SENT SO MANY
SAMPLES TO THE NICHD BIOROOS POS
BIOREPOSITORY THAT THEY JUST
DIDN'T HAVE THE SPACE TO DO THAT
ANYMORE OR THE FUNDING SO RIGHT
NOW THEY'RE BEING STORED AT THE
INDIVIDUAL SITES.
SO CHALLENGES RELATED TO THAT IS
FREEZER SPACE AT THE CLINICAL
SITES DEPENDING ON WHAT THE SIZE
OF THOSE STUDIES ARE, BECAUSE
FREQUENTLY ON MFMU, WE'LL DO 5-,
10,000 SAMPLE SIZE STUDIES, AND
SO IF YOU'RE A BIG RECRUITER,
YOU'RE GOING TO HAVE A LOT OF
PATIENTS AND A LOT OF SAMPLES.
THE OTHER CHALLENGE IS THAT
FREEZERS AND STORAGE IS NOT
COVERED WITHIN ANY OF THE
EXISTING GRANT FUNDING, AND THEN
PLANNED BIOSPECIMEN ANALYSES
REQUIRE SHIPMENT FROM ALL THE
INDIVIDUAL SITES RATHER THAN
FROM A SINGLE CENTRAL REPOSITORY
WHICH DEFINITELY MAKES THE
PULLING OF SAMPLES TO RUN ASSAYS
MORE CHALLENGING.
SO THESE ARE JUST OUR TWO TRIALS
THAT ARE ONGOING WITH
BIOSPECIMENS.
SO I MENTIONED THIS ONE THAT'S
COLLECTING VAGINAL SWABS AND
THEN THE OTHER IS SERUM PLASMA
AND PLACENTA.
SO TO TALK A LITTLE BIT ABOUT
THE FUTURE, SO I THINK IN ONE OF
THE VERY BEGINNING TALKS, THEY
MENTIONED THE NEW PAR, SO THAT'S
PAR23-037.
I THINK THAT IS A NUMBER THAT I
WILL HAVE FOREVER ENGRAINED IN
MY MEMORY.
SO IN THAT, YOU NEED TO -- IN
GRANTS THAT ARE SUBMITTED
THROUGH THIS NEW MECHANISM TO
CONDUCT STUDIES WITHIN THE
NETWORKS, YOU HAVE TO INCLUDE
FUNDING FOR A BIOREPOSITORY.
AND SO BIOSPECIMENS ARE SENT TO
A BIOREPOSITORY THAT ARE
IDENTIFIED IN THAT GRANT
APPLICATION, AND WHAT WE HAVE
DONE THUS FAR, WHICH, YOU KNOW,
I THINK CAN BE DISCUSSED AND
RE-EVALUATED, IS USUALLY THE
LEAD CLINICAL CENTER WHO IS
SUBMITTING THAT GRANT WOULD
SERVE AS THE BIOREPOSITORY AND
THE SAMPLES WOULD BE SHIPPED
THERE.
HOWEVER, CHALLENGES TO THAT IS
THAT THERE'S NO FUNDING FOR THAT
STORAGE BEYOND THE FIVE-YEAR
LIFE OF THAT GRANT, SO YOU
SUBMIT THE GRANT WITH COSTS
COVERED FOR THE BIOREPOSITORY
BUT THEN WHAT HAPPENS AFTER FIVE
YEARS?
AND THEN THE OTHER POINT, TOO,
THAT I JUST WANTED TO RAISE IS
THAT ANY TIME THAT THERE'S
BUDGET CUTS TO THE GRANT, EITHER
BEFORE GRANT SUBMISSION OR AFTER
GRANT SUBMISSION, THE EASIEST
THING TO ELIMINATE OUT OF A
GRANT IS THE COLLECTION OF
BIOSPECIMENS.
IT'S THE EASIEST THING.
I KNOW WE PROBABLY -- MAYBE NOT
EVERYBODY AGREES BUT WHEN YOU'RE
TRYING TO MAKE A QUICK CUT TO A
BUDGET, THAT HAS BEEN THE FIRST
THING THAT WE'VE HAD TO CUT OUT
OF THERE, SO WE'VE EITHER HAD TO
COMPLETELY ELIMINATE THE
COLLECTION OF BIOSPECIMENS WITH
THE HOPE OF GETTING ANCILLARY
FUNDING TO COLLECT THOSE OR
WE'VE HAD TO REDUCE THE NUMBER
OF SAMPLES OR THE NUMBER OF
PATIENTS AND WHAT SAMPLES ARE
COLLECTED.
SO THIS IS OUR STUDY THAT IS IN
IMPLEMENTATION.
IT'S OUR VERY FIRST STUDY THAT'S
BEEN FUNDED UNDER THAT NEW PAR,
SO WE'RE VERY EXCITED ABOUT
THAT.
YOU CAN SEE -- AND I KNOW
SOMEONE MENTIONED EARLIER ABOUT
THE AZITHROMYCIN, SO WE'RE GOING
TO BE LOOKING AT ADJUNCTIVE
AZITHROMYCIN WITH THOSE WITH
SCHEDULED OR PRE-LABOR CESAREAN.
YOU'LL SEE WE ENDED UP HAVING TO
DROP THE COLLECTION OF
BIOSPECIMENS TO 1,000.
ALL THE DETAILS ON THE
BIOSPECIMENS ARE STILL BEING
WORKED OUT SO I DON'T HAVE ANY
DETAILS ON THOSE, AND THEN I
KNOW THERE'S THE INTENT TO GET
EXTERNAL FUNDING TO DO THE
MICROBIOME.
AND THAT'S ALL I HAVE.
I DON'T KNOW IF WE'RE DOING
QUESTIONS AFTER EACH ONE OR AT
THE END?
>> -- FUNDING BEYOND THE
FIVE-YEAR GRANT PERIOD?
>> ALL THE QUESTIONS WILL BE
ADDRESSED IN THE PANEL
DISCUSSION SECTION AT THE END OF
THE SECTION.
>> THANK YOU, DR. CLIFTON.
OUR NEXT TALK IS ON REPRODUCTIVE
RESEARCH BIOBANKING,
INFRASTRUCTURE AND ADAPTATIONS,
BY DR. ANTONIA FROLOVA.
FROM WASHINGTON UNIVERSITY.
>> HI, EVERYBODY.
MY NAME IS TONI FROLOVA.
I'M HERE FROM WASHINGTON
UNIVERSITY AS THEY MENTIONED.
LET'S SEE IF WE CAN GET THIS UP
AND RUNNING.
SO I'M GOING TO TALK A LITTLE
BIT ABOUT OUR BIOBANK, FORMERLY
KNOWN AS THE WIHSC, WE'RE DOING
SOME REBRANDING NOW.
I'LL TALK
ABOUT.
SO WE'LL TALK ABOUT THE HISTORY
AND THEN SOME CURRENT AND
ONGOING METRICS OF SUCCESS AS
WE'VE DEFINED THEM AND KIND OF
THINGS THAT WE'RE AIMING FOR.
SOME OF THESE HAVE ALSO BEEN
MENTIONED BY OTHER SPEAKERS
ALREADY.
SO THE WIHSC WAS ORIGINALLY
STARTED IN 2008 SO WE'RE ABOUT
15 TO 16 YEARS OLD AND THE
PURPOSE WAS TO CREATE JUST A
PROSPECTIVE COMPREHENSIVE BIOSES
MEN BANK OF TISSUES,
REPRODUCTIVE TISSUES FROM WOMEN
BEFORE PREGNANCY AND DURING
PREGNANCY.
IT WAS ORIGINALLY STARTED B IN E
REI SPACE SO YOU CAN SEE IT WAS
A LITTLE BIT HEAVY ON THE REI
SPECIMEN, SO FOLLICULAR FLUID
WAS INCLUDED, DISCARDED OOCYTES,
GRANULOIS A CELLS, CONTINUED TO
MATCH MATERNAL BLOOD, CORD
BLOOD, PLACENTA, AMNIOTIC FLUID
COLLECTED.
STARTING LAST YEAR AND REALLY
INTO THIS YEAR, WE'VE RENAMED OR
WORKING ON RENAMING THE BIOBANK
TO REPRODUCTIVE SPECIMEN
PROCESSING AND BANKING AND THIS
IS TO MAKE IT MORE INCLUSIVE
BECAUSE WE DO INCLUDE SOME MALE
SAMPLES THAT ARE REPRODUCTIVE
SAMPLES, SEMEN AND SPERM, AS
WELL AS IN ADDITION TO --
ACTUALLY INSTEAD OF JUST
BANKING, WE ARE FOCUSED A LITTLE
BIT MORE ON PROCESSING TISSUES
FOR VARIOUS STUDIES, AND THIS IS
OH MAKE THEM MORE USED BY OUR
RESEARCHERS, SO WE'RE TRYING TO
BE A LITTLE MORE INCLUSIVE IN
OUR TIE TILL.
BUT HISTORICALLY THIS IS WHAT'S
IN THE BANK NOW.
SO YOU CAN SEE ABOUT 64,000
SAMPLES, AND THIS IS FROM -- UP
TO ABOUT 3,000 PATIENTS FOR
MATERNAL BLOOD FOR EXAMPLE, BUT
THESE ARE ALL FROM VARIOUS
STUDIES AND VARIOUS POINTS IN
COLLECTION, SO REALLY DON'T HAVE
A NUMBER OF SUBJECTS THAT'S
EXACT BECAUSE SOME OF THESE ARE
PLACHED AND SOMATCHED AND SOME .
YOU CAN SEE THE NUMBERS DON'T
EQUAL SAMPLES BECAUSE MANY OF
THESE ARE CYRIL YA SERIALLY COL.
MANY OF THE PATIENTS WERE ASKED
TO DONATE BLOOD THROUGHOUT THEIR
PREGNANCY, SO THERE'S AT LEAST
THREE MATCHED SAMPLES FROM
FIRST, SECOND, THIRD TRIMESTER,
DEPENDING ON HOW THE STUDY WAS
ORGANIZED.
IN ADDITION TO THE SAMPLES, WE
HISTORICALLY HAVE COLLECTED
EXTENSIVE PATIENT CLINICAL DATA.
WE'VE TRIED TO KEEP THIS VERY
CONSISTENT BETWEEN STUDIES, SO
120 DATA POINTS ARE ALWAYS
COLLECTED FOR PATIENTS ENROLLED
IN RPR BANK, SO MATERNAL
DEMOGRAPHICS, MATERNAL CO-MORBID
ITS, PREGNANCY COMPLICATIONS,
DELIVERY INFORMATION AS WELL AS
NEONATAL OUTCOMES, ALL KEPT IN
THE REDCAP DATABASE, ENCRYPTED
AND SECURE.
IN ADDITION TO THE CLINICAL
DATA, THOUGH, I THINK IT'S
IMPORTANT TO POINT OUT WE'VE
ALWAYS KEPT SCREENING DATA AND
I'LL SHOW YOU WHY THAT BECOMES
IMPORTANT WITH A LITTLE CASE
STUDY.
THIS ALLOWS US TO REALLY KEEP
TRACK OF OUR POPULATION WHERE
SAMPLES ARE COMING FROM, AND
THEN IN ADDITION, SEE WHO'S
DECLINING RESEARCH AND WHO'S
CONSENTING FOR RESEARCH AND TO
SEE IF WE CAN REALLY HAVE SOME
EQUITY IN THE POPULATION AND IN
THE BANK.
WHO RUNS THIS?
SO THE INITIAL TEAM WAS A
DIRECTOR.
THIS HAS SWITCHED OVER THREE
TIMES, I BELIEVE, AND I'M THE
LATEST ONE.
AS SENIOR COORDINATOR, WE'VE
BEEN LUCKY ENOUGH TO HAVE THE
SAME SENIOR COORDINATOR FOR ALL
ACCEPT YEA16YEARS SO IT'S A G
HISTORICAL -- AS WELL, THEY'RE
ABLE TO KEEP UP WITH CONSENTS,
CLINICAL DATA EXTRACTION,
EXPLICOMPLIANCE AND ALSO TAKING
REQUESTS FOR PROSPECTIVE AND RE
FRO SPECULATIVE SAMPLES.
THEN A CLINICAL LAB SUPERVISOR
WHO'S IN CHARGE OF THE SAMPLE
PROCESSING TRACKING, PROTOCOL
CLIENS AND SOP DEVELOPMENT ALONG
WITH THE DIRECTOR AND SENIOR
COORDINATOR.
WE'VE ALSO HAD ADDITIONAL
PERSONNEL, THIS KIND OF VARIES
WITH STUDIES ONGOING AT THE
MOMENT.
SO LAB RESEARCH ASSISTANTS WHO
ARE THERE TO HELP WITH SAMPLE
PROCESSING.
SOME OF THE SAMPLE PROCESSING,
DEPENDING ON THE STUDY THAT'S
ENROLLED, CAN TAKE UP TO TWO
HOURS PER SAMPLE.
AND THEN CLINICAL RESEARCH
ASSISTANTS.
THIS, I THINK, IS ONE OF THE
MOST IMPORTANT ASPECTS OF OUR
STUDY, OF OUR BANK, IS THAT WE
HAVE CLINICAL RESEARCH
ASSISTANTS WHO ARE SPECIFICALLY
TRAINED TO CONSENT PATIENTS ON
LABOR AND DELIVERY.
AND YOU CAN IMAGINE THAT'S A
PRETTY SENSITIVE PLACE FOR
RESEARCHERS TO BE APPROACHING
PATIENTS, AND WE TAKE GREAT
PRIDE IN HAVING THESE
INDIVIDUALS AND THEIR SUCCESS
RATE WITH CONSENTS.
SO IF WE LOOK HISTORICALLY AT
WHAT THE BANK HAS BEEN THROUGH
SINCE 2008, THE GOAL WAS TO JUST
GET PROSPECTIVE UNIVERSAL
BANKING FOR WOMEN UNDERGOING --
DESIRING PREGNANCY AND IN
PREGNANCY, AND DURING THE FIVE
YEARS WHEN THE BANK WAS FIRST
STARTED, OVER 40,000 SAMPLES
WERE BANKED, BUT AS SOMEBODY
ELSE MENTIONED, THESE WERE LOW
RISK SAMPLES FOR THE MOST PART.
THE FUNDING CAME FROM A PRIVATE
GRANT, WHICH THEN RAN OUT AFTER
FIVE YEARS, SO THAT'S ANOTHER
CHALLENGE THAT I'LL TALK ABOUT.
SO IN 2013 WHEN WE LOOKED BACK
IN ALL OF THOSE SAMPLES BANKED,
THEY WEREN'T BEING UTILIZED THAT
MUCH BY OUR RESEARCHERS, SO WE
RESTRUCTURED TO BEGIN PARTNERING
WITH OTHER STUDIES, SO THIS IS
WHERE OUR GLOBAL CONSENT AND
DUAL ENROLLMENT CAME IN, SO WE
TRY TO REALLY UTILIZE ONE
SPECIMEN COLLECTION CONTROL --
CONSENT FORM FOR AS MANY STUDIES
AS POSSIBLE, SO IF THEY'RE JUST
MEETING SAMPLES, IT WILL GO
THROUGH THIS CONSENT.
AND THIS HAS SEVERAL BENEFITS.
IT ALLOWS US TO CONSTANTLY BE
UPDATING OUR PROTOCOLS FOR
SPECIFIC USES, THINGS THAT WERE
COLLECTED 15 YEARS AGO MIGHT NOT
BE COLLECTED IN A WAY THAT'S
USEFUL NOW, FOR EXAMPLE, THINGS
THAT WERE COLLECTED FOR
HISTOLOGY BACK THEN CAN'T BE
USED FOR RNA SEQ NOW.
SO THIS ALLOWS US TO REALLY
UPDATE FOR THE USES THAT ARE
BEING UTILIZED NOW.
IT ALSO MOST IMPORTANTLY, I
THINK, LIMITS APPROACH FOR
PATIENTS.
SO APPROACHING A PATIENT WITH
ONE CONSENT FORM AS OPPOSED TO
SIX OR SEVEN OR 10 IS MUCH MORE
PALATABLE TO OUR PATIENTS AND
OUR RESEARCH ASSISTANTS.
AND THIS REALLY HAS INCREASED
STUDY ENROLLMENT.
AND IN ADDITION, REALLY FOCUSING
THIS WAY ALLOWS FOR SAMPLES TO
BE BANKED THAT CAN BE USED BY
RESEARCHERS WHO CONDUCTED A
STUDY BUT THEN NEED TO DO SOME
SECONDARY ANALYSES, FOR EXAMPLE,
WITH THE SAME BACKGROUND, BUT
ALSO IT HAS SOME EXTRA SAMPLES
FOR ADDITIONAL STUDIES THAT COME
UP.
IN 2014 WE STOPPED ENROLLMENT
FOR JUST UNIVERSAL BANKING AND
HAVE ONLY BEEN USING DUAL
ENROLLMENT WITH OTHER STUDIES,
AND THEN IN 2015, WE RESTRUC
RESTRUCTURED BUSINESS -- AND
BECAME A RESEARCH CENTER TO TRY
TO STAY AFLOAT FINANCIALLY.
2017, WE PARTNERED WITH THE
MARCH OF DIMES COHORT STUDY.
YOU CAN JUST SEE THE NUMBER OF
SPECIMENS THAT INCREASED DURING
THE THREE YEARS THAT WE
PARTICIPATED IN THIS STUDY, AND
THEN IN 2021, WE'VE DEVELOPED
SOME NEW METRICS THAT WE'RE
GOING TO BE -- THAT I'LL TALK
ABOUT.
SO THE NEW METRICS, WE REALLY
ASKED OURSELVES WHAT DETERMINES
THE SUCCESS OF A TISSUE BANK A
COUPLE YEARS AGO, AND THESE ARE
THE THINGS THAT WE CAME UP WITH.
SO OBVIOUSLY SAMPLES COLLECTED,
PROCESSED AND BANKED.
YOU CAN LOOK AT THIS SEVERAL
WAYS.
SO ONE, JUST NUMBERS.
BUT TWO, REALLY QUALITY OF THE
SAMPLES, AND HOW THEY'RE BEING
COLLECTED.
I THINK THOSE ARE IMPORTANT
THINGS TO KEEP IN MIND.
THEN WE LOOK AT WHAT SAMPLES ARE
BEING REQUESTED ON A REGULAR
BASIS.
I'LL TALK ABOUT THAT.
AS WELL AS COST.
WE ALL KNOW IT COSTS A LOT TO
COLLECT AND STORE THE SAMPLES,
AND WHERE IS THAT FUNDING COMING
FROM.
AND HOW ARE WE DOING ON THE INS
AND OUTS.
AND THEN LAST BUT NOT LEAST, I
THINK ACADEMIC OUTPUTS ARE
REALLY IMPORTANT FOR US TO KEEP
TRACK, SO THAT MEANS
PUBLICATIONS FOR THE MOST PART.
WE HAVE NOT BEEN HISTORICALLY
GOOD AT KEEPING TRACK OF THAT
BUT ALSO COMMUNITY ENGAGEMENT IS
ANOTHER PIECE I'LL MENTION AT
THE END.
SO THIS IS KIND OF WHAT OUR
METRICS LOOK LIKE IN TERMS OF
SAMPLES COLLECTED.
SO YOU CAN SEE IN THE PURPLE,
THAT WAS THE PROSPECTIVE
COLLECTION AND THEN IN THE GREEN
IS WHEN WE DROPPED OFF AND BEGAN
JUST PARTNERING WITH STUDIES IN
THE DUAL ENROLLMENT.
2017 IS WHEN THE MARCH OF DIMES
COHORT HAPPENED.
YOU CAN SEE THERE WAS A BOLUS OF
SAMPLES, 2020 AND 2021 WAS OUR
COVID YEARS.
BUT WHILE WE DIDN'T BANK AS MANY
SAMPLES, WE ACTUALLY ENDED UP
PROCESSING QUITE A FEW FOR
PROSPECTIVE STUDIES, AND THESE
WERE PRIMARILY COVID SAMPLES AND
WERE UTILIZED RIGHT AWAY FOR
STUDIES AND I THINK THOSE ARE
IMPORTANT NUMBERS TO KEEP TRACK
FOR OURSELVES.
SO IN 2021, WE ALSO STARTED A
MONTHLY REVIEW OF ALL OF OUR
SCREENING AND CONSENT NUMBERS,
KEEPING TRACK OF GLOBAL AND
INDIVIDUAL STUDY CONSENTS AS
WELL AS WHAT WAS BEING PROCESSED
AND BANKED.
THIS IS WHAT THOSE NUMBERS LOOK
LIKE.
AND YOU CAN REALLY GET PRETTY
GRANULAR WITH WHAT'S COMING IN,
WHAT'S COMING OUT, WHAT'S
SUCCESSFUL.
I LIKE TO LOOK AT IT IN A YEAR
BY YEAR FASHION AND REALLY WHAT
I FOCUSED ON IS TRYING TO GET AS
MANY STUDIES OVER ON TO THE
WIHSC GLOBAL CONSENT IN ORDER TO
DECREASE THE BURDEN FOR OUR
PATIENTS, AND YOU CAN SEE WE'VE
BEEN PRETTY SUCCESSFUL IN DOING
THAT.
AND I THINK THAT'S EVEN BETTER
SEEN HERE WHEN WE LOOK AT THE
STUDIES SUPPORTED.
SO WE'RE SUPPORTING RIGHT NOW
CURRENTLY 17 STUDIES, SIX OF
THEM ARE GOING IN UNDER ONE
CONSENT AND YOU CAN IMAGINE THAT
THAT'S MUCH EASIER TO GET A
GREATER NUMBER OF PATIENTS AND
SAMPLES COLLECTED.
WE LOOK AT RECRUITMENT ON A
MONTHLY BASIS.
THIS IS JUST AN EXAMPLE OF WHAT
THAT LOOKS LIKE, WHO'S BEING
SCREENED, WHO'S BEING
APPROACHED, WHO'S BEING
CONSENTED AND WHAT'S BEING
COLLECTED.
I THINK THIS IS REALLY IMPORTANT
BECAUSE WHEN WE LOOK BACK AT
SOME POINT AT OUR NUMBERS, FOR
EXAMPLE, WE HAD ONLY 25% OF THE
SAMPLES COMING IN WERE FROM OUR
BLACK PATIENTS, BUT WE KNOW THAT
OUR LND POPULATION IS ABOUT 50%
BLACK SO WE WERE ABLE TO GO BACK
AND REALLY TRY TO FIGURE OUT
WHERE WE WERE LOSING SOME OF
THIS DIVERSITY.
WE WERE HAPPY TO FIND THAT WE
WERE NOT APPROACHING PATIENTS --
BUT WE DID HAVE QUITE A
STAGGERING DIFFERENCE IN THE
CONSENT THAT WAS BEING DIFFERENT
SO OUR BLACK PATIENTS ARE ONLY
ABOUT 30% OF THE TIME CONSENTING
TO TISSUE COLLECTION AND
BIOBANKING AS OPPOSED TO OUR
WHITE PATIENTS.
WHEN WE LOOKED EVEN CLOSER AT
THAT, IT WAS SPECIFICALLY
DECLINED -- THEY WERE DECLINING
SPECIFICALLY BASED ON SAMPLE
COLLECTION AND PLACENTA
COLLECTION SPECIFICALLY.
SO THAT'S SOMETHING WE'RE GOING
TO BE GOING BACK AND LOOKING
INTO EVEN MORE TO TRY TO FIGURE
OUT HOW WE CAN EVEN THAT PLAYING
FIELD A LITTLE BIT.
AND I'LL TALK ABOUT THAT A
LITTLE BIT MORE WITH MY
COMMUNITY ENGAGEMENT PIECE.
ANOTHER METRIC TO LOOK AT IS
REQUESTS.
THIS IS AN EXAMPLE OF WHAT OUR
RETROSPECTIVE SAMPLE
DISTRIBUTION LOOKS LIKE, BUT WE
HAVE THE SAME METRICS FOR
PROSPECTIVE SAMPLE COLLECTION,
AND SOME OF THOSE GET BANKED, SO
RETROSPECTIVELY, WE CONSISTENTLY
GET ABOUT FIVE TO 10 STUDIES A
YEAR REQUESTING SAMPLES, AND YOU
CAN SEE THOSE CAN BE INTERNAL
AND EXTERNAL, HISTORICALLY MOST
REQUESTED SAMPLE TYPES ARE
PLACENTA, CORD BLOOD AND
MATERNAL BLOOD AND THAT'S WHAT
WE CONTINUE TO TRY TO BANK THE
MOST AS WELL WHEN WE DO THINGS
PROSPECTIVELY.
THIS ALSO HELPS US DETERMINE
WHAT KIND OF SAMPLE PROCESSING
IS BEST, SO IF SAMPLES ARE BEING
REQUESTED BUT WE DON'T HAVE THE
ADEQUATE PROCESSING, WE CAN
REALLY ADJUST GOING FORWARD.
AND THIS BRINGS ME TO ANOTHER
METRIC WHICH IS QUALITY
ASSURANCE.
SO I THINK IT'S REALLY IMPORTANT
FOR ANY NEW PROSPECTIVE OR
RETROSPECTIVE REQUEST VIEWED BY
THE PI DOING THE REQUEST AS WELL
AS THE DIRECTOR AND FETAL
PROCESSING THE SAMPLES, I WANT
TO MAKE SURE THAT OUR SAMPLES
CAN ANSWER THE QUESTIONS THAT
ARE BEING ASKED BY THE
RESEARCHERS OUT THERE.
AND NOT HAND OUT SAMPLES THAT
AREN'T BEING UTILIZED OR
ANSWERING QUESTIONS CORRECTLY IN
THE END.
TO THIS, WE ALSO DO A LIT REVIEW
ONCE A YEAR TO MAKE SURE THAT
OUR SOPs ARE UP TO DATE.
IN TERMS OF COST, PERSONNEL IS
THE BIGGEST COST AS WE ALL KNOW,
BUT I THINK THE STORAGE QUESTION
IS A BIG ONE IN TERMS OF ON-SITE
VERSUS OFF SITE.
ALL OF OUR SAMPLES USED TO BE
STORED OFF SITE AND THAT BECAME
COST PROHIBITIVE AT SOME POINT
SO WE STARTED SHIFTING OVER TO
ON SITE AND THIS YEAR ALL OF THE
SAMPLES WILL BE TRANSFERRED BACK
TO BE ON SITE WHICH HAS ACTUALLY
NOW TURNED OUT TO BE MORE
FINANCIALLY FEASIBLE THAN
PREVIOUSLY, SO THIS IS JUST A
PIECE THAT NEEDS TO BE I THINK
READDRESSED ON A REGULAR BASIS
BECAUSE THE PROS AND CONS CHANGE
OVER TIME.
AND AGAIN, SOMEBODY MENTIONED
THIS AS WELL, THE GRANT FUNDING,
SO INITIALLY THE WIHSC WAS GRANT
AND DEPARTMENT FUNDED AND IN THE
LONG RUN, THAT REALLY WASN'T
SUSTAINABLE, SO WE'VE SWITCHED
OVER TO A RECHARGE CENTER
BUSINESS MODEL, SO THIS IS A
UNIVERSITY UNIT THAT PROVIDES
PRODUCTS AND SERVICES FOR A FEE.
THE FEES HAVE TO BE VERY
STRICTLY CALCULATED BASED ON
PERSONNEL AND PROCESSING TIME
AND COST PER SAMPLE SO THIS IS
CONSTANTLY BEING RE-EVALUATED ON
AN ANNUAL BASIS BY OUR LAB
DIRECTOR AND OUR DIVISION OF
CLINICAL RESEARCH MANAGER.
WE HAVE TO COMPLY WITH SEVERAL
FEDERAL REGULATIONS AND INTERNAL
AND EXTERNAL AUDITS TO MAKE THIS
FEASIBLE, BUT IT'S BEEN A
MUCH -- MORE SUSTAINABLE
RESOURCE AS A RESULT, ALTHOUGH
STILL BEING SOMEWHAT
DEPARTMENT-FUNDED.
THEN ACADEMIC OUTPUT, I THINK
IT'S IMPORTANT TO REALLY KEEP
TRACK OF THE STUDIES THAT WE'RE
SUPPORTING BOTH PROSPECTIVE AND
RETROSPECTIVE IN THE
PUBLICATIONS COMING OUT.
IN THE LAST FOUR YEARS WE
STARTED KEEPING BETTER TRACK, UP
TO 25 STUDIES A YEAR ARE BEING
SUPPORTED BY THE BIOBANK AND
THESE ARE JUST THE PR PROSPECTI,
AND AN ADDITIONAL FIVE TO 10
RETROSPECTIVE STUDIES ARE
USUALLY BEING SUPPORTED.
THEN FINALLY AS I MENTIONED, I
THINK IT'S IMPORTANT TO REALLY
HAVE SOME COMMUNITY ENGAGEMENT
AND DISSEMINATE THE RESEARCH
FINDINGS TO OUR PARTICIPANTS AND
COMMUNITY.
THIS IS REALLY GOING TO MAKE OUR
PARTICIPANT RESEARCH MORE
INFORMED AND SAFE, AND IT'S
GOING TO GAIN TRUST AND
ENGAGEMENT FROM PATIENTS AND SO
THE WAY WE'RE DOING THAT IS
WE'RE ADDING A PORTION OF OUR
WEBSITE IN ORDER TO HAVE A LIST
OF ACTIVE STUDIES, PAST STUDIES,
AND MAKE THESE A LITTLE MORE
ACCESSIBLE TO THE LAY PUBLIC
AND, THEREFORE, OUR RESEARCH
ASSISTANTS WHEN APPROACHING
PATIENTS FOR ENROLLMENT CAN HAND
OUT THE WEBSITE AND HAVE THEM
READ ABOUT WHAT KIND OF RESEARCH
THEIR SAMPLES WILL BE USED FOR.
THESE ARE ALL OF OUR BIG PLAYERS
IN THE RESEARCH BANK RIGHT NOW,
AND I'LL TAKE ANY QUESTIONS.
I GUESS LATER, WE'LL DO
QUESTIONS.
>> THANK YOU, NEXT IS
CONSIDERATIONS FOR PLANNING A
BIOREPOSITORY, VICTORIA BLANC,
FROM UNIVERSITY OF MICHIGAN.
>> THANKS FOR PROVIDING ME TO
TELL BUT SOME CONSIDERATIONS AS
YOU PLAN YOUR BIOREPOSITORY.
I'M AT THE UNIVERSITY OF
MICHIGAN MEDICAL SCHOOL, WHERE
WE HAVE A CENTRAL BIOREPOSITORY
WHICH WAS STARTED IN 2013 WITH
MY HIRE, WE HAVE A MISSION TO
FACILITATE HEALTHCARE, BETTER
HEALTHCARE OUTCOMES BY PROVIDING
HIGH QUALITY, HIGHLY ANNOTATED
BIOSPECIMENS DONATED FOR
CLINICAL AND TRANSLATIONAL
RESEARCH.
IT'S IMPORTANT TO NOTE THAT THE
SPECIMENS ARE DONATED.
WE TAKE OUR PARTICIPANTS'
CONTRIBUTIONS VERY SERIOUSLY,
AND SO WE MAKE SURE THAT WE ARE
GOOD STEWARDS OF THAT VERY
PRECIOUS RESOURCE.
WHAT WE DO AT THE CENTRAL
BIOREPOSITORY AS A BIOREPOSITORY
OF COURSE WE PROVIDE BIOSTORAGE,
WE PROVIDE A SAFE ENVIRONMENT,
WE MAKE SURE THAT OUR FREEZERS
ARE WELL MAINTAINED AND
CONNECTED TO BACKUP POWERS,
CONNECTION TO OUR ELECTRONIC
HEALTH RECORDS, A RESEARCH DATA
WAREHOUSE AND OTHER DATABASES
LIKE REDCAP.
OUR SPECIMENS ARE TRACKED IN OUR
OWN DATABASE ALONG WITH THOSE
OTHERS.
WE PROVIDE A STANDARDIZED BROAD
CONSENT WHICH IS IMPORTANT FOR
FUTURE UNSPECIFIED RESEARCH.
THIS IS NOT THE BIG B BROAD
CONSENT FROM THE REGULATORY
AGENCY, THIS IS A BROAD CONSENT
FOR BIOBANKING.
IT DOES ALLOW ALL SORTS OF USES,
WE KIND OF MAKE IT AS UP FRONT
AS POSSIBLE THAT SAMPLES WILL BE
USED FOR ANYTHING.
WE PROVIDE INFRASTRUCTURE FOR
GOVERNANCE AND COMPLIANCE WITH
THE REGULATIONS AND IMPORTANTLY
WE PROVIDE PROCESSES FOR SAMPLE
SHARING.
IN TERMS OF SPECIMEN ACCESS, WE
PROVIDE LARGE NUMBERS OF SAMPLES
READILY AVAILABLE TO OUR
RESEARCHERS, ALONG WITH DEEP
CLINICAL AND PHENOTYPE DATA AND
THAT'S BECAUSE OF THE CONNECTION
TO THE ELECTRONIC HEALTH RECORDS
BUT ALSO THROUGH THINGS LIKE
REDCAP.
THE EHR ALLOWS US TO HAVE
LONGITUDAL AND OUTCOMES DATA
CONNECTED TO THE BIOSPECIMENS
WHICH IN TURN TOGETHER SHOULD
PRODUCE FASTER PUBLICATIONS FOR
OUR INVESTIGATORS.
IN TERMS OF THE RESEARCH
ENTERPRISE, WE PROVIDE AN
ECONOMY OF SCALE BECAUSE WE ARE
A CENTRALIZED BIOREPOSITORY.
WE'RE NOT MAKING INDIVIDUAL
INVESTIGATORS HAVE THEIR OWN
FREEZERS AND RECAPITULATING
EFFORTS OVER AND OVER AGAIN.
ENHANCED COMPLIANCE IS CRITICAL,
EVERYTHING GOES THROUGH ONE DOOR
WHILE WE MAKE SURE THAT OUR
INVESTIGATORS ARE KEEPING TRACK
OF THINGS THE WAY THEY'RE
SUPPOSED TO.
HAVING A CENTRAL BIOREPOSITORY
MAKES US A LITTLE MORE
COMPETITIVE FOR GRANTS WE
BELIEVE SO WE'RE ABLE TO PROVIDE
THAT ECONOMY TO THE SCHOOL AND
THE UNIVERSITY.
AND BECAUSE WE ARE A CENTRAL
CORE FACILITY WE ALSO INTERACT
WITH OUR OTHER CORES VERY
EASILY.
SO WE PROVIDE SECURITY, QUALITY
ACCESS, EXPERIMENTAL POWER, RICH
DATASETS, AND ECONOMY.
SO ALL OF THAT IS COVERED BY A
GOVERNANCE STRUCTURE.
AS YOU CAN SEE HERE, THIS IS A
THEORETICAL FRAMEWORK, THIS IS
NOT OUR EXACT FRAMEWORK, THIS IS
FOR ALL OF YOU AT NICHD WHO ARE
THINKING ABOUT CREATING A
BIOREPOSITORY, HAVING A STEERING
COMMITTEE WHO DECIDES POLICY AND
GUIDANCE THAT ARE USED FOR THE
RUNNING OF THE BIOREPOSITORY,
PROVIDING SCIENTIFIC REVIEW AND
DETERMINATIONS ON ACCESS
REQUESTS, ARE THESE REQUESTS
REASONABLE, ARE THEY
SCIENTIFICALLY VALID, ARE THEY A
GOOD USE OF THE SPECIMENS.
STEERING COMMITTEE ALSO PROVIDES
BIOREPOSITORY PROGRAM ASSESSMENT
AND ADVISING, SO ALL OF THOSE
METRICS THAT YOU HEARD FROM THE
PREVIOUS TALK WOULD BE ASSESSED
DURING A STEERING COMMITTEE
MEETING AND TWEAKS COULD BE MADE
BASED ON RIMTIONS RECOMMENDATIM
THE EXPERTS IN THE OVERSIGHT
COMMITTEE.
SO THE STEERING COMMITTEE
REPRESENTS STAKEHOLDERS AT LARGE
SO THE UNIVERSITY OR THE NIH OR
WHOEVER ELSE IS A FUNDING AGENCY
PERHAPS BUT IT COULD ALSO
INCLUDE COMMUNITY MEMBERS AND
PATIENTS AND THIS WAY YOU GET
THE ENGAGEMENT YOU'RE SEEKING
FROM YOUR PARTICIPANTS.
DOWN BELOW I TALK ABOUT SOME OF
THE THINGS THAT THE PROGRAM
STEWARDSHIP AND OVER SIGHT CAN
LOOK AT.
AS I MENTIONED THE ACCESS
UTILIZATION REQUESTS, ARE THEY
SCIENTIFICALLY VALID, DO THEY --
ARE THEY FEASIBLE, CAN YOU
ACTUALLY DO THE EXPERIMENT
THAT'S PROPOSED.
AND THEN ALSO THE KPIs AND
METRICS.
I PUT DOWN USAGE AND APPROPRIATE
USE TO MAKE SURE THE SAMPLES ARE
BEING USED FOR A GOOD REASON OR
SCIENTIFICALLY VALID REASON BUT
ALSO THAT THEY ARE BEING USED.
ONE OF THE BIGGEST HURDLES TO A
SUCCESSFUL BIOBANK IS THE LACK
OF USE OF THE SPECIMENS.
THERE'S SO MANY SPECIMENS
SITTING IN FREEZERS, AS WE'VE
HEARD FROM PREVIOUS TALKS THIS
MORNING, AND WE WANT TO MAKE
SURE THAT THOSE SAMPLES GET
OUTDOOROUTTHE DOOR SO THEY CAN O
WHAT THEY'RE SUPPOSED TO DO.
POLICIES DELIVERED AS PART OF
THE STEERING COMMITTEE AND
OVERSIGHT COMMITTEE, IF YOU'RE
LOOKING TO RETURN RESULTS,
YOU'LL WANT TO HAVE A POLICY
ABOUT THAT.
IF YOU'RE LOOKING TO SHARE DATA,
YOU'LL WANT TO HAVE A POLICY
ABOUT DATA USE AGREEMENTS.
PUBLICATIONS, AUTHORSHIP, ALL OF
THESE THINGS ARE IMPORTANT TO
HAVE WRITTEN DOWN A PRIORI.
IT DOESN'T MEAN THEY CAN'T
CHANGE, BUT YOU S SHOULD HAVE SE
IDEA OF WHAT YOU WANT TO DO.
SO IN TERMS OF WHAT THE CBR DOES
AND HOLDS AT THE UNIVERSITY OF
MICHIGAN MEDICAL SCHOOL, WE ARE
A -- I GUESS A DISEASE OR
THERAPEUTIC AREA AGNOSTIC
BIOREPOSITORY.
WE SUPPORT ALL OF OUR
INVESTIGATORS.
WE ALSO SUPPORT INVESTIGATOR
COLLABORATIONS, SO WE HAVE FOUR
STUDIES THAT ARE MULTISITE, ONE
OF WHICH IS WITH THE NIDDK
CALLED THE KIDNEY PRECISION
MEDICINE PROJECT, WHICH IS A
GIGANTIC STUDY SO IF YOU'RE
INTERESTED IN ALL SORTS OF
PROCEDURES AND POLICY, I DO
RECOMMEND CHECKING OUT WHAT
THEY'RE DOING.
YOU CAN SEE THAT WE HAVE OVER
786,000 SAMPLES, AND THIS IS
FROM ABOUT 140,000 PARTICIPANTS.
THAT NIDDK STUDIES, WE HAVE A
LOT OF URINE, AS YOU CAN SEE IN
THE ORANGE PIE PIECE TO THE
RIGHT.
SO THAT DOES CONTRIBUTE TO THE
LARGE NUMBER OF BIOSPECIMENS.
IT'S A PRETTY EASY SAMPLE TO
GET.
YOU'LL ALSO SEE THAT WE HAVE A
FAIR AMOUNT OF PLASMA AND SERUM
AND A VARIETY OF OTHER SAMPLE
TYPES LISTED BELOW AND IN
SMALLER SLIVERS ON THE PIE
CHART.
WE ALSO KEEP A LARGE COLLECTION
OF DNA SAMPLES.
THIS IS A DNA SET FROM OUR
PATIENTS WHO HAVE HAD GENOTYPING
SO WE HAVE ABOUT 100,000
PATIENTS WITH BROAD GENOTYPE
DATA AVAILABLE.
IN TERMS OF PHYSICAL
INFRASTRUCTURE YOU NEED, WH WHAS
YOUR FOOTPRINT GOING TO LOOK
LIKE, WHAT KIND OF FREEZERS DO
YOU NEED, DO YOU NEED LN2 VAPOR,
LN2 LIQUID, THOSE KINDS OF
THINGS.
WHAT OTHER ENVIRONMENTS ARE YOU
LOOKING TO STORE SAMPLES IN,
ROOM TEMPERATURE, HUMIDITY
CONTROL, MAKE SURE THAT THEY DO
NOT GET MOLDY BASICALLY.
ALL THOSE MINUS 80s THAT YOU
SEE LINED UP, THEY GET HOT, SO
YOU NEED TO HAVE A VERY GOOD
HVAC SYSTEM IN YOUR
INFRASTRUCTURE, KEEP IT COOL.
AND YOU'LL ALSO NEED BACKUP
POWER FOR THOSE FREEZERS, OR
BACKUP COOLING, OR BOTH.
SO ON THE LOWER RIGHT PANEL, YOU
CAN SEE THOSE ARE CARBON DIOXIDE
CYLINDERS.
THOSE ARE CONNECTED TO ALL OF
OUR MINUS 80 FREEZERS, SO IN THE
EVENT OF A PROLONGED POWER
OUTAGE OR A COMPRESSOR FAILURE,
THE CO2 WILL KICK IN AND KEEP
THE SAMPLES COLD.
WE ALSO HAVE TWO GENERATOR
SYSTEMS AT THE UNIVERSITY OF
MICHIGAN TO KEEP OUR POWER
SUPPLY ON.
THEN IF YOU HAVE LN2 OR IF YOU
HAVE CARBON DIOXIDE, YOU'RE
GOING TO WANT TO MAKE SURE THAT
YOU'RE MEASURING THE OXYGEN SO
THAT PEOPLE DON'T ASPHYXIATE
WHILE THEY'RE WORKING.
WE'VE ACTUALLY HAD TO CREATE
SCAVENGER EVENTS TO MAKE SURE
THE LN2 AS IT'S FILLING OUR
LN2 TANKS DON'T PRODUCE SO MUCH
VAPOR THAT YOU CAN'T HAVE A SAFE
WORKING ENVIRONMENT.
SO OUR INFRASTRUCTURE IS 2800
SQUARE FOOT OF STORAGE.
WE HAVE CURRENTLY 14 LARGE
CRYOGENIC FREEZERS WITH SPACE
FOR 25.
WE HAVE 18 MINUS 80 FREEZERS
WITH SPACE FOR 27.
WE ALSO STORE SAMPLES AT MINUS
24 DEGREES AND AMBIENT.
WE DO HAVE A BULK TANK -- SO OUR
NITROGEN CRYOGENIC TANKS ARE
CONNECTED TO A BULK TANK OUTSIDE
THE BUILDING, AND THE TANKS
AUTOMATICALLY CALL FOR LN2 AS
NEEDED.
AS I MENTIONED WE HAVE MULTIPLE
REDUNDANT BACKUP POWER SOURCES.
WE HAVE A CO2 BACKUP ON OUR
MECHANICALS, WE ALSO HAVE
24/7 TEMPERATURE MONITORING AND
ALARMS.
JUST TO HIGHLIGHT, WE ALSO HAVE
A LABORATORY WITH 2200 SQUARE
FOOT OF AUTOMATED TECHNOLOGIES
AND LAB BENCHES.
THIS IS BECAUSE WE DO A FAIR
AMOUNT OF PROCESSING OF
BIOSPECIMENS ON SITE, SO WE DO
DNA ISOLATION, PBMC ISOLATIONS
AND NOW WE'RE STARTING TO DO
SOME DNA FROM PLASMA.
SO CIRCULATING DNA.
SO WHEN IS YOUR FREEZER GOING TO
FAIL?
IT'S GOING TO FAIL IN THE MIDDLE
OF THE NIGHT.
THERE'S ABOUT 8600, 8700 HOURS
THAT YOU'RE THERE -- OR IN A
YEAR, AND 2,080, ABOUT, WHERE
PEOPLE ARE PRESENT IN A NORMAL
40-HOUR WORK WEEK.
SO THAT MEANS THAT 75% OF THE
TIME, YOUR FREEZERS ARE BEING
ACTIVE OUT OF HOURS.
SO WHAT ARE YOU GOING TO DO?
HOW WILL YOU KNOW THAT YOUR
FREEZER IS FAILING IF IT'S
SATURDAY AT 3:00 IN THE MORNING?
SO YOU NEED TO HAVE THAT
24/7 MONITORING CALL-OUT ALARM.
CALL-OUT MEANS IT'S SAYING HERE
I AM, COME GET ME, I'M OUT OF
RANGE.
AND YOU HAVE ASSIGNED ON-CALL
STAFF.
SO THIS IS CRITICAL THAT YOU
HAVE PEOPLE THAT ARE GOING TO BE
AWAKE -- OR NOT AWAKE, GOING TO
BE WAKENED BY THE ALARM THAT
COMES THROUGH THEIR BEEPER OR
THEIR PHONE.
AND WHAT WILL YOU DO WHEN YOUR
FREEZER FAILS?
IT'S 3:00 IN THE MORNING.
YOU STUMBLE OUT OF BED, DRIVE TO
WORK, YOU MUST HAVE A WRITTEN
PLAN.
YOU MUST KNOW WHAT YOU HAVE TO
DO.
THIS IS ABSOLUTELY REQUIRED.
AND YOU MUST HAVE A PLACE TO PUT
THE SAMPLES.
YOU CAN'T DO ANYTHING IF YOU
DON'T HAVE A PLACE TO PUT THE
SAMPLES AND YOU DON'T WANT TO BE
FINDING EMPTY HOLES IN THE
MIDDLE OF THE NIGHT.
SO HERE'S A PRO TIP, KEEP ONE
COLD EMPTY UNIT FOR EVERY 10
UNITS HOLDING INVENTORY.
SO YOU'RE GOING TO HAVE EMPTY
SPACE.
IT'S PART OF A BIOREPOSITORY.
-- EMERGENCY RESPONSES.
DO YOU WANT HAVE TO GO THROUGH
AND PHYSICALLY PRACTICE IT, CAN
YOU DO A TABLETOP EXERCISE.
MY TEAM AND I JUST DID A
TABLETOP EXERCISE LAST WEEK,
WHERE WE ENVISIONED A FLOOD AND
WE FOUND HOLES IN OUR DISASTER
RECOVERY PLAN.
WE DIDN'T EXPECT TO ACTUALLY
HAVE TO TURN OFF POWER WHEN THE
FIRST RESPONDERS WERE COMING IN
TO DRAIN THE WATER THAT HAD
ACCUMULATED ON THE FLOOR.
NOW AGAIN, THIS IS A THEORETICAL
EXERCISE, THIS WASN'T A REAL
EXERCISE.
SO WE WOUND UP SAYING OKAY, WHAT
IS OUR ABSOLUTE TIME LIMIT
BEFORE WE HAVE TO CALL IN THE
PROS TO COME AND GET THE SAMPLES
SO THAT WE DON'T LOSE THEM?
WE HAVE 780,000 SAMPLES.
I DON'T WANT TO LOSE THEM.
THE OTHER THING, MAINTAIN AND
TEST EQUIPMENT, YOU NEED TO DO
PREVENTIVE AND OPERATIONAL
MAINTENANCE REGULARLY.
GET IN CONTRACT WITH YOUR
VENDOR, DO IT YOURSELF, WRITE IT
DOWN.
MAKE SURE THAT YOU KEEP RECORDS
OF EVERYTHING THAT YOU DO.
HAVE A WRITTEN PROCEDURE FOR
WHAT YOU'RE GOING TO DO.
YOU NEED TO CALIBRATE, YOU NEED
TO CLEAN, YOU NEED TO TEST YOUR
ALARMS, YOU NEED TO TEST YOUR
ALARMS MORE THAN ONCE A YEAR.
YOU NEED TO TEST YOUR ALARMS
FREQUENTLY.
MAP YOUR FREEZERS SO YOU KNOW
WHERE YOU HAVE COLD SPOTS, WHERE
YOU HAVE WARM SPOTS, IF YOU'RE
FREEZER IS OPERATING
APPROPRIATELY.
TRACK YOUR LN2 USE IN YOUR
TANKS.
IF YOUR TANK HAS A LEAK, YOU'RE
GOING TO GO THROUGH A LOT MORE
LN2.
YOU WON'T NECESSARILY SEE IT
BECAUSE IT'S HAPPENING -- IT'S A
PINPOINT, BUT YOU WILL GO
THROUGH MORE LN2 SO YOU NEED TO
TRACK THAT AS WELL.
SO IT'S A PAIN BUT YOU HAVE TO
DO IT, KEEP THE RECORDS.
WE'VE ALL SEEN FREEZERS THAT
LOOK LIKE THIS.
HOPEFULLY NOT ANYONE HERE.
BUT I KNOW THAT IN MANY LABS
AROUND THE COUNTRY, FREEZERS
LOOK LIKE THIS.
HOW DO YOU KNOW WHERE YOUR
THINGS ARE?
TRACK IT IN ECK SE. I KNOW WHERE
EVERYTHING IS, I KNOW WHAT THE
FREEZER BOX IS, I KNOW WHAT'S
GOING ON.
NO, YOU DON'T.
DON'T DO THAT.
DON'T USE EXCEL.
DON'T DO THIS.
DON'T BE THIS LAB.
BE THIS LAB.
SO HAVE AN INFORMATION
MANAGEMENT SYSTEM WHERE YOU HAVE
FREEZER LOCATION MANAGEMENT,
FREEZER NUMBER, NAME, YOU HAVE
ITS SHELF, RACK, BOX, AND BOX
COORDINATES.
EVERYTHING IS TRACKED DOWN TO
THE POINT.
SO THAT YOU CAN ALWAYS FIND YOUR
SAMPLE, YOU ALWAYS KNOW WHERE
THEY ARE, IF ANYBODY ASKS YOU TO
PULL SAMPLE NUMBER 1234, CAN YOU
GO IN AND PULL SAMPLE NUMBER
1234.
BUT THAT'S NOT ALL THE
INFORMATION MANAGEMENT SYSTEM
DOES.
LIKE I SAID, IT DOES THE FREEZER
LOCATION MANAGEMENT, BUT IT CAN
ALSO KEEP TRACK OF YOUR
COLLECTION SITE, YOUR STUDY
PARTICIPANT AND SAMPLE LINKAGE,
WHICH IS OBVIOUSLY CRITICAL.
THE LIFECYCLE OF THE SAMPLE, THE
LINEAGE, WHO'S TOUCHED IT, WHERE
IT'S BEEN, WHAT'S BEEN PROCESSED
ON IT, WHAT ARE ITS DERIVATIVES?
WHERE IS IT IN THE FREEZER?
HOW HAS IT BEEN DISTRIBUTED?
HAVE YOU AUTO -- OR DISTRIBUTED
THE WHOLE THING?
IT ALSO CAN PROVIDE SPACE FOR
PREANALYTIC ANNOTATION, SO HOW
LONG DID THIS SAMPLE SIT ON THE
BENCH, WHAT WAS THE SPIN TIME,
WHAT WAS THE SPIN TEMPERATURE,
THOSE KINDS OF THINGS.
SO YOU CAN PROVIDE QC, THAT'S A
QC PIECE OF INFORMATION, YOU CAN
ALSO PROVIDE TEST RESULTS.
SO WE DO A LOT OF DNA ISOLATION.
WE TRACK HOW MUCH DNA WE GET, WE
TRACK THE CONCENTRATION, WE
TRACK THE YIELD, ALL OF THAT
KIND OF INFORMATION.
GENOTYPING SAMPLE STUDY, WE
TRACK THE QUALITY CONTROL OF THE
GENOTYPE TEST ITSELF.
SO WAS THERE CONTAMINATION, HOW
MUCH WAS THERE, DID IT PASS QC,
ET CETERA.
AND THEN YOU CAN ALSO LINK TO
OTHER DATA SYSTEMS.
OUR INFORMATION MANAGEMENT
SYSTEM LINKS DIRECTLY TO OUR EHR
FOR A VERY SMALL PROPORTION OF
INFORMATION.
WE HAVE THE MRN, WE HAVE THE
PATIENT DEMOGRAPHICS, AND THAT'S
IT.
IT IS PHI-COMPLIANT, SO WE ARE
ALL OKAY THERE.
ON THE RIGHT-HAND SIDE, YOU SEE
SORT OF A SAMPLE WORKFLOW OF
INFORMATION THAT'S BEING
COLLECTED.
YOU CAN HAVE -- IN OUR SYSTEM,
THERE'S A SUBJECT ID WHICH IS
THE SAME PERSON OVER AND OVER
AGAIN.
THAT PERSON CAN BE IN STUDY A
AND STUDY B WITH TWO DIFFERENT
IDENTIFIERS.
ALL OF THE SAMPLES FROM STUDY A
WILL BE COULD FLECTED TO THAT
PERSON, ALL THE SAMPLE FROM
STUDY B WILL BE LINKED TO THAT
PERSON BUT ALL LINKED UP TOP TO
THE SAME SUBJECT ID.
FOR PREGNANCY BIOREPOSITORY, YOU
SHOULD PROBABLY CONSIDER
CONFIGURING YOUR DATA SYSTEM
WITH A FAMILY ID, ESPECIALLY IF
YOU'RE TRACKING SPECIMENS FROM
MAMA AND BABY.
THIS IS JUST A QUICK OVERVIEW OF
BIOBANK PERSONNEL ROLES.
THESE ARE SORT OF BASIC
PERSONNEL ROLES.
A P.I. WHO'S GOING TO BE THE
OWNER OF THE SPECIMEN COLLECTION
AND RESPONSIBLE FOR THE
REGULATORY COMPLIANCE.
CRC WHO'S GOING ON OUT THERE
DOING THE CONSENTING AND DATA
MANAGER WHO'S GOING TO BE
ENACTING THE DATA POLICIES,
CREATING SECURE PROCEDURES AND
COMPLIANCE.
A LAB TECH TO MAKE KITS, PROCESS
SAMPLES, ET CETERA.
A PROJECT MANAGER AND A
LOGISTICS TECHNICIAN.
THESE ARE IDEAS, THESE ARE NOT
WRITTEN IN STONE.
YOU DO HAVE TO HAVE A P.I.
ALWAYS, BUT OTHERWISE, YOU
CAN -- THESE ARE FOR YOU TO
THINK ABOUT US A PLAN YOUR
BIOREPOSITORY.
MATERIALS THAT ARE NEEDED.
YOU NEED A PROTOCOL, WHAT'S
GOING TO HAPPEN IN THE CLINIC,
WHAT'S GOING TO HAPPEN AS YOU
PROCESS SAMPLES.
THIS IS THE THING THAT IS
APPROVED BY THE IRB.
THE MANUAL OF OPERATION, THIS IS
SORT OF A -- IT'S A MANUAL,
RIGHT?
WHAT'S GOING TO HAPPEN.
HOW DO WE DO THE PARTICIPANT
SCREENING, HOW DO WE DO THE
CONSENTING, THAT KIND OF THING.
AND THEN YOU HAVE MORE DETAILED
INFORMATION ENCAPSULATED IN YOUR
STANDARD OPERATING PROCEDURES.
THIS IS A VERY DETAILED WORKFLOW
OF EVERYTHING THAT'S GOING TO
HAPPEN ON EACH SAMPLE, EACH TYPE
OF PROCESS THAT YOU PERFORM.
WHEN YOU DO THIS, IT'S IMPORTANT
TO BE IN CONTROL OF YOUR
DOCUMENTS.
SO I'VE RECOMMENDED A DOCUMENT
CONTROL SYSTEM WHERE YOU CREATE
AN AUDIT OF EVERYTHING THAT'S
EVER HAPPENED WITH THE DOCUMENT
AND SHOWING THAT THE DOCUMENTS
ARE VETTED SO THEY'RE WELL
REASONED, THEY'RE UP TO DATE,
THEY'RE UNDERSTOOD, THEY'RE
VERSIONED AND YOU KEEP THE
VERSION, THE KEEP THE VERSION
HISTORY.
THEY'RE ACCURATE AND UP TO DATE.
THERE'S THIS THING CALLED SOP
DRIFT, SO YOU'RE USING YOUR SOP
BUT OVER TIME YOU START TO TWEAK
IT A LITTLE BIT HERE AND THERE
AND HERE AND THERE AND HERE AND
THERE.
EVEEVENTUALLY YOU REALIZE THE SP
IS NOT THE SAME AS WHAT YOU'RE
DOING SO YOU NEED TO GO BACK AND
RE-ADJUST IT AND REAPPROVE IT.
DISTRIBUTE TO AUTHORIZED
PERSONNEL AND APPROPRIATELY
RETAINED OR DISPOSED.
THIS IS ACTUALLY A QUICK NOTE ON
SAMPLE COLLECTION AND
PROCESSING.
THIS IS WHAT OUR STUDY STRUCTURE
FOR THE UM PREGNANCY BIOBANK
LOOKS LIKE, AT LEAST IN PART SM
HERE'S THE STUDY, THE COHORT OF
MOTHERS, PREGNANCY VISIT, SO
THERE'S ONE, TWO AND THREE.
THERE'S PRELABOR AND DELIVERY,
AND THEN LABOR AND DELIVERY.
IN THIS PARTICULAR CASE -- SO
THIS IS ALL MAPPED OUT AHEAD OF
TIME.
AND THEN WE HAVE IN THE -- I
CAN'T REALLY SEE IT HERE BECAUSE
OF THE -- ANYWAY, THESE ARE THE
KITS.
OBSTETRICS, TISSUE, VISIT NUMBER
THREE ONLY, THAT'S FOR THE BABY
KIT.
AND THEN THERE'S THE KIT ITEMS.
EACH OF THESE ITEMS HASTY OWN
BARCODE AND LABEL.
WE DON'T KEEP ANY PHI ON THE
BARCODES THEMSELVES.
OR SORRY ON THE LABELS
THEMSELVES, ONLY THE SAMPLE
BARCODE.
SO THIS WAY ALL OF OUR SAMPLES
ARE DE-IDENTIFIED.
AGAIN THESE ARE JUST SPECIFIC TO
THE UM PREGNANCY BIOBANK.
AND THERE'S A WHOLE HOST OF
OTHER TYPES OF KIT ITEMS THAT
CAN BE THROWN INTO THE KIT, EACH
WITH ITS OWN INDIVIDUAL LABEL.
SO THIS IS ANOTHER THING THAT I
HIGHLY RECOMMEND.
THIS IS A WORKFLOW MAP OF
EVERYTHING THAT HAPPENS IN THE
BIOREPOSITORY FROM THE
COLLECTION IN THE CLINIC TO HOW
PEOPLE ARE CLENGTING COLLECTINGE
SAMPLES, WHERE ARE THEY STORED
TEMPORARILY, WHERE ARE THEY
STORED LONG TERM.
SO THIS IS A CRITICAL COMPONENT
THAT WILL HELP YOU DEVELOP NOT
ONLY YOUR PROCESS ITSELF BUT
ALSO ALL OF THE ITEMS YOU NEED
TO SUPPORT YOUR PROCESS AND
WHO'S GOING TO DO IT.
AND I RECOMMEND HAVING SOMEBODY
WHO KNOWS HOW TO DO THIS.
THIS IS A BUSINESS SYSTEMS
ANALYST, FOR EXAMPLE.
YOU MAY ALSO WANT TO CONSIDER A
QUALITY MANAGEMENT PROGRAM FOR
YOUR BIOBANK, WHICH WILL SUPPORT
CONFIDENT STEWARDSHIP OF YOUR
BIOLOGICAL SPECIMENS, ALSO
PREVENTS MISTAKES, ALLOWS T YOUO
COLLECT ANNUALLY OR MORE
FREQUENTLY AS YOU WISH.
YOU ARE REDUCING WASTEFUL
ACTIVITIES.
ONE MAY SAY THAT QUALITY CONTROL
SYSTEM IS WASTEFUL IN AND OF
ITSELF.
I WOULD DISAGREE WITH THAT.
IT IS MORE WORK, IT REQUIRES
MORE RESOURCES, BUT THE BENEFITS
ARE OUTLINED HERE.
YOU ACTUALLY HAVE LOWER OVERALL
COSTS BECAUSE YOU'RE NOT DOING
WASTEFUL THINGS.
THEN YOU ALSO KEEP TRACK OF A
LIVING HISTORY.
SO THAT'S CRITICAL.
A COUPLE OF QMSs OUT THERE FOR
BIOBANKS THEMSELVES.
ONE IS CALLED -- ONE IS
ADMINISTERED BY THE COLLEGE OF
AMERICAN PATHOLOGISTS WHICH IS
THE BIOREPOSITORY ACCREDITATION
PROGRAM.
THE CENTRAL BIOREPOSITORY AT
MICHIGAN IS ACCREDITED BY THIS
BODY.
THERE IS ALSO AN ISOBIOBANK
STANDARD, WHICH IS
INTERNATIONAL.
SO I JUST WANT TO GIVE YOU A
LITTLE BIT OF A SCARE, SORRY, SO
THE MICHAEL J. FOX FOUNDATION
SUES CORIELL INSTITUTE OVER AN
ALLEGED FREEZER DOOR BLUNDER.
SO SOMEBODY FORGOT TO CLOSE A
FREEZER DOOR AND THEY LOST THE
SAMPLES.
SEUF HEARD THESE HORROR STORIES.
THIS IS JUST ONE.
SO TO PREVENT THAT, I JUST WANT
TO HIGHLIGHT, CHECKLISTS ARE
YOUR FRIEND.
EVEN IF YOU DON'T HAVE A QMS, A
FORMAL QMS, SOME END OF THE DAY
CHECKLISTS ARE PROBABLY A GOOD
IDEA.
THIS IS OURS, ONE OF OURS.
WE CHECK THE FREEZER DOOR IS
CLOSED, WE ALSO CHECK THAT THE
FACEPLATE IS REGISTERING A
TEMPERATURE AND MATCHES THAT OF
OUR SECONDARY TEMPERATURE PROBE
SYSTEM.
AND THEN WE ALSO DO A CHECK-IN
EVERY SINGLE DAY TO MAKE SURE
ALL SAMPLES ARE CHECKED IN.
YOU CAN SEE THAT PRO TIP AT THE
TOP.
DON'T THINK THAT YOU'RE GOING TO
DO IT TOMORROW.
DO IT TODAY.
BECAUSE YOU WILL LOSE TRACK OF
YOUR SAMPLES.
THEY SHOULD BE ACCESSIONED IN
THE ELECTRONIC SYSTEM AND PUT IN
THE FREEZER.
IF THEY CAN'T BE PUT PERFECTLY
AWAY, AT LEAST ACKNOWLEDGE THEIR
RECEIPT AND THEIR LOCATION IN A
BOX.
THEN WHILE YOU'RE MAKING OR
CREATING A BIOREPOSITORY, IT MAY
FEEL LIKE YOU'RE DRIVING A CAR
WHILE YOU'RE BUILDING IT AND YOU
ARE, AND THAT'S OKAY.
WITH THE GOOD INFRASTRUCTURE AND
THE GOOD FOUNDATION, YOU WILL BE
ABLE TO GET TO YOUR DESTINATION
SAFELY.
BUT IT DOES TAKE A TEAM, SO I
JUST WANTED TO HIGHLIGHT THE
CENTRAL BIOREPOSITORY TEAM WHO
ARE DOING ALL OF THIS WORK.
OUR HEALTH INFORMATION
TECHNOLOGY COLLEAGUES AT OUR
HITS DEPARTMENT.
OUR SPONSORS AT THE UMMS OFFICE
OF RESEARCH, AND OUR FACILITIES
GUYS WHO JUST MAKE SURE
EVERYTHING WORKS FOR US.
EXCELLENTLY.
OH, AND THEN I'VE PUT THESE
RESOURCES OUT THERE IF YOU WANT
TO TAKE A PICTURE, I DON'T KNOW
IF THE SLIDES WILL BE
DISTRIBUTED BUT IF THEY ARE,
THEN YOU'LL HAVE THEM.
THANK YOU.
>> THANK YOU, DR. BLANC.
OUR NEXT TALK IS ON DEVELOPMENT
AND EXPANSION OF THE WOMEN'S
HEALTH TISSUE REPOSITORY AND
INTERGENERATIONAL HEALTH
KNOWLEDGEBASE AT THE UNIVERSITY
OF IOWA BY DRS. DONNA AND MARK
SANTILLAN.
>> THANK YOU FOR ALLOWING US TO
TALK ABOUT OUR WORK AT THE
UNIVERSITY OF IOWA.
WE'RE GOING TO TALK ABOUT OUR
WOMEN'S HEALTH TISSUE
REPOSITORY.
OKAY.
SO I'M DONNA SANTILLAN, DIRECTOR
OF WOMEN'S HEALTH TISSUE
REPOSITORY AND THIS IS MARK, OUR
CLINICAL DIRECTOR, AND WE'RE
ALSO GOING TO BEING TALKING
ABOUT OUR WORK AROUND THE
KNOWLEDGE BASE.
I'M SURE I'M PREACHING TO THE
AUDIENCE HERE, I'M PREACHING TO
THE CHOIR.
WHEN WE STARTED OUR BIOBANK BACK
IN 2009 THERE HAD BEEN A REPORT
FROM THE NATIONAL ACADEMY OF
MEDICINE ABOUT HOW TO IMPROVE
WOMEN'S HEALTH RESEARCH AND WHAT
WAS NEEDED, AND THERE WERE
SEVERAL RECOMMENDATIONS THAT
WERE MADE IN THERE, INCLUDING
MAINTAINING AND INCREASING AN
EMPHASIS ON MOLECULAR ANIMAL
CELLULAR OBSERVATIONAL AND
CLINICAL STUDIES RESEARCH SO
BASICALLY ACROSS THE
TRANSLATIONAL SPECTRUM,
INCLUDING WOMEN IN RESEARCH THAT
HAVE HIGHEST RISK AND HIGHEST
DISEASE BURDENS, PROMOTING
WELLNESS AND QUALITY OF LIFE
RESEARCH, IN ADDITION TO
MORTALITY STUDIES.
STUDYING COMMON DETERMINANTS AND
RISK FACTORS UNDERLYING MULTIPLE
DISEASES, IMPROVING SEX
STRATIFIED ANALYSES,
IMPLEMENTING RESEARCH USING THE
STUDY FINDINGS AND IMPROVING THE
COMMUNICATION OF RESEARCH
FINDINGS.
SO WE FELT BY DEVELOPING A
BIOBANK AT THE UNIVERSITY THAT
WE WOULD BE HELPING TO ADDRESS
THESE AREAS.
SO BECAUSE YOU CAN'T REALLY
EXPERIMENT ON PREGNANT WOMEN, WE
THOUGHT THAT BIOBANKING WAS ONE
OF THE ANSWERS THAT WE WERE
GOING TO DO.
SO WE CREATED THE WOMEN'S HEALTH
TISSUE REPOSITORY.
THAT STARTED IN 2010 AND IT
ACTUALLY CONSISTS OF FOUR
DIFFERENT BIOBANKS, SO THAT
WE'RE GIVING PATIENTS CONSENT
FORMS THAT FIT THEIR NEED.
WE'RE NOT GIVING A PATIENT WHO
HAS -- WHO'S PREGNANT SOMETHING
THAT'S TALKING ABOUT HER CANCER
COLLECTION, AND IN OUR
INFERTILITY PATIENTS WE'RE A
LITTLE BIT MORE SENSITIVE ABOUT
THE LANGUAGE ON PREGNANCY AND
THEIR CHILDREN AND HOW WE WORD
THINGS.
SO WE HAVE FOUR DIFFERENT
CONSENTS, THE PERINATAL FAMILY
TISSUE BANK, REBRAND OF OUR
PREVIOUS BANK SO THIS NOW
INCLUDES MALE PARTNERS AND IT
ALSO INCLUDES -- IT'S JUST TO BE
MORE GENDER INCLUSIVE IN OUR
LANGUAGE AS WELL.
FOR THIS WE'RE CONSENTING FOR
THE LONGITUDE OF THE PREGNANCY,
THE PREGNANT PATIENT IS GIVING
US CONSENT GOING FORWARD AND
BACKWARD FOR THEIR MEDICAL
RECORD AND WE'RE ALSO RECEIVING
CONSENT FOR THE CHILD TO LOOK AT
THEIR MEDICAL RECORD UNTIL THEY
TURN 18.
THE REPRODUCTIVE ENDOCRINOLOGY
AND FERTILITY TISSUE AND DATA
BANK IS FOR PATIENTS BEING SEEN
IN REI, LARGELY OUR INFERTILITY
PATIENTS.
A WELL WOMAN BANK MOSTLY HAS
UROGYNECOLOGY PATIENTS IN IT
RIGHT NOW, THEN OUR GYN ONG
BANK, THESE ARE THE NUMBER OF
PARTICIPANTS WE HAVE IN EACH
BANK.
YOU'LL SEE AS WE TALK ABOUT
TODAY, THE PREGNANCY BANK HAS
OVER 13,000 PARTICIPANTS.
SO WE ARE ONLY CONSENTING AT THE
UNIVERSITY OF IOWA FOR PATIENTS
TO PARTICIPATE, WE'VE
OCCASIONALLY HAD SOME GRANTS
THAT HAVE ALLOWED US TO CONSENT
OUTSIDE BUT IT'S LARGELY
INTERNAL CONSENTING.
PART OF THAT IS BECAUSE OUR
WHOLE HOSPITAL SYSTEM IS ON EPIC
SO INPATIENT, OUTPATIENT, ALL OF
THE CLINICS, EVERYTHING IS EPIC
AND FOR THE CHILDREN TOO, SO IT
MAKES IT MUCH EASIER TO GET THE
LONGITUDAL DATA.
WE TRIED TO MAKE THIS AS SIMPLE
AS POSSIBLE SO WE COLLECT AN
EXTRA TUBE ALONGSIDE CLINICALLY
INDICATED SAMPLES THAT SAVED US
A BIT OF MONEY BECAUSE WE DIDN'T
HAVE TO PAY PHLEBOTOMY TO DRAW
OUR SAMPLES, AS LONG AS THEY
WERE DREWING A T DRAWING A TEU D
COLLECT OURS.
WE ARE COLLECTING AN EXTRA TUBE
OF BLOOD FOR RESEARCH, IT'S
ALWAYS THE SAME TUBE.
WE CODE ALL OF OUR SAMPLES TO
PROTECT PATIENT PRIVACY.
SO THERE'S A PARTICIPANT I.D.
THAT IS UNIQUE TO THE FAMILY, SO
WE CAN TELL WITH THOSE TOGETHER
WHO BOTH OF THE PARENTS ARE BUT
ALSO IF YOU ARE ENROLLED IN
MULTIPLE BIOBANK, SO IF YOU'RE
AN INFERTILITY PATIENT AND YOU
BECOME PREGNANT AND LATER ON
YOU'RE GETTING ANNUAL CARE OR
YOU WOULD DEVELOP CANCER, YOU
WOULD ALWAYS HAVE THE SAME
PARTICIPANT I.D. AND WE CAN TELL
HOW THOSE SAMPLES GO TOGETHER
AND THERE'S A EU MEEK CODE
SHOWING WHICH BANK THOSE SAMPLES
PLOBELONG TO.
AFTER WE HAVE APPROVALS,
RESEARCHERS CAN OBTAIN SAMPLES
AND THEIR NEEDED CODED CLINICAL
DATA.
SO WE PROVIDE ALL OF THE
CLINICAL DATA TO THEM AND THEY
DON'T -- WE HAVE IRB APPROVAL AS
A TISSUE BANK, SO IF THEY JUST
USE CODED INFORMATION, THEY
DON'T NEED THEIR OWN IRB
APPROVAL, THEY CAN GET A HUMAN
SUBJECTS RESEARCH DETERMINATION,
WHICH IS MUCH QUICKER THAT
ALLOWS THEM US TO GIVE THEM THE
SAMPLES AND DATA.
THIS HAS BEEN BENEFICIAL FOR
OTHER STUDIES THAT NEED PATIENTS
POSTPARTUM OR STUDIES THAT DON'T
NEED SAMPLES AS ALL, SURVEYS OR
THINGS LIKE THAT, OR JUST
DIFFERENT OPPORTUNITIES THAT
DON'T REALLY LINE UP WITH THE
SAMPLES THAT THEY HAVE ALREADY
LISTED PATIENTS WHO ARE
INTERESTED IN PARTICIPATING AND
WHO WE KNOW SOME INFORMATION
ABOUT SO THEY CAN CONTACT.
WE HAVE A UNIVERSITY LIMB SYSTEM
PROVIDED BY THE UNIVERSITY,
UIBIOSHARE.
WE ARE ONE OF THE EXECUTIVE
MEMBERS OF THAT TEAM SO ALL OF
THE LARGE BIOBANKS ON CAMPUS
STORE OUR INFORMATION IN HERE.
THEY GOT TOGETHER WHEN THE
SYSTEM WAS IMPLEMENTED AND
DECIDED HOW WE WERE GOING TO
LABEL SAMPLES, HOW WE WERE GOING
TO STORE INFORMATION, SO
EVERYTHING IS DONE THE SAME.
OUR GROUP DOESN'T SAY
MALE/FEMALE AND ANOTHER GROUP
SAYS GIRL/BOY OR 1s AND
ZEROs.
IT'S ALL THE SAME SO IT MAKES IT
EASIER TO FIND SAMPLES ON CAMPUS
AND WE HAVE COMMON DATA FORMS
THAT WE ENTER INTO.
THE UI BIOSHARE SYSTEM LET'S US
PUT IN INFORMATION ABOUT THE
PARTICIPANT, IT'S LINKED TO
THEIR SAMPLES AND CONSENT
INFORMATION.
WE ALSO DO COLLABORATE WITH OUR
TISSUE PROCUREMENT CENTER.
THAT'S MOSTLY FOR OUR
GYNECOLOGIC BANKING OR FAMILIAR
SELLS THAT ARE GOING TO SPES MIN
CONTROL OR TO PATHOLOGY.
AND THEN WE PROCESS OUR SAMPLES
USING STANDARD OPERATING
PROTOCOLS.
THEY'RE STORED IN TEMP TRACKED
FREEZERS AND MONITORED AND WE
HAVE 24/7 MONITORING.
OUR INCLUSION CRITERIA RIGHT
NOW, YOU HAVE TO BE ENGLISH
SPEAKING BECAUSE THAT'S WHAT OUR
CONSENTERS SPEAK.
WE'RE WORKING ON GETTING THAT IN
DIFFERENT LANGUAGES.
YOU HAVE TO BE OVER 18.
14 IN THE -- WE HAVE A CONSENT
DOCUMENT FOR THAT.
NON-PRISONERS, BECAUSE IT TAKES
TIME IF WE HAVE TO GO THROUGH
THE PRISONER REVIEW BOARD.
WE GET INFORMED CONSENT FROM ALL
OF OUR PATIENTS, AND IT SAYS
THAT THEIR SAMPLES COULD BE USED
FOR THINGS THAT WE MAY NOT EVEN
KNOW AND NOT FOR THE FUTURE.
WE'RE GOING TO COLLABORATE,
WE'RE GOING TO SHARE THEIR
SAMPLES.
SO IT'S A PRETTY BROAD CONSENT
FOR WHAT WE'RE GOING TO USE IT
FOR.
AND EXCLUSION, THEY'RE NOT HIV
OR HEPATITIS C POSITIVE.
AND THAT'S REALLY JUST FOR THE
SAFETY OF THE PEOPLE PROCESSING
THE SAMPLES.
OUR SAMPLE COLLECTIONS ARE
COINCIDENT WITH CLINICAL SAMPLE
COLLECTIONS.
OFTEN THEY EVEN FORGET THEY'RE
ENROLLED.
WE'RE JUST AN EXTRA TUBE THAT
THEY THROW ON, IT'S THEIR CORD
BLOOD AND PLACENTA THAT'S
NORMALLY DISCARDED BUT IF
PATIENTS ARE TIRED AND THEY JUST
ARE LIKE I DON'T WANT TO DO AN
EXTRA TUBE OF BLOOD TODAY,
THAT'S FINE, THEY STILL REMAIN
IN THE STUDY, OR IF PATIENTS
WANT TO TAKE HOME THEIR PLACENTA
AND DON'T WANT TO DONATE IT OR
THEY WANT TO LET US HAVE A PIECE
AND THEN THEY WANT IT BACK,
THAT'S ALSO FINE.
AT THE UNIVERSITY PLACENTAS ARE
EXCLUDED FROM THE REQUIREMENT TO
GO TO PATHOLOGY SO THAT MAKES IT
A BIT EASIER FOR US BUT IF THEY
DO NEED TO GO, WE HAVE AN
AGREEMENT WITH PATHOLOGY THAT WE
WILL TAKE PLA 16 TAS THERE FRESH
AND THEY WILL LOOK AT THEM RIGHT
AWAY.
SO THIS IS JUST DURING DAY TIME
HOURS FOR PEOPLE IN THE BANK AND
FOR PEOPLE WHOSE SAM PES HAVE TO
GO TO PATH.
SO IT'S VERY FEW SAMPLES A MONTH
THAT THIS HAPPENS AND THIS WORKS
OUT JUST FINE FOR US.
ALL TUMORS GO TO PATHOLOGY AND
THE TISSUE PROCUREMENT CORE
RETRIEVES THEM FROM GROSS
PATHOLOGY FOR THE GYN ONC BANK
AND THEN WE GET THEM AFTER THAT.
SO THE SAM P SAMPLES THAT WE CO,
MATERNAL, PATERNAL BLOOD, WE
TAKE THAT, WE PROCESS IT INTO
PLASMA AND ALSO STORE THE --, WE
COLLECT M MATERNAL URINE IN EACH
TRIMESTER.
CORD BLOOD, AND THEN PLAT 16 TA
WHICH WE STORE BY LAYERS AND WE
ALSO STORE CORE THICKNESSES AND
WE STORE THAT IN LIQUID NITROGEN
AND TUBES.
WE ALSO COLLECT SEMINAL FLUID,
FOLLICULAR FLUID, WE GET THE
TUMOR IN THE NORMAL ADJACENT
TISSUE.
THERE ARE SURVEYS WE ASK
PATIENTS TO FILL OUT AND THEN WE
GET THE CLINICAL DATA AS WELL.
WE DID PUBLISH THIS IN 2014.
SO FOR THE SAMPLE PROCESSING I
MENTIONED WE COLLECT PERIPHERAL
BLOOD AND ACROSS ALL OF THE
BANKS WE COLLECT THE BLOOD IN
THE SAME TUBE SO IF WE ARE
LOOKING AT PRE OR POST PREGNANCY
SAMPLE FROM A DIFFERENT BANK, IT
WAS COLLECTED IN THE SAME TUBE
AND PROCESSED THE SAME WAY.
WE USE THE ACDA TUBE WHICH IS A
CITRATED TUBE, NOT AS COMMON FOR
PEOPLE BUT WE CHOSE THAT BECAUSE
IT STORES THE EX-SOMES WELL, WE
CAN GET THE PLASMA, THE -- CODE
OUT OF THE SAME TUBE.
WE WORKED WITH BD WHEN WE MADE
THAT SAMPLE CHOICE.
WE WERE GS GOING EDTA FOR
MOLECULAR STUDIES LATER ON.
WE KEEP THE PLAT MA -- WE MAKE
ALIQUOTS RIGHT AWAY.
IN OUR BIOSHARE SYSTEM, WE CAN
TELL EVERYTHING HAS A BARCODE
AND EACH ALIQUOT HAS A BARCODE
AND WE KNOW WHAT PARENTAL
SAMPLE, WHAT ORIGINAL SAMPLE IT
CAME FROM, WHO PROCESSED IT,
WHEN IT WAS COLLECTED, WHEN IT
WAS PROCESSED, WHO STORED IT,
ALL OF THE DETAILS ABOUT IT, AND
IF IT WAS BLOODY OR SOMETHING
LIKE THAT, WE MAKE NOTES ABOUT
IT THERE.
ALL OF THE SAMPLES ARE STORED AT
MINUS 80 IN TUBES WITH O-RINGS,
AND WE STORE THE CELLS PROVIDED
IN LIQUID NIGHT GIN.
NITROGEN.
THE URINE IS EXTRA FROM CLINICAL
SAMPLES, WE'RE ALSO ALLOWED TO
ASK FOR EXTRA IF THEY DON'T GET
ONE IN A TRIMESTER, WE ALIQUOT
THAT AS WELL AND STORE IT AT
MINUS 80.
FOLLICULAR FLUID NORMALLY
DISCARDED -- AND THE PELLETS AND
WE STORE THOSE.
UMBILICAL CORD BLOOD, WE PROCESS
THAT, THAT'S COLLECTED IN THE
CORD BLOOK COLLECTION BAG.
IN THE PLACENTA, SOMETHING
THAT'S NORMALLY DISCARDED, WE
STORE BY LAYERS.
IN THE TUMOR, THE CLINICAL
SAMPLES ARE TAKEN FIRST AND THEN
WE STORE THAT IN LIQUID
NITROGEN.
AS I MENTIONED WE ALSO GET
SURVEYS FROM PARTICIPANTS.
WE ALSO HAVE A REALLY HIGH
PARTICIPANT SURVEY RETURN RATE.
IT'S WELL OVER 80% IN THE FIRST
TRIMESTER AND IF THEY RETURN
THEM IN THE FIRST, THEN IT'S
OVER 90 FOR THE SECOND AND THIRD
TRIMESTER.
WE ASK THEM ABOUT THEIR
EDUCATION, MARITAL STA TURKS
INCOME, SMOKING AND VAPING.
THAT IS TO GET MORE TEE TAILS
THAN WHAT IS CURRENTLY COLLECTED
CLINICALLY.
WE HAVE SOME COVID QUESTIONS
ABOUT EFFECTS TO THEIR
PREGNANCY.
WE'RE ALSO ASKING ABOUT
ENVIRONMENTAL EXPOSURE, AND
THEIR DRINKING WATER SOURCE.
THAT THEY'RE USING AT HOME.
THEN IN THE WELL WOMAN BANK, WE
HAVE QUALITY OF LIFE SURVEYS,
MOSTLY ABOUT OVERACTIVE BLADDER
SYMPTOMS.
WE DO SHARE OUR SAMPLES.
THEY'RE NOT JUST USED AT THE
UNIVERSITY OF IOWA.
WE HAVE TEEFERL TRANSFER
AGREEMENTS WITH DATA USE
AGREEMENTS.
YOU HAVE TO AGREE TO BE THE END
USER AND THAT YOU WON'T BE
PASSING ON THE SAMPLES.
WE WORK WITH OUR UI DIVISION OF
SPONSORED PROGRAMS AND THEY KNOW
OUR SYSTEM NOW SO IT DOESN'T
USUALLY TAKE THAT LONG.
WE DO HAVE TO GO THROUGH DATA
GOVERNANCE APPROVAL IF WE'RE
SENDING OUT CLINICAL DATA
BECAUSE ANYTHING GENERATED IN
OUR MEDICAL RECORD NEEDS THAT
APPROVAL.
THEN OUR COLLABORATORS RECEIVE
CODED SAMPLES WITH THE
CORRESPONDING CODED CLINICAL
INFORMATION.
SO WE HAVE FOUND THAT OUR BANKS
REALLY ARE FULFILLING NEEDS IN
WOMEN'S HEALTH RESEARCH SO JUST
LOOKING AT THE PERINATAL FAMILY
TISSUE BANK, OUR PREGNANCY BANK
AS AN EXAMPLE, THERE'S ALMOST
7500 MATERNAL CHILD PAIRS.
WE CONSENT ON AVERAGE ABOUT 70
PEOPLE A MONTH TO THIS AND ABOUT
87% OF THE PEOPLE WE APPROACH
CONSENT.
WE HAVE MULTIPLE CLINICS THAT WE
HAVE TO COVER SO WE TRY TO GET
TO EVERY PATIENT AS SOON AS
POSSIBLE.
WE HAVE A CONFIRMATION TO
PREGNANCY APPOINTMENT THAT
OCCURS BETWEEN 6 TO 10 WEEKS
THAT WE TRY TO APPROACH AT OR
ELSE WE GO TO THEIR NEW OB
VISIT.
WE HAVE OVER 120,000 ALIQUOTS.
THESE SAMPLES HAVE BEEN USED IN
STUDYS THAT RANGE FROM
PREECLAMPSIA TO SUICIDE IDEATION
TO ENVIRONMENTAL STUDIES, GROUP
B STREP, SMN, NEURODEVELOPMENTAL
DISORDERS, AS PRIN.
REALLY A WIDE RANGE OF STUDIES.
OVER 150 PROJECTS PROJECTS.
BUT HAVING SAMPLES IS ONLY ONE
HALF OF WHAT YOU NEED.
YOU REALLY NEED DEEP CLINICAL
DATA ABOUT THESE SAMPLES AND SO
WE WORK TO DEVELOP THE
INTERGENERATIONAL HEALTH
KNOWLEDGE BASE, THAT MARK WILL
TALK ABOUT.
>> HI.
AGAIN, THANK YOU FOR THE
ORGANIZERS FOR INVITING US TO
TALK ABOUT SOME OF THESE
RESOURCES WE HAVE AT THE
UNIVERSITY OF IOWA.
SO BIOSAMPLES WITHOUT KIND OF
HIGH RESOLUTION CLINICAL DATA IS
NOT AS HELPFUL AND SO ONE OF THE
THINGS THAT SOMEONE BROUGHT UP
EARLIER IS THIS IDEA OF A
SINGULAR ID THAT LINKS MOM AND
BABY DATA AND I THINK THAT'S
PART OF THE POWER OF THIS
INTERGENERATIONAL HEALTH
KNOWLEDGE DATABASE.
SO THE IHK IS AN INTEGRATED
INFORMATION DATA MART THAT TAKES
EVERYTHING IN OUR EH R AND PUTS
IT INTO A SINGULAR -- WHAT WE
CALL OBDR, TO A COMMON SEMANTIC
LAYER USING VERY STANDARDIZED
VOCABULARIES LIKE ICD10 CODES,
LOINC CODES, TO GIVE YOU AN IDEA
OF WHAT THIS WHOLE ARCHITECTURE
LOOKS LIKE.
IF YOU LOOK AT THE LEFT MOST SET
OF COLUMNS, THESE ARE YOUR
EXTERNAL DATA SOURCES, WHETHER
IT'S EMIK EPIC OR EHR OR EXTERL
EHRS, REDCAP, BIOSAMPLES, WHAT
HAVE YOU, THAT GETS FED INTO OUR
SYSTEM AND ALL OF THAT DATA GOES
INTO WITHIN THE HEALTHCARE
ENTITY, SO IT'S ALL I
HIPAA-COMPLIANT THAT GOES INTO A
COMMON SEMANTIC LAYER INTO THESE
INTEGRATED STRUCTURES, WHETHER
IT'S PATIENT DEMOGRAPHIC
INTEGRATED DATA, SCRIPTS, LABS,
PRETTY MUCH ANYTHING YOU THINK
YOU WOULD NEED OUT OF YOUR EHR.
AS WE ARE CURRENTLY APPLYING FOR
FUNDING TO GET THAT OUT OF THOSE
SEMANTIC LAYERS TO PUT INTO SOME
OF OUR NETWORKS, LIKE OMOP AND
FIRE, SO YOU HAVE THESE
INTEGRATED DATA STRUCTURES THAT
ARE -- THAT FORM THESE
TRANSFORMATIVE DATASETS.
THE IHK IS THE FIRST OF THOSE AT
THE UNIVERSITY OF IOWA, BUT WHEN
YOU'VE GOT A GOOD IDEA, THEY
TEND TO METASTASIZE, SO THERE
ARE OTHER INTEGRATIVE
TRANSFORMATIVE DATASETS THAT ARE
HAPPENING AT THE UNIVERSITY OF
IOWA, WHETHER IT'S PSYCHIATRY,
NEUROSCIENCE OR WHAT YOU HAVE.
THOSE DATASETS ARE KIND OF
LEGISLATED OVER BY DOMAIN
EXPERTS THAT FEED INTO THE BMI,
WHICH IS THE BIOINFORMATICS
THEME AT OUR ICTS.
SO DONNA AND I FOR OB-GYN ARE
THE DOMAIN EXPERTS TO HELP FORM
THOSE DATASETS AND BETA TEST A
LOT OF THOSE VERY SPECIFIC
VARIABLES TO MAKE SURE THAT IF
YOU'RE GETTING APGARS AT FIVE
MINUTES, THAT IT'S TRULY THE
APGAR AT FIVE MINUTES.
THERE IS A CLEAR GOVERNANCE
REVIEW PROCESS, AND THEN THIS IS
AVAILABLE TO RESEARCHERS NOT
ONLY INTERNALLY BUT EXTERNALLY
AND ONE OF THE POWERS THAT WE
HAVE EMPLOYED AT THE UNIVERSITY
OF IOWA IS THAT A LOT OF THIS
DATA SITS IN A PROTECTED DATA
ENCLAVE, SO RESEARCHERS CAN USE
HIGH PERFORMANCE DATA COMPUTING
TOOLS TO GET INTO THIS DATA
ENCLAVE IN A VERY HIPAA
COMPLIANT WAY IN ORDER TO DO
SOME HIGH -- TO DO A LOT OF
ANALYSES, FOR EXAMPLE, WE'VE
DONE A.I. USING A LOT OF OUR EHR
DATA.
THERE ARE ABOUT 77,000 EPISODES
IN OUR IHK.
ALL THE INBORN CHILDREN, THERE'S
ABOUT 10,000 BABIES, ALL
CHILDREN TRANSFERRED UP TO 30
DAYS OF LIFE, WE'VE GOT 44,000
BABIES.
THIS IS UP DATED WEEKLY, AND WE
AS USERS ARE TRAINED DATA
LIAISONS AND ACCESS THE HONEST
BROKERS FOR PEOPLE THAT WANT TO
DUSE THAT.
WE HAVE AN IRB-APPROVED FILTER.
DONNA AND I DO NOT KNOW HOW TO
USE SEQUEL DATABASE, WE ARE NOT
PROGRAMMERS BUT TO GET ALL OF
THIS DATA, WE HAVE WORKED WITH
OUR BMI GROUP TO DO SOMETHING
LIKE THIS, WHERE WE COULD
LITERALLY JUST PUT IN THE ICD10
CODE FOR ANYTHING AND
WITHIN SECONDS, I CAN GET
EVERYONE WHO HAS PREECLAMPSIA OR
WHATEVER ICD10 CODE I COME UP
WITH.
THESE VARIABLES ARE VERY
DYNAMIC.
WE STARTED OFF WITH EVERYTHING,
AND THEN PEOPLE WANT NEW THINGS
THAT WE HAVEN'T FOUND LIKE THE
HQ9 NOW THAT'S IN OUR DATA MART,
SO WITH EVERY NEW STUDY, WE'RE
ABLE TO CHANGE THE DATA MART.
IF YOU'RE INTERESTED IN GETTING
DATA, THERE'S DONNA'S EMAIL
ADDRESS BUT WE HAVE A LOT OF
ONLINE POSSIBILITIES IN ORDER TO
CONTACT US WITH REGARD TO
GETTING SAMPLES AND/OR DATA.
THANK YOU.
>> OUR NEXT TALK IS OUR LAST
TALK FOR THIS SESSION, IT'S ON
HUGEAMP ON PREGNANCY TRAITS BY
DRS. NOEL BURTT AND JASON
FLANNICK FROM THE BROAD
INSTITUTE.
>> GOOD MORNING.
WE'RE EXCITED TO BE HERE AS
HUMAN GENETICISTS WHO
PREDOMINANTLY STUDY -- REALLY AN
EDUCATIONAL TOUR FOR US, I
ACTUALLY HAVE ALREADY LEARNED
STUFF THIS MORNING AND I'M
REALLY EXCITED FOR TODAY'S
CONVERSATION LATER ON.
WE'RE GOING TO START TALKING TO
YOU ABOUT IS AN EARLY STAGE
KNOWLEDGE PORTAL FOR GENETICS
AND GENOMICS OF PREGNANCY
TRAITS.
FIRST WANT TO SET THE STAGE A
LITTLE BIT WITH WHY WE DO THIS.
WE BUILD KNOWLEDGE RESOURCES FOR
COMMON DISEASE.
WE WANT TO MAKE SURE THAT FOLKS
WHO ARE NOT EXPERTS IN THAT
DOMAIN CAN HAVE ACCESS TO THOSE
RESULTS AND DATA IN A WAY THAT
IS USEFUL TO THEM.
WHY DOES THAT MATTER?
WELL, HUMAN GENETICS HAS HAD
QUITE AN INCREDIBLE SORT OF
GOLDEN AGE IN THE PAST 10 YEARS.
IF YOU LOOK AT EACH ONE OF THESE
SPOTS IT'S A GENOME WIDE
SIGNIFICANT LOCUS FOR COMMON
DISEASE.
IF YOU STUDY THESE IT WOULD TAKE
A LIFETIME.
SO PRETTY COMPLICATED FOR THE
AVERAGE INVESTIGATOR OR SOMEONE
IN AN INDUSTRY SETTING TO SAY
WHICH GENE SHOULD I STUDY AS
WAY.
MOREOVER, THESE ARE REGIONS OF
THE GENOME THAT MAY CONTAIN
MULTIPLE GENES FOR A PARTICULAR
DISEASE.
SO WADING THROUGH THESE, YOU'D
TAKE A LIFETIME.
SO WE ATTEMPT TO TRY TO MAKE A
RESOURCE THAT ALLOWS YOU TO MAKE
THOSE RESOURCE, EVEN IF YOU WERE
AN EXPERT AS A HUMAN GENETICIST
AND WANT TO PICK A LIST OF
TARGET GENES TO STUDY FOR YOUR
FAVORITE DISEASE OR WANT TO
WEIGH EVIDENCE FOR WHAT YOUR
FAVORITE GENE'S ROLE IS IN HUMAN
DISEASE YOU'D HAVE TO GO TO PUT
IN PEL DATABASES DOWNLOAD ALL
THE DAY TA RUN A META-ANALYSIS
YOURSELF, DO SOME LITERATURE
SEARCHES, UNDERSTAND MODEL
SYSTEM DATABASE, WHAT THAT TBEEN
IS INVOLVED IN, PULL ALL THIS
INFORMATION TOGETHER AND YOU'RE
PRETTY TIRED AT THE END.
SO OUR GOAL IS TO MAKE THIS
EASIER FOR YOU.
WE STARTED WITH THIS MANY YEARS
AGO IN THE TYPE 2 DIABETES
GENETICS WORLD.
WE WERE LU KE ENOUGH TO BE THE
DATA COORDINATING CENTER FOR THE
COMMUNITY.
WE WORKED WITH EXPERTS IN
GENETICS AND DIABETES AS A TRAIT
AND RELATED TRAITS AS WELL TO
TRY AND MAKE A RESOURCE TO MAKE
THESE RESULTS ACCESSIBLE TO
FOLKS WHO ACTUALLY CAN MAKE
DECISIONS ABOUT PREDICTION,
PREVENTION AND TREATMENT FROM
THE JE GENETIC STUDIES.
THIS IS THE KNOWLEDGE PORTAL FOR
TYPE 2 DIABETES.
THE ANIMATION IS GOING A LITTLE
SLOW.
THIS LED TO THIS PUBLICATION BUT
THIS HAS EXPANDED OVER THE PAST
COUPLE YEARS TO THE COMMON
METABOLIC DISEASE KNOWLEDGE
PORTAL.
THE HALLMARK OF THIS IS IT IS A
PUBLIC PRIVATE PARTNERSHIP BUT
WHAT'S REALLY CRITICAL IS WE'RE
WORKING VERY CLOSELY WITH PEOPLE
WHO ARE ACTUALLY STUDYING THE
DISEASES AND TRAITS THEMSELVES.
SO TO DO THAT, WE'VE ALSO
EXPANDED THIS RESOURCE TO
CARDIOVASCULAR DISEASE AND
CEREBROVASCULAR DISEASE.
AND OTHER TRAITS, SLEEP
DISORDERS, TYPE 1 DIABETES.
THE SIGNATURE HERE IS THAT THE
IDEA WE'RE WORKING DIRECTLY WITH
VECT TORE
INVESTIGATORS.
THE DISEASE, THE TRAITS, THE WAY
THAT THEY'RE PREPARED OR STUDIED
ARE VERY SPECIFIC TO THAT
CONSORTIUM AND THAT COMMUNITY.
SO OUR GOAL TO SCALE THIS IS TO
COLLABORATE DIRECTLY WITH
DISEASE COMMUNITIES TO
UNDERSTAND THEIR DATA, THE
METHODS, ANALYSES, AND ACTUAL
SPECIFIC SCIENTIFIC QUESTIONS
AND THE GAPS THEY'RE TRYING TO
ADDRESS WITHIN THEIR FIELD.
WE DO THIS BY ONBOARDING
PRECOMPUTED RESULTS OR
GENERATING SUMMARY
REPRESENTATIONS OF RAW DATA, AND
THEN CODING THOSE INTO A
SOFTWARE PLATFORM THROUGH
ANALYTICAL METHODS AND PROTOCOLS
AND PIPELINES AND CREATE VERY
SIMPLE VISUALIZATIONS THAT YOU
YOURSELF CAN USE EVEN IF YOU'RE
NOT AN EXPERT IN THAT FIELD.
WE MAKE SURE THAT WE DO THIS
THROUGH INTUITIVE AND HOPEFULLY
USER-FRIENDLY OPEN ACCESS
PORTAL.
SO WE'RE GOING TO TALK A LITTLE
BIT THAT BUT WHAT WE'VE RECENTLY
EXPANDED TO IS THE ASSOCIATION
TO FUNCTION KNOWLEDGE PORTAL,
FOR TRANSLATING GWAS LOCI FOR
COMMON DISEASE.
WHAT THIS DID FOR US IS IT
CREATED A PLATFORM FOR US TO DO
THIS WITH OTHER DISEASE
COMMUNITIES AND WE DON'T HAVE AS
MUCH EXPERTISE IN.
SO WE'VE BEEN VERY LUCKY TO
EXPAND THAT SO THAT THIS EFFORT
IS A LOT EASIER AND SO IN A
WORLD WHERE YOU USED TO HAVE TO
JUST DO ALL THOSE STEPS I
MENTIONED EARLIER, THE RESOURCE
MAKES IT SO YOU DON'T HAVE TO DO
ALL THOSE RESOURCES AND CAN YOU
FIND THE TOP GENES FOR YOUR
FAVORITE TRAIT OR THE ROLE YOUR
GENE HAS IN PARTICULAR DISEASE
VERY EASILY THROUGH THESE
VISUALIZATIONS.
SO WHAT ARE THE FUNDAMENTAL
DATASETS AND PIECES OF THOSE
PLATFORM?
FIRST IT'S GENETIC ASSOCIATIONS
WHICH I MENTIONED EARLIER.
WE GET THESE THROUGH SEVERAL
RESOURCE.
S.
WE WORK DIRECTLY WITH
INVESTIGATORS STUDYING THESE
DISEASES AND TRAITS WHO
UNDERSTAND THEM, HAVE THE DATA
AND HAVE THE UNDERSTANDING OF
HOW TO TRANSMIT THE DATA TO US
AND PROCESS IT.
WE ALSO WORK WITH DISEASE
AGNOSTIC RESOURCES LIKE THE GWAS
CATALOG AND GTEX AND N CODE
WHICH I'LL TALK A LITTLE ABOUT
IN A MINUTE.
SO FOR GENETIC ASSOCIATIONS OUR
FOCUS HAS BEEN REALLY TO FOCUS
ON THESE COMMUNITIES BUT WHAT
THIS HAS LED TO IS A THOUSAND
PHENOTYPES WITH 4,000
COLLABORATORS.
I'M A LITTLE AHEAD OF MY OWN
ANIMATION NOW.
THE OTHER LAYER FROM
FOUNDATIONAL DATA ARE FUNCTIONAL
GENOMIC ANNOTATIONS.
THIS TELLS YOU ABOUT THE
REGULATORY -- SO MANY OF THESE
ASSOCIATIONS ARE IN NON-CODING
REGION OF OUR GENOME SO YOU NEED
TO KNOW WHAT GENE IT'S ACTIVE IN
OR WHAT PATHWAY THAT IS, SO
THESE FUNCTIONAL GENOMIC
ANNOTATIONS HELP WITH THAT.
SO THIS IS A RESOURCE WE'VE
CREATED WITH UCSD AS WAREHOUSE
FOR THESE DATASETS WHERE THEY
HOUSE ABOUT 8,000 ANNOTATIONS
FOR SPECIFIC TISSUES RELATED TO
COMMON METABOLIC DISEASE AND YOU
CAN SEE THOSE LISTED HERE.
FINALLY TO PULL THIS ALL
TOGETHER, WE ENCODE BETION
PRACTICES IN OUR FIELD BY
WORKING WITH OUR FELLOW
GENETICISTS AND
BIOINFORMATICIANS TO ENCODE
METHODS TO HELP US GENERATE
HYPOTHESES ABOUT THE MOLECULAR
AND CELLULAR FUNCTION USING THE
GENETIC AND FOUNDATIONAL
FUNCTIONAL GENOMIC ANNOTATIONS.
IF YOU PULL THIS ALL TOGETHER,
IT'S A VERY FLEXIBLE PLATFORM
THAT HAS MANY COMPONENTS AND HAS
BEEN AROUND FOR ABOUT 10 YEARS
AND WE'VE BEEN ABLE TO ADAPT TO
DIFFERENT COMMUNITIES.
BUT ALSO EACH COMMUNITY WE
WORKED WITH HAS HAD DIFFERENT
CHALLENGES, WHETHER IT'S IMAGING
DATA OR DIFFERENT TYPES OF OMICS
DATA AND OUR GOAL HOPEFULLY
BEING HERE TODAY IS TO LEARN
SOME OF THE CHALLENGES IN YOUR
FIELD.
BUT LET'S TALK A LITTLE ABOUT
WHAT WE'VE DONE SO FAR.
MATERNAL HEALTH, I BRIEF IT'S BS
LACKING.
YOULAGGING.
BEST REPOSITORY FOR GWAS
STATISTICS IN THE WORLD,
ALZHEIMER'S, IBD, LOOK AT THE
NUMBER OF SAMPLES THAT HAVE BEEN
STUDIED AND THE NUMBER OF
DATASETS AS COMPARED TO MAJOR
TRAITS IN REPRODUCTIVE HEALTH.
PREECLAMPSIA, GDM.
IT'S INCREDIBLE.
EVEN THOUGH 50% OF THE
POPULATION ARE THESE PEOPLE YOU
CAN STUDY, IT'S PRETTY CRAZY.
BUT WHY IS THIS THE CASE?
IT'S STILL THE SAME HEALTHCARE
BURDEN.
IT'S ACTUALLY A PROBLEM OF TWO
WHEN YOU HAVE A MOTHER AND CHILD
BEING AFFECTED BY THIS.
I ACTUALLY DIDN'T APPRECIATE
THAT UNTIL I CAME TO TALK TO YOU
TODAY, IT'S QUITE REMARK ABLG.
BUT IT'S LIMITED IN SCALE AND
SCOPE.
I WOULD SAY EVEN THOUGH IT IS A
SET OF HAIRT TABL TRAITS, THIS
HAS NOT BEEN STUDIED TO MA THE
EXTENT OF MANY OF THE OTHER
DISEASES I TOLD BUT EARLIER.
GDM AND DIABETES HAVE A
RELATIONSHIP AND MANY WOMEN THAT
HAVE GDM AT BIRTH GO ON TO
DEVELOP DIABETES LATER ON IN
LIFE SO THERE'S SUCH A
CONNECTION HERE.
IF YOU LOOK AT THE LAST COUPLE
YEARS ACTUALLY IN OUR FIELD,
GENOMICSGENETICS HAS STARTED TOH
UP.
SOME LARGE SCALE STUDIES
CONDUCTED BECAUSE OF THESE
BIOBANKS, UK BIOBANK, BIG
STUDIES THAT HAVE A LOT OF THIS
DATA, BROAD CONSENT ALLOWED THIS
TO HAPPEN THE A SCALE.
THESE DATASETS ARE COMMON TO O
OUR -- WHICH IS GREAT BUT HERE'S
THE CHALLENGE.
THERE ARE SHARED SIGNALS WITH
THINGS LIKE DIABETES AND
GESTATIONAL DIABETES BUT THEY'RE
ALSO VERY DISTINCT AT THE SAME
TIME.
THE TISSUES INVOLVED IN SOME OF
THESE TRAITS ARE VERY DIFFERENT.
YOU CAN SEE RIGHT HERE THE
TISSUES INVOLVED IN TYPE
2 DIABETES ARE INCREDIBLY
DIFFERENT THAN THE TISSUES
INVOLVED IN GDM.
IT APPEARS THIS IS A LOT OF
CELL-SPECIFIC TISSUE EXPRESSION
GOING ON IN THE BRAIN WHICH IS
NOT THE CASE FOR TYPE
2 DIABETES.
SO IT REQUIRES A LOT MORE
TISSUES AND EXPERIMENTS IN THESE
SPACES AS WELL.
SO WITH THAT, I DON'T SEE THAT
THERE'S A SINGLE RESOURCE FOR
THE COMMUNITY FOR THE GENETICS
AND GENOMICS OF PREGNANCY TRAITS
SO OUR GOAL WAS TO SEED A
RESOURCE AND THE IDEA TO
INTEGRATE DATA AND INCREASE
POWER FOR DISCOVERY FOR
DIFFERENT THERAPEUTICS,
DIFFERENT TREATMENTS AND
DIFFERENT LOCI ASSOCIATED WITH
THESE PREGNANCY TRAITS.
SO WITH THAT, WE STARTED TO LOOK
FOR EXPERTS IN OUR FIELD AND WE
HAD A LITTLE COMMUNITY PUSH, WE
HAVE A COLLEAGUE NAMED JOHN
PERIWHO JASON AND I WORKED WITH
MANY YEARS AGO IN THE TYPE
2 DIABETES SPACE AND HE WORKED
WITH REPRO GEN, AND HE WAS LIKE
YEP, I WILL DO MY BEST AS ONE
PERSON REPRESENTING THIS
CONSORTIUM TO HELP YOU SEED A
RESOURCE.
SO WE WORKED WITH HIM TO
GENERATE A LIST OF SPECIFIC
TRAITS, CHALLENGES FOR THAT
FIELD, AND JASON IS GOING TO
TELL YOU A LITTLE ABOUT THAT
RESOURCE AND HOW YOU CAN VIEW
SOME OF THE INDIVIDUALIZATIONS
AND SOME OF THE FEATURES I
MENTIONED TO YOU EARLIER IN THE
CONTEXT OF THE REPRODUCTIVE
KNOWLEDGE PORTAL.
>> IN THE LIMITED TIME WE HAVE
TODAY, I FIGURED I CAN QI GIVE U
AN OVERVIEW OF THE RESOURCE, THE
CORE PHILOSOPHY BEHIND IT.
SO AS NOEL MENTIONED, THESE ARE
THE TRAITS THAT WE CURRENTLY
HAVE IN THE PORTAL.
THERE ARE ABOUT 37 OF THEM, AND
THESE ARE MOSTLY CURATED IN
COLLABORATION WITH THIS
COMMUNITY THAT WE WORKED WITH
AND A LOT OF THEM ARE A LITTLE
ESOTERIC AND PROBABLY MORE
SPECIALIZED THAN YOU WOULD SEE
IN A GENERAL RESOURCE, PROBABLY
A LOT OF THESE YOU WOULDN'T PUT
IN THE HIGHLY METABOLIC DISEASES
PORTAL, THAT'S KIND OF ONE OF
THE VALUES OF REALLY A DEDICATED
COMMUNITY RESOURCE.
WE ALSO HAVE -- I DON'T THINK WE
HAVE ANY SPECIFIC EP -- AS WELS
MANY OF THE OTHERS WE'VE CURATED
FOR METABOLIC DISEASES BUT THEY
COULD DEFINITELY BE IN THE AREA
WHERE WE THINK FOCUSED
AGGREGATION OF DATA AND TISSUES
RELEVANT TO THESE TRAITS COULD
BE VALUABLE.
OKAY.
SO AS NOEL MENTIONED, THE REAL
CORE PHILOSOPHY OR VALUE OUT OF
THIS PLATFORM IS TAKING THESE
COMPLICATED METHODS THAT PEOPLE
ARE NOW ROUTINELY RUNNING ACROSS
GENETIC ASSOCIATION STUDIES BUT
REQUIRES A LOT OF EXPERTISE TO
DO AND MAKING IT MUCH EASIER FOR
THEM TO ACCESS THE RESULTS BY
KIND OF POWERING THOSE OURSEL
OURSELVES.
SO THIS IS THE HOME PAGE TO THE
PORTAL.
I THINK IT'S AT REPRODUCT
REPRODUCTIVE.HUGEAMP.ORG IF YOU
WANT TO FOLLOW ALONG OR EXPLORE
IT YOURSELF.
OKAY.
NOW, THE KEY CONSTRUCT THAT
UNDERLIES THIS CONSTRUCT OF
MAKING SIMPLE VISUALIZATIONS IS
WHAT WE CALL A DATA SUMMARY.
SO THIS IS REALLY ANY STATISTIC
OR REALLY ANYTHING THAT COULD BE
COMPUTED FOR POTENTIALLY
SENSITIVE OR DATA YOU DON'T WANT
TO MAKE AVAILABLE TO THE PUBLIC.
THERE'S THREE COMPONENTS TO THAT
IN THIS PLATFORM.
WE CALL THE AGGREGATOR, IT'S
LIKE A PLATFORM WE'VE DEVELOPED
THAT USED SPARK TO ORCHESTRATE
COMPOUND WORK FLOWS THAT CAN RUN
A LOT OF COMPLICATED METHODS.
THE RESULTS ARE THEN STREAMED
OVER REST DIRECTLY FROM S3 USING
CUSTOM SOFTWARE AND THEN THERE'S
A LOT OF DEDICATED
VISUALIZATIONS WE'VE BUILT TO
MAKE THESE SUMMARIES EASY TO
VISUALIZE AND SEARCH AND BROWSE,
AND THAT'S WHAT YOU SEE ON THIS
PORTAL.
THE PAGE I'M JUST GOING TO WALK
THROUGH IS THE PHENOTYPE PAGE.
FROM THE HOME PAGE, YOU TYPE IN
A PHENOTYPE, YOU'LL GET ACCESS
TO THIS AND I THINK THE ONE I
CHOSE IS PREECLAMPSIA BECAUSE
SOME OF THEM DON'T HAVE A TON OF
SIGNALS.
THERE ARE A BUNCH OF OTHER
PAGES, YOU CAN SEARCH BY GENE,
THERE'S SOME TOOLS ON THE TOP WE
CAN TALK ABOUT THAT LATER OR
PLEASE COME UP TO US IF YOU'RE
INTERESTED.
BUT I JUST WANT TO ILLUSTRATE
HOW THIS KIND OF SHOWS THE
VARIOUS TYPES OF SUMMARIES AND
THE POWER THAT YOU CAN DO.
ALL OF THESE ARE AVAILABLE NOT
EVEN WITH A CLICK, YOU JUST
SCROLL DOWN THE PAGE AND YOU'LL
SEE ALL OF THESE ON THE PAGE.
SO THE SIMPLEST TYPE OF SUMMARY
IS BASIC AGGREGATION OF DATA.
SO THIS ESSENTIALLY BOILS DOWN
THE 5 MILLION OR SO SNPs
YOU'LL HAVE IN A GWAS TO THE
SIGNIFICANT SIGNAL.
SO THAT FIGURE THAT NOEL SHOWED,
THESE ARE THE INDEPENDENT
ASSOCIATIONS AT A GLANCE WHICH
IS USING A METHOD THAT'S VERY
SIMPLE TO APPLY BUT IT'S ALL
DONE FOR THE USER.
ANOTHER TYPE OF SUMMARY THAT IS
A LITTLE DIFFERENT IS NOT
ACTUALLY APPLYING -- ACTUALLY --
SORRY, LET ME -- I THINK SOMEONE
ELSE IS ADVANCING THE SLIDES.
IS THAT TRUE?
SO CAN YOU GO AHEAD TO SUMMARY
TYPE 4?
ONE MORE.
SO A SECOND TYPE OF SUMMARY IS
ACTUALLY NOT SOMETHING THAT
WE -- SOMETHING THAT WE CURATE.
THIS IS AN EXAMPLE OF HER GOING
THROUGH ALL OF THE PAPERS THAT
HAVE PUBLISHED THESE GWASs AND
EXTRACTING LISTS OF GENES THAT
PEOPLE -- THE AUTHORS HAVE
PUBLISHED THAT THEY THINK ARE
MEDIATING THE SIGNAL.
SO THAT'S VERY COMPLICATED, IT'S
NOT SOMETHING THAT CAN BE DONE
AUTOMATICALLY, BUT WE MAKE AN
EFFORT TO TRY TO CURATE THOSE AS
MUCH AS POSSIBLE.
I DON'T THINK WE HAVE ANY YET
FOR THE REPRODUCTIVE TRAITS
BECAUSE I DON'T THINK ANY ARE
AVAILABLE, BUT THAT'S SOMETHING
WE WORK ON DOING.
CAN WE GO BACK TO SUMMARY TYPE
2, PLEASE?
OKAY.
SO NOW THIS IS WHERE IT STARTS
TO GET A LITTLE MORE COMPLEX.
SO THIS IS A STATISTICAL METHOD,
VERY NON-TRIVIAL, THAT LOOKS AT
PREDEFINED PATHWAYS AND LOOKS
WHETHER GENES IN THOSE PATHWA
PATHWAYS -- IT'S SOMETHING
RELATIVELY STRAIGHTFORWARD TO
RUN BUT WE CAN APPLY THIS
AUTOMATICALLY ACROSS EVERY TRAIT
SO ANY GWAS WE UPLOAD INTO THE
SYSTEM GETS THESE RESULTS
APPLIED.
SO GOING A LITTLE BIT FURTHER,
YOU CAN ALSO APLAY ME NODS NOT
JUST TO THE UPLOADED GWAS BUT
INTEGRATED ACROSS MULTIPLE
DATASETS IN THE RESOURCE.
SO THIS NOW SCANS FOR THIS
PREECLAMPSIA GWAS FOR
CORRELATIONS BETWEEN IT AND ALL
OF THE THOUSAND OTHER TRAITS
THAT WE HAVE IN THAT PLATFORM.
SO YOU CAN SEE THAT GESTATIONAL
HYPERTENSION IS STRONGLY
CORRELATED, HEIGHT IS NEGATIVE
CORRELATED.
SOME OF THESE TRAITS ARE
SPECIFIC TO THE REPRODUCTIVE
KNOWLEDGE PORTAL, OTHERS ARE NOT
SPECIFIC BUT OBVIOUSLY MAKE
SENSE.
A CLOSE COUSIN OF THIS METHOD
LOOKS NOT JUST AT THE GENETIC
DATA BUT THE EPIGENOMIC DATA AND
CAN FIND TISSUES IN WHICH
ASSOCIATIONS ARE ACTIVE AND OPEN
CHROMATIN.
SO PLACENTA IS THE STRONGEST
TISSUE, PLACENTA ENHANCERS
SPECIFICALLY ARE MOST ENRICHED
FOR THIS TRAIT.
AND FINALLY, THE LAST BIT IS
THAT WHAT WE THEN DO IS WE
FINALLY IDENTIFY GAPS IN
EXISTING METHODS.
IN THIS CASE THIS WAS A GAP FOR
GENETIC SUPPORT, WE HAD PHARMA
PARTNERS VERY INTERESTED IN --
IS THERE ANY EVIDENCE AT ALL
THAT THERE'S AN ASSOCIATION, SO
WE DEVELOPED OUR OWN METHOD AND
PUBLISHED THIS I THINK A COUPLE
YEARS AGO AND NOW THAT IS
APPLIED TO EVERY TRAIT AS WELL.
THE THING I WANT TO CONCLUDE
WITH, RIGHT NOW ALL OF THIS IS
GENOMICS BUT AS WE'VE KIND OF
STARTED TO THINK BEYOND THAT, I
THINK THE KEY GAP OR REALLY NEED
IN NOT JUST THIS FIELD BUT MANY
IS THAT A LOT OF THESE
REPOSITORIES AND DATASETS ARE
NOT EASILY ACCESSIBLE TO PEOPLE,
AND MEANL TIMES ONCE YOU GET
INTO THE SYSTEM IT'S VESTIBLE
BUT PEOPLE ARE BUSY, SOMETIMES
YOU CAN SAY OH, I'LL ADD THAT TO
MY TO-DO LIST AND THEN NEVER GET
TO IT.
SO I THINK THERE'S VALUE IN THIS
ALMOST AS AN ENTRY POINT THAT
YOU WORK WITH THE COMMUNITIES TO
UNDERSTAND WHAT'S VALUABLE DATA
IN THERE, AND THEN YOU WORK TO
DEFINE HOW TO PULL IT OUT AND
MAKE VERY EASY TO ACCESS ENTRY
POINTS FOR THE USER.
AND THAT'S REALLY WHAT I THINK
IS NEEDED IN A LOT OF THESE
AREAS.
SO IF YOU GO TO THE NEXT SLIDE,
SO THESE WORK SPACES, WHICH, YOU
KNOW, HAVE EVERYTHING YOU EVER
NEED BUT ARE VERY IMPENETRABLE
TO ME COMING OUT TO -- I DON'T
KNOW WHAT RADIANT CLIA WGS IS
HERE, NOW I DO AFTER SPENDING
HALF AN HOUR DOING IT, BUT I
SPENT SIX MONTHS LEARNING IT, IT
WAS CRYPTIC TO ME.
THIS IS FOR THE COMMON FUND DATA
ECOSYSTEM WE ARE WORKING ON AND
THEY IS HOW THEY SUMMARIZE THE
DATA THAT'S AVAILABLE.
IT'S THROUGH THESE TERMS LIKE
ALIGNMENT, SEQUENCE AND MATRIX.
I HAD A QUESTION, LIKE HOW MUCH
SINGLE CELL ATTACK ATAC SEQ DOE
IN THE PANCREAS?
YOU ALSO NEED SOMETHING LIKE --
THIS IS JUST A FIRST VERSION,
BUT SOMETHING THAT THINKS ABOUT
WHAT'S THE RESEARCHER'S CONTEXT,
WHAT IS THE TYPES OF THINGS
THEY'RE INTERESTED IN AND CAN WE
PULL THAT OUT TO THEM SO THAT
THEN THEY CAN GET IN MORE EASY
TO ENTER POINT THAT THEN MAYBE
ONCE THEY'RE IN, NOW YOU HAVE
THEM HOOKED AND NOW THEY CAN
NAVIGATE TO GET THE FULL VALUE
OF YOUR SYSTEM.
THAT'S SOMETHING I THINK IS
OFTEN UNDERAPPRECIATED, THIS
CONCEPT THAT EVEN IF IT'S EASY
TO YOU OR EASY ONCE THEY EVEN
INVEST AN HOUR, WE'RE ALL BUSY
AND SOMETIMES NEED SOMETHING
THAT THEY CAN DO IN 30 SECONDS.
SO ON THE FINAL SLIDE JUST TO
ACKNOWLEDGE ALL THE PEOPLE WHO
HAVE BUILT THIS, BOTH AT THE
BROAD AND OUR OTHER COLLEAGUES
AS PART OF AMP C & D AND THANK
YOU ALL FOR INVITING US AND
LOOKING FORWARD TO LEARNING MORE
ABOUT THIS COMMUNITY.
THANK YOU.
>> WE HAVE ABOUT 8 MINUTES LEFT
FOR ANY QUESTIONS.
FROM THE AUDIENCE.
IF THE SPEAKERS HAVE ANY TOPICS
TO DISCUSS, I'M OPENING UP THE
FLOOR.
>> THIS IS MORE OF A THOUGHT
THAN A QUESTION BUT I'M NOT SURE
HOW TO PHRASE THIS, BUT AS I WAS
LISTENING TO THESE TALKS, AND
ESPECIALLY IN REGARDS TO THE
BIOREPOSITORIES, ONE THING THAT
I WAS REALLY THINKING ABOUT,
THERE'S OBVIOUSLY MANY DIFFERENT
BIOREPOSITORIES.
ONE COULD ARGUE WE NEED MORE.
THERE ARE TWO MODELS.
ONE WHICH IS WELL, LET'S BUILD
ONE GIGANTIC HUGE BIOREPOSITORY
THAT GOVERNMENT CONTROLS.
I DON'T KNOW IF THAT'S THE BEST
WAY TO GO.
BUT WE ALSO NEED TO BE ABLE TO
GET SAMPLES ACROSS A LOT OF
BIOREPOSITORIES AS SORT OF THE
FEDERATED MODEL FOR DATA SORT OF
COMES TO MIND, IT WAS COMING TO
MIND WHEN I THOUGHT ABOUT THAT.
DOES ANYBODY -- HAS ANYBODY
THOUGHT OR ARE THERE EXAMPLES OR
DOES ANYBODY HAVE ANY THOUGHTS
ON SORT OF HOW ONE COULD CREATE
A FEDERATED ECOSYSTEM FOR
BIOSAMPLES, IF SOMEBODY WANTED
TO GO, OH, I'M GOING TO DO THIS
STUDY AND THIS SUBTYPE OF
PREECLAMPSIA, NOW I CAN SEARCH
FOR IT AND FIND ALL THE
BIOSAMPLES.
SOMETHING LIKE THAT.
>> WE'RE INVOLVED IN ONE EXAMPLE
OF THAT IN A SMALL MICROCHASM,
SOMEWHAT SMALL MICROCHASM OF
PREECLAMPSIA AND THAT'S THE
COLAB GROUP, ORIGINALLY FUNDED
BY THE GATES FOUNDATION, AND IT
WAS LED BY LES MYATT AND JIM
ROBERTS AND MCGEE, AND THEY
WORKED TO GET A WHOLE BUNCH OF
PEOPLE INTERNATIONALLY TO SHARE
CLINICAL DATA AND SAMPLES, AND
SO THEY WORKED TO HAVE SOME KIND
OF DATA STRUCTURE AND IT'S NOT
AS SOPHISTICATED AS WHAT MY
COLLEAGUES HERE HAVE ALREADY
TALKED ABOUT BUT THAT WAS ONE
STEP AND THERE WAS A WHITE PAPER
ABOUT IT AT A BIG NIH WORKSHOP
ABOUT TRYING TO COLLECT THE
DATA, BUT THEN ALSO HAVING A
SORT OF FORMAL PRO SELLS, SO PRO
INTERNATIONALLY WITH THEIR
MEETINGS, ZOOM MEETINGS THANK
GOD, THAT PEOPLE WILL APPLY FOR
SAMPLES AND THEN THERE'S SORT OF
A GENERAL CALLOUT WHO'S GOT
THIS, AND THEN PEOPLE WITH THE
APPROPRIATE DATABASES OR
BIOREPOSITORIES KIND OF PIPE UP
AND THEN SHARE ACCORDINGLY, AND
THEN INDIVIDUALLY, AND THIS IS
THE HARD PART, IS INDIVIDUALLY
PEOPLE WORK OUT THEIR OWN
SPECIFIC SORT OF DATA OR
BIOSAMPLE SHARING AGREEMENTS.
AND SO THAT'S -- AS WE MOVE
FORWARD, THIS SORT OF GOVERNANCE
IS WHAT WE'RE GOING TO HAVE TO
ACTUALLY START THINKING ABOUT.
>> WHAT I FOUND IS THE
CHALLENGE, FOR OUR REPOSITORY,
WE CAN FOLLOW LONG TERM HEALTH
OF THE MOM AND THE CHILD, SO
WHEN YOU HAVE SOMETHING LIKE A
REDCAP DATABASE WHERE YOU'RE
JUST EXTRACTING WHAT HAPPENED UP
UNTIL DELIVERY OR A LITTLE BIT
AFTERWARDS, THAT DOESN'T REALLY
ALLOW FOR THE LONG TERM
FOLLOW-UP AND SO FOR US, TERRING
ENTERING DATA INTO SOMETHING
LIKE THAT WOULD BE TOO
CUMBERSOME AND WOULD TAKE TIME
GOING BACK.
IN THE IHK, WE GO IN AND DO IT
AUTOMATICALLY AND DON'T HAVE TO
EXTRACT INFORMATION ON EACH OF
ARE OUR PARTICIPANTS BECAUSE WE
CAN JUST GO QUERY FOR IT WHEN WE
NEED IT.
SO THERE NEEDS TO BE SOME MORE
OF AN AUTOMATED WAY TO KEEP
DOING IT.
IT WAS HARD FOR US TO ENTER HOW
MANY PEOPLE WE HAVE IN THE IU
SYSTEM BECAUSE WE KEEP
ENROLLING, IT'S NOT A SET SYSTEM
SO IT'S HARD FOR ME TO ANSWER
WHAT WE HAVE BECAUSE WE KEEP
GETTING SAMPLES AND DATA.
>> SO THE NCI HAS A COUPLE OF
MODELS THAT MIGHT SUIT OR MIGHT
BE SOMETHING TO LOOK AT FOR YOUR
QUESTION.
THERE'S SOMETHING CALLED
SPECIMEN CENTRAL WHICH IS MEANT
TO BE AN AGGREGATION OF ALL THE
BIOBANKS OUT THERE FOR CANCER.
I DON'T KNOW HOW WELL IT'S USED
AND I DON'T KNOW HOW WELL IT'S
CURATING, BUT I DO KNOW THAT IT
EXISTS.
WE ALSO HAVE THE COOPERATIVE
HUMAN TISSUE NETWORK, WHICH IS A
PROSPECTIVE COLLECTION NETWORK.
IT IS FUNDED BY THE NCI, AND
THERE ARE MULTIPLE SITES WHICH
ARE CONTRACTED TO PROVIDE
SAMPLES TO INVESTIGATORS WHO ARE
ASKING FOR THEM.
SO IF YOU'RE LOOKING FOR GYN ONC
SAMPLES, YOU CAN SOLICIT ACROSS
THIS NETWORK AND SEE WHO'S GOT
SAMPLES AND THEY COULD BE
PROSPECTIVELY COLLECTED OR THEY
MIGHT BE IN THE BIOBANK.
THE CENTRAL BIOREPOSITORY AT THE
UNIVERSITY OF MICHIGAN WAS MEANT
TO ADDRESS PART OF YOUR
QUESTION.
WE HAD A BIG QUESTION ABOUT DO
WE WANT TO FED RATE IT, DO WE
WANT TO CENTRALIZE IT IN ONE
INFRASTRUCTURE.
WE OPTED FOR THE 1 CENTRALIZATIN
BECAUSE IT WAS EASIER TO MANAGE
THE QUALITY OF THE BIOSPECIMENS
AND THE PROCESS OF THE STANDARD
OPERATING PROCEDURES.
BUT WE TRIED TO -- THE REASON
WHY WE HAVE SO MANY BIOBANKS
THAT ARE INCORPORATED INTO IT
WAS SO THAT WE COULD GET A WIDE
SWATH OF SAMPLES WITH THE EHR
DATA AND ANY INVESTIGATOR AT THE
UNIVERSITY OF MICHIGAN WITH
PERMISSION CAN INVESTIGATE
WHETHER OR NOT THE SAMPLES THAT
THEY'RE LOOKING FOR ARE IN OUR
BIOBANK.
>> QUESTION TO THE HUGEAMP
PROJECT.
TWO QUESTIONS.
NUMBER ONE IS, SO THERE ARE A
NUMBER OF PUBLICATIONS, THEY
ACTUALLY PUBLISHED META-ANALYSIS
ALREADY, SO IS THE KNOWLEDGE
BASIN TENSIONALLY COLLECTING
THOSE DATA AS WELL?
OKAY, GOOD.
>> IN FACT THAT'S THE MAJORITY
OF THE DATASETS WE HAVE, ARE
META-ANALYSIS, FOR SURE.
THOSE ARE MOST POWERFUL TO GET
AND EASIER TO GET -- FOR SURE.
>> MUCH CHEAPER.
AND THEN ABOUT THE DATA, I THINK
JASON ACTUALLY TALKED ABOUT THE
GWAS DATA, WHAT ABOUT THE OMICS,
LIKE TRANSCRIPTOMICS OR
PROTEOMICS, ARE YOU ALSO DOING
THOSE ANALYSES AS WELL?
>> YEAH, SO AT THE MOMENT, THE
WAY THAT THOSE ARE MOSTLY
HANDLED ARE EPIGENOMIC AN
ANNOTATIONS OF THE GENOME, AND
THE TRANSCRIPTOMIC IS SOMETHING
WE'RE JUST TACKLING NOW.
BASED ON THE ORIGINAL FOCUS ON
GENETICS, WE'VE ALWAYS BEEN
TRYING TO THINK ABOUT HOW DO YOU
CONNECT THAT TO THE GENETICS BUT
NOW WE'RE RE REALIZING THERE'S
VALUE -- WE'RE STARTING WITH
DIFFERENTIAL TYPE ANALYSES BUT
AGAIN APPLYING THE SAME
PHILOSOPHY.
>> HOW BIG A PREECLAMPSIA
GENOMICS STUDY YOU HAVE SO FAR?
>> THE GWAS STUDY WE HAVE?
>> YEAH.
>> I DON'T KNOW, IT'S PROBABLY
100 OR 200,000 PEOPLE, WHATEVER
THE BIGGEST ONE IS.
>> I HAD ONE QUICK QUESTION
WHICH WAS I THINK A LOT OF THE
CHALLENGES DISCUSSED INCLUDED
BEING RELIANT ON FUNDING CYCLES
AND HAVING TO START AND STOP
RECRUITMENT, BUT SOME SEEMED
LIKE THEY HAD A SELF STAINED
MODEL.
I WAS CURIOUS TO KNOW, WHAT
REALLY HELPS YOU HAVE A
SELF-SUSTAINING MODEL FOR
BIOBANKING?
IS IT INSTITUTIONAL DEVELOPMENTS
OR WHAT ARE THE THINGS YOU HAVE?
>> WE HAVE SOME INSTITUTIONAL
INVESTMENTS BUT WE ARE ALSO
VERY, VERY CHEAP.
WE JUST RUN FRUGALLY AS WE CAN,
WE GO ON AS MANY GRANTS AS WE
CAN.
THE BENEFIT TO THE UNIVERSITY OF
IOWA IS THAT WE HAVE
UNDERGRADUATES SO THEY ACTUALLY
ARE VERY HELPFUL TO RUNNING THE
LAB, LEARN HOW TO CONSENT, LEARN
HOW TO PROCESS SAMPLES, AND THEN
WE HAVE ADULT SCIENTISTS OVER
THEM.
THAT OVERSEE.
>> IT'S A VERY HYBRID MODEL.
YOU KNOW, A LOT OF IT IS -- IT
STARTED OFF BY AN INVESTMENT BY
OUR CHAIR AND THEN OUR COLLEGE
AND THEN IT WAS ALL OF OUR
GRANTS.
THIS -- WE ARE NOT A CORE, SO WE
DON'T SELL DATA OR SAMPLES.
EVERYTHING IS A COLLABORATION,
AND SO IT'S A LITTLE BIT --
DONNA AND I OFTEN TEASE THAT
WE'RE KIND OF THE BIOSAMPLE
DATA, YOU KNOW, LIKE LET ME GET
YOU YOUR FIRST SET AND ONCE YOU
GET ADDICTED TO WHAT YOU NEED
AND GET YOUR PRELIMINARY DATA,
WE GET YOU TO -- WE GO TOGETHER
IN THE NEXT STEP, WHETHER THAT'S
A PAPER OR A GRANT.
>> I THINK WE'RE ON THE OTHER
END OF THE SPECTRUM FOR THAT.
I THINK IT'S INSTITUTIONAL
SUPPORT FOR ANY OF THE GAPS IN
FUNDING BUT THEN A LOT OF IT IS
WE ARE A CORE AND SAMPLES ARE
PRICED PER SAMPLE, BUT
INTERNALLY, THAT ENDS UP BEING
VERY, VERY AFFORDABLE TO ANY OF
OUR RESEARCHERS, AND THEN SOME
OF THEM ARE STILL PROSPECTIVELY
COLLECTED BASED ON NIH FUNDING
AND THEN WE TAKE OVER ONCE THOSE
FUNDS RUN OUT, THEN IT'S AN
INSTITUTIONAL SUPPORT.
>> I OVERSEE A PROGRAM IN THE
INNOVATIVE MEDICINES INITIATIVE
IN EUROPE, SO IT'S 28 COUNTRIES,
18 DIFFERENT REPOSITORIES, AND
WE HAVE DEVELOPED A FEDERATED
MODEL BECAUSE WE HAD TO, BECAUSE
YOU CAN'T PULL THE DATA OUT OF
NORDIC COUNTRIES AND YOU CAN'T
PULL THE SAMPLES OUT OF THE
NORDIC COUNTRIES, BUT -- AND WE
USE A KNOWLEDGE GRAPH TO
ACTUALLY REPRESENT WHAT THE
OVERALL STRUCTURE WOULD LOOK
LIKE BASED ON A MODEL OF
DEVELOPMENT AND DISEASE, BUT THE
CHALLENGE THAT YOU ALSO HAVE, I
DON'T KNOW THAT ANYONE HAS
REALLY ADDRESSED, WHILE YOU'RE
LOOKING AT COMMON DATA ELEMENTS,
AND USING THAT AS SORT OF AN
INTEGRATION, INTRAINSTITUTIONAL
AND INTERINSTITUTIONAL, THE DATA
ELEMENT LABEL DOESN'T
NECESSARILY MEAN THE SAME THING,
AND SO WE'VE HAD TO SET UP AN
ENTIRE STRUCTURE SEPARATELY TO
BE ABLE TO ANNOTATE WHAT THAT
MEANS FROM EACH OF THE
INSTITUTIONS BECAUSE IT TESTS
FOR HER-2 -- IS NOT THE SAME IN
ONE INSTITUTION AS IT IS IN
ANOTHER, THE THRESHOLDS MAY NOT
BE THE SAME AS WELL AS THE TEST.
AND IF YOU DON'T TRACK THAT AND
THEN TRY TO USE THAT AS A BIG
DATA MODEL, IT CAUSES A LOT OF
PROBLEMS DOWNSTREAM.
I WONDERED HOW YOU'RE DEALING
WITH THAT.
>> WELL, THOSE ARE LIKE THE NEXT
STEPS AT LEAST FOR THE IHK,
TRYING TO MOVE TO THOSE COMMON
DATA ELEMENTS IN OMOP SO AT
LEAST WE CAN HAVE SOME
INTRAOPERABILITY BECAUSE WHAT WE
RUN INTO IS WE ARE TRYING TO GET
DATA FROM A COMPLETELY DIFFERENT
EHR.
BUT SOME OF THAT IS FIREABLE AND
OMOPABLE, THAT'S A TERM, SO
THESE ARE THINGS THAT WE HAVE
THIS SORT OF COMMON LANGUAGE
THAT OUR BMI FOLKS ARE WORKING
ON OUR -- OUR INFORMATICS FOLKS
ARE WORKING ON AND THAT'S SORT
OF OUR NEXT PHASE OF THE
INTERGENERATIONAL HEALTH
KNOWLEDGE BASE.
>> SO THAT, I THINK, IS REALLY
CRITICAL, BECAUSE WE ARE NOT
PULLING DATA OUT OF NORWAY.
WE ARE ONE COUNTRY AND WE SHOULD
BE ABLE TO SHARE DATA.
IF WE WANT TO HAVE A SHOT AT
FULLING TPULLING THESE SAMPLES R
AND ANALYZING THEM CENTRALLY,
SENDING AROUND EXCEL
SPREADSHEETS AND REDCAP -- TO GO
WITH THE SAMPLES IS REALLY
DIMINISHING THE VALUE OF THE
TENS OF THOUSANDS OF DOLLARS
THAT WE ARE GOING TO SPEND PER
SAMPLE TO RUN COMPLEX
MULTI-OMICS STUDIES ON.
IF WE CAN DO COMPLEX -- WE CAN
FIGURE OUT HOW TO SHARE EHR DATA
BETWEEN -- AND EPIC, OTHER
PEOPLE HAVE ALREADY DONE THAT, I
WAS DELIGHTED TO SEE THE
HL7 STANDARD.
IF WE CAN'T SHARE -- DATA, I
THINK THAT'S JUST A CONVERSATION
STOPPER.
THERE'S NO REASON TO SHARE
SAMPLES IF YOU CAN'T SHARE THE
DATA WITH IT.
>> PART OF THAT SPHIXING THE
MEDICAL RECORD.
WE SPENT A LOT OF TIME CHANGING
THE NOTES WHICH HAD TO BE THE
FIRST STEP SO THERE WERE MORE
DISCRETE FIELDS.
SOME OF OUR NOTES LOOK LIKE
DISCRETE FIELDS BUT THEY'RE NOT,
THEY'RE JUST TEMPLATES, SO
ACTUALLY HAVING MORE DISCRETE
FIELDS MADE IT -- TO PULL THINGS
OUT AUTOMATICALLY.
>> OF COURSE.
I AGREE WITH YOUR EARLIER
COMMENT THAT IF YOU ASK ME TO
FILL REDCAP FORMS I'M JUST NOT
GOING TO HAVE THE MANPOWER TO DO
IT.
ON THE OTHER END, AS A DATA
SCIENTIST, I DON'T WANT THE
REDCAP FORM, I WANT THE REAL
DATA.
WE ARE ALL THE SAME --
>> I'M SORRY, I CAN'T READ YOUR
NAME, YOU'VE BEEN WAITING TO ASK
FOR A WHILE NOW.
>> I'M FROM NATIONWIDE
CHILDREN'S HOSPITAL.
I HAVE QUESTIONS ON THE BIOBANK
SAMPLE.
I'M NOT SURE WHETHER THERE'S A
BIOBANK INTRODUCED AT WASHINGTON
UNIVERSITY, UNIVERSITY OF
MICHIGAN -- IOWA, SO ARE YOUR
BIOBANKS SUPPORTED -- AND IF NOT
SUPPORTED, HOW CAN YOU MAINTAIN
THE BIOBANKS AT THE SAME TIME
CAN I GET THE SAMPLE FROM YOUR
BIOBANK IN TERMS OF -- THANK
YOU.
>> YES TO ALL OF THE QUESTIONS.
SO WE ARE -- THE EP CENTRAL
BIOREPOSITORY IS A CORE
STRUCTURE, WE ARE A RECHARGE
OPERATION.
MANY OF THE FOLKS WHO ARE USING
THE BIOBANK ARE FUNDED BY NIH.
WE HAVE SEVERAL COLLECTIONS THAT
ARE SPECIFICALLY FUNDED BY NIH
AND THE SAMPLES ARE AVAILABLE
FOR EXTRAMURAL USE.
IF THEY'RE FUNDED THROUGH THE
NIH, THEN YOU GO THROUGH THE NIH
STEERING COMMITTEE, IF THEY'RE
FUNDED THROUGH THE UNIVERSITY OF
MICHIGAN OR ON A GRANT THAT IS
HOUSED AT UNIVERSITY OF
MICHIGAN, THEN YOU GO THROUGH
OUR PROCEDURES AND I CAN TALK
WITH YOU AFTERWARDS.
>> IN THE INTEREST OF TIME WE'LL
TAKE ONE LAST QUESTION AND THEN
WRAP UP.
>> I JUST WANT TO BRING
EVERYTHING BASED ON THE HUGEAMP
PRESENTATION, SO I'M SURPRISED
THAT YOU CAN GET ON IN HALF AN
HOUR BECAUSE I AM THE DATA
SCIENTIST WHO SPENDS WEEKS
TRYING TO GET ON THE
DIFFERENT -- EVEN THE CFDE, ALL
THE DIFFERENT PARTS, BECAUSE
EVEN THOUGH IT'S THE COMMON
FUND, IT'S LIKE IN THE DIFFERENT
CONSORTIA.
BUT ONE THING THAT I THINK IS
REALLY DIFFICULT NOW IS THAT
SOME OF THE DATASETS END UP
BEING CLOSED, SO FOR EXAMPLE,
ALL-OF-US, YOU HAVE TO WORK ON
TERRA, SO THEN TRYING TO
INTEGRATE ALL OF THE ALL-OF-US
DATA WITH DATA, SAY, FROM OTHER
CONSORTIA OR FROM A GIVEN LAB, A
GIVEN LAB MAY WANT TO VALIDATE
THEIR RESULTS AGAINST ALL-OF-US,
THEN IT'S REALLY, REALLY HARD,
AND IT'S REALLY, REALLY
EXPENSIVE.
AND SO I GUESS IS THERE A PLAN,
BECAUSE DIFFERENT NIH INSTITUTES
HAVE THEIR FAVORITE ENVIRONMENT,
RIGHT?
LIKE THERE'S SCIVATICA TOO.
SO HOW ARE WE SUPPOSED TO BRIDGE
THROUGH WHEN WE'RE REALLY TRYING
TO LEVERAGE MULTI-OMICS DATA --
YOU MAY EVEN WANT ATAC SEQ FROM
PANCREAS BUT IT MIGHT BE LIVING
IN LIKE 15 DIFFERENT PLACES.
>> YOU CAN GO AHEAD.
>> I THINK THAT'S A REALLY HARD
QUESTION ABOUT GETTING ASSAYS ON
UNDERLYING DATA.
THAT'S BEYOND THE SCOPE PROBABLY
OF HERE WE COULD ANSWER, BUT I
WOULD SAY THAT IF YOU CAN DEFINE
AN ANALYSIS UP FRONT THAT YOU
WANT TO DO, MORE
HYPOTHESIS-DRIVEN OR QUESTION
RESEARCH, I THINK THAT IS AN
EASIER PROBLEM TO SOLVE AND
THAT'S KIND OF WHERE WE COME IN,
IF THAT MAKES SENSE.
IF YOU'RE LIKE I WANT TO
VALIDATE WHETHER THIS SPECIFIC
GENE HAS ASSOCIATIONS ACROSS THE
DATA, THAT SEEMS LIKE IT CAN BE
SOLVED MUCH MORE QUICKLY THAN
HOW DO I SE CENTRALIZE -- HOW DI
GET ALL THE DATA IN ONE PLACE I
CAN ANALYZE, IF THAT MAKES
SENSE.
THAT IS A MUCH TOUGHER --
>> SO WE'RE DOING SOMETHING
REALLY DUMB, SO WE WANT TO LOOK
AT THE DIFFERENCE BETWEEN MALE
AND FEMALE IN THREE DIFFERENT
TISSUE, BRAIN, HEART, LIVER, AND
WE WANT TO KNOW HOW THAT
OPERATES AT MULTI-SCALES.
THE TISSUE SCALE, AND THEN THE
CELLULAR SCALE, FOR EXAMPLE.
SO THERE'S SINGLE CELL DATA,
THERE'S BULK TISSUE DATA, ALL
KINDS OF DIFFERENT -- AND IT'S
REALLY HARD.
EVEN THAT REALLY DUMB QUESTION,
RIGHT, TO ASK, AND SO -- BUT
FIRST IF I WENT INTO IT, I WAS
LIKE OH, WE CAN JUST GO
SHOPPING.
THERE MUST BE A SHOPPING CART
YOU CAN SAY, I WANT DATA FROM
THESE TISSUES, USING THIS ASSAY,
AND THEN LOOK THROUGH THE COMMON
FUND.
YOU CAN'T -- THERE IS NO
SHOPPING CART.
>> SO THAT IS A PROBLEM FOR THE
COMMON FUND, THERE'S NEW DATA
RESOURCE CENTER AND KNOWLEDGE
CENTER THAT ARE TRYING TO MAKE
THAT GOING BEYOND THAT, I THINK
IS GOING TO BE HARDER, BUT I
THINK YOU -- LIKE HOW ODYSSEY
DOES IT, HOW YOU KIND OF DEFINE
YOUR ANALYSIS, YOU SUBMIT IT.
I THINK YOU COULD TACKLE THAT
PROBLEM OR YOU COULD MAYBE
DEFINE THAT ANALYSIS
SPECIFICALLY AND MAYBE MAKE THAT
LESS PAINFUL, BUT THAT'S
OBVIOUSLY A LOT OF WORK.
I DON'T KNOW IF YOU WANT TO ADD
TO IT.
>> I JUST THINK IT'S A
TWO-PRONGED PROBLEM.
IN MANY CASES, DO YOU WANT THE
INDIVIDUAL LEVEL DATA YOURSELF
OR DO YOU WANT THE RESULTS?
LIKE DO YOU WANT TO BE ABLE TO,
LIKE -- I THINK THAT'S WHEN THE
CHALLENGE IS BECAUSE YOU DON'T
WANT TO ACTUALLY HAVE ACCESS TO
EVERY SINGLE REPOSITORY TO
FIGURE OUT THE GYMNASTICS TO GET
AT THEM BUT YOU HAVE TO SPECIFIC
YOU WANT TO ASK, IS THAT
CORRECT?
>> WELL, SO THAT'S ACTUALLY --
SO I THINK THE SAME QUESTION OF
THE BIOREPOSITORY THAT ACTUALLY
IF YOU REALLY WANT TO TRUST YOUR
DATA, YOU WANT THAT NITTY
GRITTY, RIGHT?
YOU WANT THE ACCESS TO THE
CLINICAL DATA, SO YOU KNOW THAT
YOUR SAMPLE ACTUALLY HAS WHAT
YOU SAY IT HAS WHEN YOU'RE DOING
YOUR ANALYSIS.
SAME THING WHEN YOU'RE DOING DAY
DATA ANALYSIS, YOU WANT THAT RAW
DATA SO YOU CAN CONTROL ALL OF
THAT PREPROCESS NORMALIZATION,
CLEANING, UNDERSTANDING IF
THERE'S SOMETHING KOOKY, RIGHT,
YOU MAY END UP WITH SAMPLES FROM
A GIVEN SITE THAT'S WAY OUT
THERE IN YOUR ANALYSIS, YOU HAVE
ALL THAT UNDERLYING METADATA,
WHY IS THAT SITE DIFFERENT FROM
ALL THE OTHER SITES?
SHOULD I JUST SENSOR IT OR IS
THERE SOME WAY I CAN CORRECT --
SO I THINK THAT'S THE PROBLEM,
WE'RE TRYING TO OPERATE AND GET
THE BEST SCIENTIFIC RESULTS
POSSIBLE, HAVING SORT OF
INCOMPLETE FEELERS INTO THE
BACKGROUND OF OUR DATA.
>> I KNOW WE'RE OVER TIME BUT
JUST ONE COMMENT ON THAT BECAUSE
I THINK ONCE YOU START TO
CONCEPTUALIZE THAT RESEARCH
QUESTION NOT JUST AS A ONE SHOT
THING BUT A PROGRESSIVE LIKE
PUTTING FEELERS OUT AND
GRADUALLY INVESTING MORE, LIKE I
THINK THAT'S A MODEL A LOT OF US
HAVE IN OUR LABS.
YOU HAVE A BUNCH OF IDEAS, THEN
YOU'LL EVENTUALLY ASSIGN ONE TO
AN UNDERGRAD WHO COMES IN AND
THEN IF THEY HAVE GOOD
PRELIMINARY DATA, NOW YOU'LL
INVEST MORE RESOURCES.
SO I THINK THE WAY WE THINK
ABOUT IT IS, CAN WE PULL LIKE
THAT FIRST GLIMPSE AT IT SO
YOU'RE LIKE, AH, THAT ANALYSIS
NOW MAKES SENSE FOR ME TO GO
OBTAIN THE NITTY GRITTY DATA,
RIGHT?
SO NOW YOU LIKE KNOW -- YOU HAVE
ENOUGH THAT YOU'VE SEEN THAT YOU
NOW ARE NOT GOING IN BLIND AND
YOU'RE LIKE OKAY, I KNOW IT'S
GOING TO BE PAINFUL TO DO ALL
THIS STUFF BUT NOW IT'S WORTH IT
BECAUSE I AT LEAST HAVE SOME
PRELIMINARY DATA.
>> I GUESS OWSH IS OUR ISSUE ISR
DICER DOES THAT, THE SLICER
DICER IS SO SCREWED UP THAT IT
MAY TELL YOU THERE IS NO
QUESTION THERE WHEN THERE IS A
QUESTION, OR IT MAY TELL YOU
THERE IS SOMETHING THERE WHEN
IT'S JUST ARTIFACT, RIGHT?
SO I GUESS IT'S LIKE HOW DO WE
IMPROVE THAT LAYER.
>> WE CAN BE A LITTLE BIT
MORE -- THE ODYSSEY MODEL WHERE
EVERYBODY OPTS IN BASED ON THE
QUESTION.
BUT THE PARALLEL TO ODYSSEY IS
PETE'SNET WHERE THEY DO HAVE
EVERYTHING CENTRALLY IN ONE
PLACE, FRESH OUT OF THE EHR AND
YOU CAN ASK ANY QUESTION THAT
YOU WANT, I HOPE MAYBE NOT
IMMEDIATELY BUT ONE DAY WE CAN
GET TO PLACE WHERE THINGS ARE
ACCESSIBLE THE WAY YOU WANT THEM
TO BE, NOT IN ISOLATED PLACES.
>> OKAY.
WITH THAT, LET'S WRAP UP THIS
SESSION.
THANK YOU TO THE SPEAKERS FOR
SHARING YOUR EXCELLENT INSIGHTS
AND WORK.
ROUND OF APPLAUSE.
WE'RE ABLE TO TAKE A QUICK BREAK
AND REGROUP BY 11:10
>> GOOD MORNING.
I'M MELISSA JONES REYES, I'M
WITH THE FNH, MOVING SCIENCE
FORWARD WITH CURRENT AND
EMERGING RESEARCH AND DIAGNOSTIC
TECHNOLOGIES.
OUR FIRST SPEAKER WILL BE LOUIS
LAURENT FROM THE UNIVERSITY OF
CALIFORNIA SAN DIEGO.
>> I'M GOING TO TALK A LITTLE
BIT ABOUT TWO THINGS, KIND OF
COMING FROM MY GROUP, AND I
REALLY APPRECIATE THE
OPPORTUNITY TO PRESENT THESE
THINGS.
SO ONE IS ABOUT THE MULTI-OMICS
FOR HEALTH AND DISEASE
CONSORTIUM, WHICH MY GROUP IS
ONE OF THE DISEASE STUDY SITES
FOR.
WE'LL TALK A LITTLE BIT ABOUT
KIND OF THE OPPORTUNITIES AND
CHALLENGES OF WORKING WITH A
CONSORTIUM THAT CROSSES MANY
DIFFERENT TYPES OF DISEASE, OF
WHICH WE'RE THE ONLY
REPRODUCTIVE GROUP.
SO THE VISION OF THE MOHD CORE
SORE SHUM OVERALL IS TO ADVANCE
THE APPLICATION OF MULTI-OMICS
TO BOTH HEALTH AND DISEASE IN
MINORITY ANCESTRY POPULATIONS
THROUGH A HARMONIZED AND
INTEGRATED DATABASE MADE
AVAILABLE AS APPROPRIATE TO THE
PUBLIC AND RESEARCHERS.
AND WE HAVE SEVERAL PROGRAM
GOALS THAT WERE JOINTLY
CONSTRUCTED AMONG THE GROUPS.
ONE IS TO VALIDATE AND ENHANCE
GENERALIZABLE MULTI-OMICS
APPROACHES TO IDENTIFY
MEANINGFUL BIOLOGICAL CHANGES
RELATED TO HEALTH AND DISEASE.
THE SECOND IS TO EXPLORE THE USE
OF MULTI-OMICS TO DETECT AND
ASSESS MOLECULAR PROFILES
ASSOCIATED WITH HEALTHY AND
DISEASE STATES.
ALSO TO LEVERAGE EXPLORATORY
STUDIES TO DEVELOP GENERALIZABLE
DATA HARMONIZATION, INTEGRATION
AND ANALYSIS METHODS, BEST
PRACTICES AND STANDARDS, AND
FINALLY TO CREATE A
MULTIDIMENSIONAL DATASET AND
VISUALIZATION PORTAL THAT IS
AVAILABLE TO THE WIDER RESEARCH
COMMUNITY.
AND IS INTEROPERABLE WITH DATA
FROM OTHER CONSORTIA AND
INITIATIVES.
SO THIS IS AN OVERALL
ORGANIZATIONAL STRUCTURE OF
MOHD.
IT IS A CONSORTIUM, IT HAS
MULTIPLE SITES AS YOU CAN SEE.
IT IS ACTUALLY VERY LEAN IN
BUDGET AND VERY AMBITIOUS, AS
WE'RE ALL USED TO FOR A LOT OF
THESE TYPES OF STUDIES.
SO THERE'S AN OPERATIONAL
COMMITTEE AND A STEERING
COMMITTEE, THE STEERING
COMMITTEE IS CONSTRUCTED
BASICALLY BY NIH PROGRAM, STAFF
AND THE PIs OF THE DIFFERENT
DISEASE STUDY SITES.
SO -- AND THE DATA COORDINATING
CENTER AND THE OMICS PRODUCTION
CENTER.
SO DISEASE STUDY SITES ARE
LISTED HERE.
THERE'S THE DATA ANALYSIS CENTER
AT UMASS LED BY WENG AND AN
OMICS PRODUCTION CENTER LED BY
GARY PATTI AT WASH U.
AND WE ALL WORK TOGETHER TO
DEVELOP HARMONIZED MEASUREMENTS,
WHICH INCLUDE THINGS LIKE
CDEs, BIOSAMPLES, WE ALSO
DECIDE JOINTLY ON BIOSPECIMENS
AND ASSAYS.
SO THIS IS JUST A SCHEMATIC OF
WHAT WE CALL MOM HEALTH OR THE
MULTI-OMICS FOR MATERNAL HEALTH.
IT IS FOCUSED VERY MUCH ON
ACTUALLY POSTPARTUM HYPERTENSIVE
DISEASE.
SO WE ARE RECRUITING PEOPLE
EARLY IN PREGNANCY, COLLECTING
MULTIPLE TIME POINTS DURING
PREGNANCY, THROUGH DELIVERY, AND
THEN ONE-YEAR POSTPARTUM.
THERE IS A LOT OF EMPHASIS ON
THE DIVERSITY OF THE COHORT
THAT'S GOING TO BE COLLECTED, AS
WELL AS I MENTIONED HARMONIZED
MEASUREMENTS WHICH INCLUDE A LOT
OF EXPOSURE DATA.
THIS IS ACTUALLY GOING TO BE RUN
ACROSS FOR MOM HEALTH TWO SITES,
VANDERBILT AND UCSD AND FROM
THOSE SITES WE ANTICIPATE A
REALLY DIVERSE COHORT.
SO I'M GOING TO TALK ABOUT SOME
OF THE ISSUES ABOUT
HARMONIZATION ACROSS THE
DIFFERENT DSSs, DACC AND THE
OPC.
WE'RE GOING TO START TALKING
ABOUT MEASUREMENTS.
SO THESE ARE GOING TO BE VERY
EXTENSIVE AND I'M SURE ALL THE
GROUPS THAT HAVE DONE BIOBANKING
AND OTHER SORTS OF ANALYSES
APPRECIATE THERE'S THIS BALANCE
BETWEEN BEING COMPREHENSIVE AND
BEING OVERWHELMING WITH TOO MUCH
BURDEN ON THE PARTICIPANTS.
ONE INTERESTING THING WE'VE RUN
INTO IS THE WHOLE CONSORTIUM IS
PRIORITIZING A BREADTH OF DATA,
BUT ONE INTERESTING THING IS
THAT IT'S ACTUALLY SOMETIMES
KIND OF A TOUGH SELL TO ASK
SITES NOT COLLECTING -- THIS IS
ONE OF THE THINGS OUR GROUP HAS
BEEN ADVOCATING FOR IN THE
MEASUREMENTS WORKING GROUP.
IF YOU ACTUALLY LOOK AT
ALL-OF-US, IT HAS VERY LITTLE
PREGNANCY DATA.
IT'S ACTUALLY -- IF YOU DO A
SEARCH OF THE AVAILABLE FIELDS
INCLUDING THE BILLING FIELDS, IT
SAYS THAT 8% OF WOMEN 40 AND
OVER HAVE EVER BEEN PREGNANT.
AND WE KNOW THAT'S NOT TRUE.
AND IT REALLY LIMITS THE STUDY
OF THE EFFECT OF PREGNANCY ON
THE GENOME LATER IN PREGNANCY IN
THAT LARGE COHORT.
SO THIS IS WHAT WE'RE STRIVING
TO NOT RUN INTO WITH THIS
PARTICULAR CONSORTIUM.
IN TERMS OF BIOSPECIMENS, THE
APPROACH THAT IS BEING DONE NOW
IS TO HAVE A SET OF CORE
BIOSPECIMENS THAT EVERY DISEASE
STUDY SITE COLLECTS INCLUDING
THOSE BEING ANALYZED UNDER THE
CURRENT BUDGET AS WELL AS
LOOKING FORWARD TO ASSAYS THAT
ARE HIGH PRIORITY IF FUNDING
BECOMES AVAILABLE AS WELL AS,
QUOTE-UNQUOTE, FUTURE-PROOFING
FOR NEW TECHNOLOGIES THAT WE MAY
NOT EVEN HAVE IN OUR MINDS YET.
SO LISTED HERE ARE THE STANDARD
PERIPHERAL BLOOD-TYPE THINGS,
WHOLE BLOOD, PLASMA AND SURE UM,
WHITE BLOOD CELLS, THEN THERE
ARE SOME THAT ONE OR A SUBSET OF
DSSs WILL COLLECT DEPENDING ON
THE BIOLOGY OF THE DISEASE AND
THE FEASIBILITY OF THE SITES,
AND THIS INCLUDES TISSUE, LIKE
FOR US, PLACENTA, AND OTHER
BIOFLUIDS.
THE OTHER IMPORTANT THING IS WE
ALL AGREE IF WE'RE GOING TO
COLLECT A GIVEN TYPE ACROSS TWO
OR MORE STUDY SITES, THAT THE
SOPs WILL BE SHARED AND
HARMONIZED.
AND THEN IN TERMS OF ASSAYS,
THIS IS ALWAYS TRICKY, RIGHT,
BECAUSE MONEY IS ALWAYS LIMITED,
AND SO WE'VE WORKED A LOT ACROSS
THE DSSs, THE OPC AND THE DACC
TO DECIDE WHICH ASSAYS ARE GOING
TO BE DONE, TURNS OUT THAT EVEN
THOUGH ALL SITES WILL COLLECT
THREE TIME POINTS INITIALLY,
WE'RE PROBABLY ONLY GOING TO BE
ABLE TO COLLECT DATA ON THE
FIRST AND THE LAST TIME POINTS.
AND THEN HAVE TO MAKE SOME
DECISIONS ABOUT PRIORITIZATION
OF WHAT TO ANALYZE FOR THE
INTERVENING TIME POINT.
AND THEN IT'S BEEN FUN BUT ALSO
IT'S BEEN CHALLENGING TO TRY TO
COME UP WITH THE LIST OF THE
NEXT PRIORITY TYPES OF ASSAYS TO
DO IF FUNDING BECOMES AVAILABLE.
SO MOHD IS JUST STARTING.
WE BASICALLY JUST FINISHED OUR
FIRST YEAR BUT THAT WAS ABOUT
SEVEN MONTHS LONG SO WE'RE JUST
GETTING READY TO FINISH
HARMONIZATION, GET THE S.O.P.s
IN ORDER AT START ENROLLING FOR
THAT PROJECT.
SO I WANT TO TELL JUST A LITTLE
BIT ABOUT A PROJECT THAT HAS
BEEN COMPLETED IN TERMS OF WHAT
WE CALL DISCOVERY AND VALIDATION
OF BIOMARKERS, BUT HOPEFULLY
WILL BRING UP SOME SORT OF
THOUGHTS ABOUT THE UTILITY
POTENTIALLY OF SOME OF THE
RESOURCES THAT EXIST OR FUTURE
RESOURCES FOR VALIDATION.
SO I'M GOING TO TALK A LITTLE
ABOUT XRNAs AS EVIDENCE FOR
PRE-ECLAMPSIA SO OUR RATIONALE
IS -- I DON'T THINK I NEED TO
SELL TO THIS CROWD, BUT
HYPERTENSIVE DISORDERS OF
PREGNANCY ARE COMMON, CLINICALLY
IMPORTANT AND CAN BE DIFFICULT
TO DISTINGUISH FROM EACH OTHER.
AND THAT ACCURATE METHODS FOR
EARLY DIAGNOSIS AND PROGNOSIS
SUBSETTING OF HDP MAY REDUCE
UNNECESSARY HOSPITAL ADMISSIONS,
REDUCE UNNECESSARY EYE
ATROAGENIC PRETERM DELIVERIES,
SO WE DON'T MISS THE BOAT ON
BABIES THAT REALLY SHOULD BE
DELIVERED.
SO THIS IS A PRETTY SIMPLE STUDY
DESIGN.
WE COLLECTED SERUM SAMPLES,
PERFORMED SMALL RNA SEQUENCING,
DIVIDED THE COHORT INTO
DISCOVERY AND VERIFICATION WITH
MATCHED NUMBERS OF CASES AND
CONTROLS FOR BOTH THE DISCOVERY
AND VERIFICATION SUBCOHORTS, AND
THESE WERE WOMEN PRESENTING TO
TRIAGE FOR EVALUATION OF
POTENTIAL HYPERTENSIVE DISEASE
OF PREGNANCY, WHICH IS WHY WE
DIDN'T DO -- WE JUST TOOK
ALL-COMERS BUT YOU CAN SEE
THERE'S A HIGH RATE OF CASES
BECAUSE THESE WOMEN CAME IN FOR
EVALUATION OF POTENTIAL
PRE-ECLAMPSIA SO WE DID THE XRNA
ANALYSIS AND FOCUSED ON
MICRORNAs AND DID THE ANALYSIS
IN TWO WAYS, ONE LOOKING AT EUN
EYE VARIATE AND BIVARIATE
MICRORNAs PROVIDING
INTERNAL -- SO IN TERMS OF
UNIVARIATE CAN'T DATE MARKERS,
I'M SHOWING A HEAT MAP WITH A
NUMB NUMBER OF THESE.
KNOW ABOUT CHROMOSOME 19 BEING
AN IMPORTANT LOCUS FOR A CLUSTER
MICRORNAs, THAT SHOWED UP, AS
WELL AS A LOT OF PEOPLE KNOW
ABOUT THE LET-7s SHOWED UP AS
WELL.
TURNS OUT THE LET-7 AND
MICRORNAs THAT TRAVEL WITH IT
ARE ACTUALLY LOWER IN
PREECLAMPSIA CASES THAN NOT, AND
THE CHROMOSOME 1 19 ONEs IN
GENERAL ARE HIGHER.
THEN THESE ARE THE BIVARIATES.
INTERESTINGLY A LOT OF THINGS
SHOWED UP AT EUN VAIR YATS ALSO
SHOWED UP AS ONE OF THE PARTNERS
IN MANY OF THE BIVARIATES,
INCLUDING I'M CIRCLING HERE THE
CHROMOSOME 19 AND THE
LET-7 MICRORNAs.
ONE THING THAT YOU MIGHT SEE IS
THAT IN TERMS OF LUMPERS AND
SPLITTERS, I'M A SPLITTER AND
YOU CAN SEE FROM THE COLOR BARS
AT THE TOP LOOKING AT ALL THE
DIFFERENT METADATA ELEMENTS,
THESE ARE ALREADY VERY
SIMPLIFIED, IN TRYING TO FIND
PATTERNS BETWEEN WHAT WE SEE IN
TERMS OF THE PATTERNS OF THE
EXPRESSION VERSUS THE METADATA.
BECAUSE YOU CAN FIND INTERESTING
THINGS THAT YOU DON'T EVEN
EXPECT.
FOR EXAMPLE, WE FOUND IN A
DIFFERENT STUDY LOOKING AT PAIN,
THAT THERE'S A MICRORNA THAT
TRAVELS VERY MUCH WITH AFRICAN
AMERICAN ANCESTRY THAT WE NEVER
LOOKED AT OR WAS AWARE OF, AND
WE FOUND ONE PRIOR PAPER LOOKING
AT IT.
IT WAS ONLY BY LOOKING AT THESE
MILLIONS OF COLOR BARS THAT WE
SAW SOME ASSOCIATIONS BECAUSE WE
HADN'T EVEN THOUGHT TO ASK THAT
QUESTION.
SO WITH THESE KIND OF DATA CORE,
YOU CAN FIND BIOMARCS BUT YOU
CAN ALSO LOOK AT INTERESTING
PATTERNS ACROSS NOT JUST -- HERE
WE SPLIT OUT ACROSS ALL THESE
DIFFERENT CATEGORIES.
SEVERE PRE-ECLAMPSIA
SUPERIMPOSED, I KNOW THESE ARE
NOT CURRENT CLINICAL LABELS THAT
WE USE BUT THIS IS WHAT WE USE
AS A SHORTHAND IN RESEARCH AND
WE ACTUALLY HAVE VERY DEFINED
PATTERNS OF THE DIFFERENT
CRITERIA THAT PUT PEOPLE IN
THESE CATEGORIES.
OTHER, THESE ARE KOOKY CASES
THAT HAVE WEIRD LIKE CHRONIC
PROTEINURIA OR SOMETHING LIKE
THAT.
SEVERE HYPERTENSION, MILD
HYPERTENSION AND NORMAL.
YOU CAN SEE THERE'S INTERESTING
PATTERNS OF SOME OF THESE
BIOMARKERS, SOME THAT GO
ESSENTIALLY MONO TONGUELY FROM
SEVERE TO QUOTE NORMAL.
THE SECOND ONE IN B SHOWS THAT
ALL OF THE PREECLAMPSIA ONES ARE
HIGHER AND THEN ALL OF THE
NON-PREECLAMPSIA INCLUDES
CHRONIC HYPERTENSION ARE LOWER,
AND THEN ON THE BOTTOM, SOME
INTERESTING THINGS WHERE, FOR
EXAMPLE, MILD HYPERTENSION
ACTUALLY LOOKS A LITTLE BIT MORE
LIKE THE PREECLAMPTIC GROUP HERE
THAN THE SEVERE HYPERTENSION.
SUGGESTING THAT THERE'S
INTERESTING PATTERNS OF BIOLOGY
THAT BASICALLY TRAVEL WITH
DIFFERENT PHENOTYPES
DIFFERENTLY.
FROM THESE DATA, WE CAN ALSO
LOOK AT THE TISSUE SOURCES SO WE
DECONVOLUTED THE DATA WITH
SIGNATURES OF MICRORNAs FROM
DIFFERENT TISSUES, AND FOUND NOT
SURPRISINGLY THAT PLACENTA WAS A
BIG SOURCE OF RNA BIOMARKERS AS
WELL AS LIVER AND PLATELETS AND
RED BLOOD CELLS.
AND THEN OUR CONCEPT HERE WAS TO
TRY TO THINK LIKE A CLINICIAN,
SO LIKE A CLINICIAN THE WAY I
THINK ABOUT WHEN A PERSON COMES
IN IS I THINK OKAY, WHAT BIG CAT
DPRI OF DISEASE CATEGORY OF DISN
AND THEN SUBSEGHT SUBSETTING S.
WE TOOK THE VERY TOP ONE AND
THEN LOOKED TO SEE IF WE COULD
SUBSET DISEASE AND NOT DISEASE,
PREECLAMPSIA, NOT, AND YOU CAN
SEE THAT ON THE RIGHT, AND THIS
IS JUST FROM LOWER TO HIGHER OF
THIS BIOMARKER, THAT WE HAVE
ENITCHMENT OF DISEASE ON THE
RIGHT, THE BLUE, SO WE JUST SORT
OF CUT THOSE OUT, AND WE TOOK
THE REMAINING SAMPLES, DID XG
BOOST AGAIN TO THE TOP HIGH OR
THE BIOMARKER THERE, SORT IT
AGAIN, TOOK AGAIN THE DISEASE,
AND THEN DID IT A THIRD TIME AND
WHAT YOU SEE IS WITH THESE
THREE, YOU END UP WITH BEING
ABLE TO SEPARATE 90% OF YOUR
DISEASE IN YOUR ASSIGNED GROUP
AND 90% NORMAL OVERALL IN YOUR
QUOTE NORMAL GROUP, THERE'S A
LITTLE BIT OF BLEED-THROUGH BUT
ALSO INTERESTINGLY WHEN YOU LOOK
AT THE SECOND COLOR BAR, THE
MORE VEER CASES WERE THE ONES
-- THE MORE SEVERE CASESYOU GO.
THE NEXT TIME YOU GOT MORE
SUPERIMPOSED AND SOME MILD, AND
THEN THE LAST GROUP YOU STARTED
GETTING SOME SEVERE HYPERTENSION
IN YOUR QUOTE DISEASE GROUP.
SO THIS IS A WAY OF KIND OF
SUBSETTING YOUR DIFFERENT
SEVERITIES BY DOING SERIAL
ASSESSMENTS WITH SERIAL
BIOMARKERS.
THIS IS THE LAST SLIDE, I
BELIEVE.
SO WE THEN ADDED IN PROTEOMIC
BIOMARKERS.
EVERYBODY KNOWS ABOUT SFLT/PLGF.
IF YOU DID SFLT/PLGF AT THE
STANDARD CUTOFF OF 38, SPEAS FIS
IT INTO THE TOO BAD.
AS WE ALL KNOW, FROM A LOT OF
THE NICE RECENT STUDIES, IF YOU
PUT THEM TOGETHER AND HERE'S
THIS SORT OF DECISION TREE THAT
I'VE USED HERE, WE ACTUALLY
CUSTOMIZE THE SFLT/PLGF RATIO
BASED ON WHICH ARM THAT WE ENDED
UP WITH, WITH THE MICRORNA
BIOMARKER, AND IN THE END, WE
ACTUALLY GOT SORT OF THE BEST OF
BOTH WORLDS, THE SENSITIVITY AND
SPECIFICITY THAT WAS AS -- AND
SPECIFICITY AS GOOD AS THE
SFLT/PLGF SO WE LIKE TO STUDY IN
A LARGER DATASET TO VALIDATE TO
SEE WHETHER THIS COULD
POTENTIALLY BE USEFUL IN THE
CLINIC.
I THINK THAT'S THE END.
NEXT SLIDE I THINK IS MY -- I
JUST TALKED ABOUT THE FUTURE
DIRECTION SO THAT'S FINE, WE CAN
SKIP THAT, AND THEN THE MICRORNA
AND SFLT WORK WE JUST PUBLISHED
NOT THAT LONG AGO.
I'D LIKE TO THANK THESE FOLKS
FOR PARTICIPATING IN THE STUDY.
PANEL AT THE END, RIGHT?
>> YES, PANEL AT THE END.
NEXT SPEAKER IS MAGED
CONSTANTINE.
>> HI, EVERYONE.
I'D LIKE TO THANK NICHD AND
ORGANIZERS FOR PUTTING ALL THIS
WORKSHOP TOGETHER AND INVITING
US TO PRESENT.
AND SO FAR IT'S BEEN AN
IMPRESSIVE -- I'VE LEARNED A
LOT.
SO ON BEHALF OF DR. MENON AND
OTHER COINVESTIGATORS, I'D LIKE
TO TALK ABOUT THE DEVELOPING
EXTRACELLULAR VESICLE BASED
TRANSLATIONAL -- TRP FOR
MONITORING THERAPEUTICS RESPONSE
DURING PREGNANCY STUDY, WHICH
WAS RECENTLY FUNDED AND FROM
NICHD.
THIS IS MY ADDITIONAL
DISCLOSURES AND GRANT SUPPORT
AND COLLABORATIONS.
THE ADDITIONAL DISCLOSURE IS
THAT I'M NOT A BASIC SCIENTIST
OR EXOSOME EXPERT, SO ANY
EXOSOME QUESTIONS, DR. MENON IS
SMILING OVER THERE.
BUT BEFORE WE START, JUST A
QUICK BACKGROUND.
EVERYBODY KNOWS THIS, BUT THIS
IS THE BACKGROUND FOR OUR
STUDIES, THAT PREGNANT AND
LACTATING INDIVIDUALS HAVE BEEN
EXCLUDED FROM THE VAST MAJORITY
OF THERAPEUTIC TRIALS AND
CLINICAL DRUG DEVELOPMENT TRIALS
FOR MULTIPLE REASONS, AND THIS
EXCLUSION HAS THROUGHOUT
MULTIPLE LEVELS, INCLUDING
REGULATORY AGENCY DUES TO
ETHICAL CONCERNS OF INCLUDING
PREGNANT WOMEN, LACK OF INTEREST
FROM PHARMACEUTICAL COMPANIES
DUE TO FEARS OF LITIGATION AND
SMALL MARKET SHARE AMONG OTHERS.
INVESTIGATORS DUE TO LOGISTICAL
CONCERNS ABOUT ENROLL ENROLL PRT
WOMEN IN STUDIES AS WELL AS A
LOT OF OPERATIONAL WERNS WITH
THAT, AND LASTLY AMONG OTHERS IS
THE LACK OF VALID AND INNOVATIVE
BIOMARKERS TO ASSESS THE
PLACENTAL RESPONSE TO
THERAPEUTICS, AS WELL AS INFORM
SAFETY AND EFFICACY, ESPECIALLY
IN REALTIME.
ON THE OTHER HAND,
PLACENTAL-MEDIATED ADVERSE
PREGNANCY OUT COME COLLECTIVELY
WHICH INCLUDES DISEASES SUCH AS
HYPERTENSIVE DISORDERS,
PREECLAMPSIA, GROWTH
RESTRICTION, PRETERM BIRTH,
FETAL DEMISE, GESTATIONAL
DIABETES AMONG OTHERS, HAVE BEEN
INCREASING IN FREQUENCY OVER THE
PAST DECADES DUE TO MULTIPLE
REASONS, INCLUDING INCREASING
FREQUENCY OF SEVERAL
COMORBIDITIES SUCH AS OBESITY,
DIABETES, HYPERTENSION, AND
CURRENTLY AFFECT ALMOST TWEB
FIVE T25 TO30% OF PREGNANCIES AD
FREQUENCIES OF COMORBIDITIES,
MATERNAL AND NEONATAL
MORBIDITIES AND MORTALITIES,
ECONOMIC BURDEN, ONE OF THE
DRIVERS OF RACIAL AND ETHNIC
DISPARITIES IN PREGNANT
INDIVIDUALS IN THE UNITED
STATES, AND DESPITE ALL OF THIS,
IT'S BEEN REALLY LIMITED
PREVENTIVE STRATEGIES TO REDUCE
THE BURDEN AND FREQUENCY OF
THESE CONDITIONS.
CURRENT RECENT UNDERSTANDING OF
EX-CELLULAR VESICLES OR EXOSOMES
NATURALLY OCCURRED IN
NANOPARTICLES OF SMALLER 30 TO
200-NANOMETER SIZE, BETTER
UNDERSTANDING OF THEIR
CHARACTERISTICS AND ADDITIONALLY
THE CHARACTERIZATION OF THEIR
CARGO HAS BEEN FOUND IN MULTIPLE
STUDIES TO BE -- SPECIFICALLY
PRETERM BIRTH AS WELL AS
PREECLAMPSIA, AND THAT'S THE
THOUGHT PROCESS OF WHETHER WE
CAN USE THESE EXOSOME AS NOVEL
BIOMARKERS TO ASSESS THE
PLACENTAL RESPONSE TO SOME OF
THERAPEUTICS, AND SAFETY.
AND THIS THROUGH THE SUPPORT OF
THE MPRINT OPPORTUNITY FUND,
SMALL PILOT FUNDS TO CONDUCT
PILOT STUDIES FOR PROOF OF
CONCEPT FOR OUR IDEA.
IN THIS STUDY, WE ENROLLED
PEOPLE WHO ARE AT RISK OF PLEA
ECLAMPSIA RECEIVING ASPIRIN,
WHETHER IT'S 81 OR 162 MG AS
PART OF CLINICAL CARE AND
CONTROL LOW RISK GROUP WHO DID
NOT RECEIVE ASPIRIN, AND SAMPLES
WERE COLLECTED FROM THIS GROUP
AROUND 28 WEEKS THROUGH LOCAL
SMALL BIOBANK, AND IN THIS
COHORT, RATE OF PREECLAMPSIA WAS
29% IN THE CONTROL GROUP VERSUS
18% IN THE ASPIRIN GROUP.
EXOSOMES WERE ISOLATED USING
MULTISTEP SENT FEW GAITION,
FOLLOWED BY ULTRA SENT FEW
GAITION, SIZE EXCLUSION COLUMN
PURIFICATION TO EXCLUDE OTHER
PROTEINS AND THEN ANALYZE.
WHAT WE FOUND IS THE OVERALL
SIZE AND SHAPE OF THESE EXOSOME
DID NOT DIFFER BETWEEN THOSE WHO
ARE EXPOSED TO ASPIRIN AND THE
CONTROL GROUP, IN ADDITION, THE
EV MARKERS WERE SIMILAR AMONG
THE EXOSOMES FROM THE DIFFERENT
GROUPS IN THE STUDY, WHICH LED
US TO FOCUS MORE ON THE CARGO
AND USING DATA DEPENDENT
ACQUISITION BASED MODEL MASS
SPECTROMETRY WHICH WAS DONE --
THE LAB AT OHIO STATE, USING --
WE WERE ABLE TO IDENTIFY A WHOLE
BUNCH OF PROTEINS THAT WERE
EXPRESSED WITHIN THESE EXOSOMES,
AROUND 432 PER EXOSOME, THE DATA
WAS RUN AND THEY WERE EA ABLE TO
GENERATE A HEAT MAP AND FROM
THIS USING 1% POST DISCOVERY WAS
HAPPENING.
CAN YOU GO BACKWARD, PLEASE?
SO FROM THE HEAT MAP USING 1% --
DISCOVERY RATE, WE WERE ABLE TO
IDENTIFY 14 PROTEINS THAT WERE
DIFFERENTIALLY EXPRESSED AMONG
GROUPS WHO WERE EXPOSED TO
ASPIRIN, AND THE HIGHEST GROUP,
AND THOSE WHO WERE NOT.
TO KIND OF SUPPORT THE
HYPOTHESIS OF THE UTILITY OF THE
CARGO FOR THESE EXOSOMES TO HELP
MONITOR THE RESPONSE TO
MEDICATIONS IN PREGNANCY.
AND THAT DROVE THE OVERALL
PROJECT, WHICH HAS AN OBJECTIVE
TO DEVELOP A NEW PLATFORM
THROUGH NICHD SUPPORT TO USE
EXOSOMES PROFILING AS NOVEL
BIOMARKERS TO MONITOR ADVERSE
PREGNANCY OUTCOME, RESPONSE TO
THERAPEUTICS.
FOR THIS AS A PROOF OF CONCEPT,
WE WANTED TO STUDY PREECLAMPSIA
AS THE HALLMARK OF THIS ADVERSE
PREGNANCY OUTCOME AS WELL AS
ASPIRIN AS A THERAPEUTIC AGENT
OF CHOICE TO SHOW THE UTILITY OF
THIS PLATFORM.
KNOWING THAT ASPIRIN IS THE --
MEDICATION RIGHT NOW TO PREVENT
PRE-ECLAMPSIA THE OVERALL THE
AIMS OF THE PROJECTS INCLUDE ONE
TO DEVELOP AND VALIDATE THE
MULTI-MARKER PANEL OF EV PROAT
YOWM PROFILE, BOTH IN MATERNAL
AND FETAL EVs, FOR MONITORING
OF PLACENTAL FUNCTION IN
RESPONSE TO ASPIRIN THERAPY AND
NUMBER TWO, TO DEMONSTRATE THAT
MATERNAL AND FETAL EV PROTEOME
PROFILE IN THE SECOND AND THIRD
TRIMESTER PREGNANCY DIFFER
BETWEEN PEOPLE WHO DEVELOP
PREECLAMPSIA AND CORRELATE WITH
ASPIRIN DOSE OR SLI SICK ACID
CONCENTRATIONS, IN ADDITION TO
DEMONSTRATE CHANGES, WHETHER
THEY CORRELATE WITH THOSE
COMMONLY USED IN PREGNANCY WITH
PREECLAMPSIA AS WELL AS OTHER
CLINICAL OUTCOMES SUCH AS
PRETERM BIRTH AND GROWTH
RESTRICTION.
FOR THIS WE HAVE PUT TOGETHER A
MULTIDISCIPLINARY TEAM INCLUDING
MATERNAL FETAL MEDICINE AND
HYPERTENSIVE DISEASE EXPERT,
MYSELF AND KARA ROOD,
PHARMACOLOGY TEAM, PROTEOMICS,
AND BIOMEDICAL INFORMATICS
EXOSOME BIOLOGY EXPERT LED BY
DR. MENON AS WELL AS OTHER
INVESTIGATORS INCLUDING OTHERS.
THE STUDY AS DESIGNED IS A
COHORT OF MORE THAN 1,000 PEOPLE
AT RISK OF HYPERTENSIVE
DISORDERS AND RECEIVING ASPIRIN
USED AS PART OF CLINICAL CARE OR
FOR SOME OF THESE PATIENTS WHO
ARE PARTICIPATING IN OTHER
CLINICAL TRIAL ASPIRIN IN
PREGNANCY AND THE GOAL IS TO
ULTIMATELY OBTAIN SAMPLES WHO
DID NOT DEVELOP PREECLAMPSIA IN
ORDER TO ADDRESS OUR AIMS.
THESE ARE THE SUMMARY OF THE
STUDY PROCEDURES.
AFTER ENROLLMENT IN THE STUDY,
PATIENTS WILL UNDERGO FOUR
BIOSPECIMEN COLLECTION VISITS
DURING PREGNANCY, INCLUDING
THREE DURING PREGNANCY AND ONE
AT TIME OF DELIVERY, AND DURING
THESE DIFFERENT BIOSPECIMEN --
BLOOD WILL BE COLLECTED FOR
ISOSOME ISOLATION FOCUSING
INITIALLY ON THE MATERNAL AS
WELL AS THE FETAL EXOSOMES, AND
ALSO LOOKING AT THE BIOMARKERS
AT BASELINE AND THEN FOLLOWING
THAT AFTER EXPOSURE TO ASPIRIN,
PATIENTS WOULD ALSO EDITIONALLY
COLLECT EXOSOMES AS WELL AS
BIOMARKERS AND USING SALICYLIC
ACID CONCENTRATIONS, AND THEN AT
TIME OF DELIVERY, CLINICAL
OUTCOMES AS WELL AS PLACENTAL
AND FETAL MEMBRANES IN THE REST
OF THE BIOMARKERS.
BIOMARKERS WILL BE ISOLATED
DURING THE ULTRA
CENTRIFUGATION -- THIS IS THE
ONE THAT WE'LL BE USING FOR NOW.
IN ADDITION TO -- AND THEN THE
PROTEOMIX WOULD BE USING
DATA-INDEPENDENT ACQUISITION
OPPOSITE OF WHAT WE'VE DONE IN
THE PILOT STUDY.
FOR THE PHARMACOKINETIC STUDY,
WE'LL HAVE MINIMUM PK SAMPLING
THROUGHOUT THE PREGNANCY IN
WHICH PATIENTS WILL UNDERGO
BLOOD COLLECTION TO MAKE THE KEY
POINTS DURING THE -- IN THE PK
CURVE OF EXPOSURE, WITH THE GOAL
TO CORRELATE THE EXPOSURE WITH
THE EXOSOME CARGO AND CLINICAL
OUTCOMES.
AND THE GOAL FROM THIS, THE
STUDY HAS BEEN -- TO OBTAIN
FUNDING AND THE STUDY HAS BEEN
REGISTERED AND WE GOT IRB
APPROVAL SO WE'RE READY TO START
IT.
ULTIMATE GOAL IS TO DEVELOP THE
PLATFORM TO SHARE IT WITH THE
SCIENTIFIC COMMUNITY AND THEN
HAVE IT ESPECIALLY WITH THE
MPRINT NETWORK.
IN ADDITION TO -- TO PRODUCE
EASIER ACCESSIBLE ACCESS TO THE
FINDINGS, FOR OTHER OUTSIDE
INVESTIGATORS TO TAP INTO IT AND
WORK WITH THESE DATA.
AND OBVIOUSLY PARTNERSHIP WITH
NICHD, MFMU NETWORK AS WELL AS
OTHER NETWORKS, NIH, INDUSTRY
AND OTHER OUTSIDE INVESTIGATORS,
ULTIMATELY -- I KNOW THERE ARE
TWO LARGE -- THREE LARGE
ACTUALLY ASPIRIN STUDIES THAT
ARE PLANNED ON GOING.
ONE IS -- ONE THAT WOULD BE
COMPARING TWO DIFFERENT DOSES OF
ASPIRIN AT 11 CENTERS IN THE
COUNTRY, PLANNING TO ENROLL
ALMOST 11,000 PATIENTS, AND
HOPEFULLY, YOU KNOW, AT THE END
OF IT, WE'LL BE ABLE TO LEVERAGE
THESE PLANNED STUDIES TO ENRICH
THE NETWORK AND ALSO SUPPORT
OTHER INVESTIGATORS PLANNING TO
CONDUCT SIMILAR STUDIES.
THANK YOU, AND HAPPY TO TAKE ANY
QUESTIONS AT THE END.
>> THE NEXT SPEAKER IS HEATHER
BOWERMAN OF DOTLAB.
>> GREAT.
HELLO, EVERYONE, AND THANK YOU
FOR THE INVITATION TO BE A PART
OF THIS FANTASTIC DAY.
I AM REALLY EXCITED TO BE HERE
TO TALK A LITTLE BIT ABOUT WHAT
THIS LOOKS LIKE FOR US AS AN
EARLY STAGE STARTUP.
PARTICULARLY ONE IN A SPACE WITH
NO PREDICATE, AND HOW WHAT THESE
DISCUSSIONS REL REREA REALLY MES
ON A DAY-TO-DAY BASIS WHEN THESE
CONCEPTS ARE APPLIED AND REALLY
WHAT OUR JOURNEY HAS BEEN AS
WELL TO DEVELOP OUR OWN BIOROOSY
BIOREPOSITORY.
BEFORE I DIVE INTO THE SLIDES, I
WANT TO BE SURE TO GET TO A
COUPLE OF POINTS THAT HAVE STOOD
OUT TO ME FROM THE TALKS THIS
MORNING.
ONE WAS -- ONE JUST KIND OF AREA
THAT I KEEP COMING BACK TO IS
SOME FOLKS REFERRED TO THIS
NOTION OF PRECOMPETITIVE EARLIER
TODAY.
AND SO JUST KIND OF CHEWING ON
THAT TERM AND WHAT DOES THAT
MEAN FOR ME AS AN EARLY STAGE
PRIVATE COMPANY OR STARTUP, WHEN
I THINK ABOUT THE DEVELOPMENT OF
A NOVEL DIAGNOSTIC TEST, MAYBE
IT'S NOT THE SAME PATH ACROSS
ALL AREAS BUT LOOSELY SPEAKING,
IT'S DISCOVERY, SINK EL SITE SIE
VALIDATION, MULTICENTER
VALIDATION AND SOME SORT OF
PIVOTAL TRIAL.
DEFINING A POINT THAT COULD
POSSIBLY BE DEFINED AS
PRECOMPETITIVE WOULD BE NEARLY
IMPOSSIBLE BECAUSE THERE ARE
VARIOUS POINTS ACROSS THAT
JOURNEY WHERE A PRIVATE COMPANY
COULD CHOOSE TO COMMERCIALIZE
DEPENDING ON THE REGULATORY PATH
OF CHOICE.
SO I WAS KIND OF SPINNING ON
THAT AND IT REALLY DOESN'T MEAN
ANYTHING TO ME.
SO JUST WANTED TO SHARE THAT.
ANOTHER POINT IS THAT I THINK
THE STAKEHOLDERS THAT WE TRY TO
APPEASE AS AN EARLY STAGE STA
STARTUP, PARTICULARLY AS A
UNIVERSITY SPINOUT.
THE STAKEHOLDERS ARE JUST SO
VAST, AND SO WE'RE THINKING
ABOUT ALL THE TOPICS THAT HAVE
BEEN HIGHLIGHTED TODAY AS WELL
AS HOW THIS WILL MAXIMIZE OUR
FUTURE REIMBURSE WENT
OPPORTUNITIES, AS WELL AS HOW WE
CAN MAXIMIZE THE TERM NALG VALUE
OF OUR COMPANY BY GOING THROUGH
FDA, WE CAN DO LBTs BUT I
WON'T EVEN TOUCH THAT TOPIC
RIGHT NOW.
AND THEN I THINK THIRDLY, ONE
KIND OF NOMENCLATURE PIECE IN
DIAGNOSTICS THAT REALLY GETS
UNDER MY SKIN IS CONTINUING TO
TALK ABOUT WOMEN'S HEALTH AS A
MONOLITH.
SO I THINK YOU COULD HAVE THREE
DIFFERENT TALKS ON HOW IN OUR
CASE MICRO ATLA MICRORNAs FOR
ENDOMETRIOSIS, WHETHER YOU'RE
TALKING ABOUT THERAPEUTICS OR
MED TECH, DIAGNOSTICS, SO ACROSS
ALL THOSE TOPICS WOULD VARY
WIDELY.
SO I'M HERE TO SHARE MY
EXPERIENCE AND HOPEFULLY SERVE
AS A CASE STUDY, BUT I DON'T
THINK THAT I HAVE THE ANSWERS,
BUT I DO REALLY FEEL STRONGLY
THAT IF THERE'S ONE THING THAT
COULD BE DONE TO HELP THE
ADVANCEMENT OF THE
COMMERCIALIZATION OF THE AMAZING
INTELLECTUAL PROPERTY AND OUR
UNIVERSITIES, FEDERAL LABS AND
ELSEWHERE, IT WOULD BE TO
NATIONALIZE SOME SORT OF LIMB
SYSTEM.
BECAUSE I'VE HAD TO BUILD OUR
BIOREPOSITORY, ON WHICH THIS
TALK IS BASED, WE'VE BUILT THIS
FROM SCRATCH AND IT'S TAKEN
SEVEN YEARS.
AND NOBODY WANTS TO FUND THIS,
VENTURE CAPITAL IS THE WRONG
FINANCIAL INSTRUMENT FOR MOST
RESEARCH EX-ER ESPECIALLY IN A
SPACE WITH NO AT LEAST
NONINVASIVE PREDICATE ASIDE FROM
SURGERY, SO WE REALLY RELIED ON
GRANTS, WE'VE RELIED ON HIGH NET
WORTH INDIVIDUALS WHO ARE MORE
COMFORTABLE PARTICIPATING IN --
IT'S REALLY KIND OF VENTUREFUL
FLAN THPHILANTHROPY.
CORPORATE VENTURE, IT'S
TECHNICALLY VENTURE CAPITAL BUT
IT'S MUCH MORE PATIENT THAN
GOING AND KNOCKING ON A DOOR AND
SAYING -- ASKING FOR AN
INVESTMENT SAYING I'M GOING TO
HIT A CERTAIN MILESTONE ON A
TIME FRAME THAT WE AGREE TO,
WHICH IN A SPACE LIKE THIS,
WHERE THE DATASETS ARE NOT
AVAILABLE, PLEAK ALREADY ARE,
FORGET ABOUT CLINICAL, IT TAKES
TIME TO BUILD FROM THE GROUND
UP.
SO THERE'S SO MUCH WORK TO DO
AND I HOPE THAT WE CAN PINPOINT
SOME REALLY TACTICAL STEPS, AND
THE WHITE HOUSE DIALOGUE THAT'S
BEEN GENERATED RECENTLY IS A
HUGE STEP IN THE RIGHT
DIRECTION, BUT I THINK IT'S
REALLY IMPORTANT THAT WE DON'T
MISTAKE PROGRESS FOR SUCCESS.
SO SOME OF YOU MAY HAVE SEEN THE
ARPA-H ANNOUNCEMENT FOR
$100 MILLION, AND THAT'S
FANTASTIC, BUT I THINK WE'RE
STILL BARELY SCRATCHING THE
SURFACE TO REALLY MOVE THE FIELD
FORWARD.
SO I'LL GO INTO THE SLIDES ABOUT
WHAT WE DO AT MY COMPANY,
DOTLAB, IF YOU WANT TO MOVE TO
THE FIRST SLIDE.
SO AS BACKGROUND, WE'RE FOCUSED
ON A NONINVASIVE TEST FOR
ENDOMETRIOSIS.
I DON'T THINK THAT THE
DIAGNOSTIC NEED FOR DIAGNOSING
ENDOMETRIOSIS IS ONE SIZE FITS
ALL.
SO TODAY, THE AVERAGE DELAY TO
DIAGNOSIS IS 10 YEARS, WHICH I'M
SURE EVERYONE IN THE ROOM KNOWS,
HOWEVER F WE THINK ABOUT WHAT'S
NEEDED AND WHAT'S REIMBURSABLE
FROM A PRACTICAL PERSPECTIVE,
THE FIRST TIME A PROVIDER
INTERACTS WITH A PATIENT
PRESENTING WITH PELVIC PAIN OR
OTHER KEY SYMPTOMS OF THE
DISEASE, THE APPETITE TO
REIMBURSE AT THAT FIRST
INTERACTION VERSUS A PATIENT
WHO IS MAYBE CONSIDERING HER
SECOND IVF CYCLE, THOSE
DIAGNOSTIC OPPORTUNITIES ARE --
FROM A COMMERCIAL STAND POINT
ARE VASTLY DIFFERENT.
UNFORTUNATELY THE DIAGNOSTIC
DELAY IS EVEN WORSE THAN THE 10
YEARS THAT'S TYPICALLY CITED IN
WOMEN OF COLOR.
SO IT LOOKS LIKE THIS SLIDE IS A
LITTLE WARPED HERE, BUT POINT
BEING IS THAT THE DIAGNOSTIC
ODYSSEY IS LONG, AND ALL
STAKEHOLDERS THAT I MENTIONED
ARE IMPACTED BY THE DISEASE
PROGRESSION AND THERE HAVE BEEN
SO MANY EFFORTS OVER THE YEARS
TO LOOK AT VARIOUS MODALITIES
THAT MANY OF YOU ARE FAMILIAR
WITH, RANGING FROM IMAGING TO
PROTEINS TO MICRORNAs WHERE WE
HAPPEN TO FOCUS, BUT I THINK
WE'RE REALLY MAKING STRIDES WITH
OUR BIOREPOSITORY TO LAYER
MACHINE LEARNING ON TOP OF THE
BEST IN CLASS MARKERS THAT WE'VE
BEEN ABLE TO UNCOVER.
SO WHEN WE THINK ABOUT WHY THIS
PARTICULAR SPACE IS SO
CHALLENGING, IT'S REALLY BECAUSE
OF THE NONSPECIFIC NATURE OF
PELVIC PAIN, WHICH I WON'T GO
INTO WITH THIS GROUP, BUT
UNFORTUNATELY, IN THIS DISEASE
AREA, EVERYTHING ELSE NEEDS TO
BE RULED OUT BEFORE
ENDOMETRIOSIS WILL BE
MEANINGFULLY INVESTIGATED BY A
PROVIDER.
SO OUR GOAL WITH OUR WORK IS TO
ENSURE THAT WOMEN CAN RECEIVE
TREATMENT SOONER.
ONE THING THAT I'D LIKE TO
HIGHLIGHT IS THAT ONE OF THE
STAKEHOLDERS THAT WE INTERACT
WITH PRETTY OFTEN AND SHARE OUR
LATEST WORK WITH IS ON THE
PHARMA SIDE.
I THINK SOME OF YOU MAY BE
FAMILIAR WITH THE GNRH ANALOGS
THAT HAVE MADE IT PAST FDA IN
RECENT YEARS THAT'S REALLY THE
FIRST -- OR ALYSSA WAS THE FIRST
ENDOMETRIOSIS THERAPEUTIC TO
MAKE IT THROUGH FDA AFTER ABOUT
40 YEARS, BUT IT WASN'T
PRESCRIBED, AND THAT'S REALLY
DUE TO SURGERY REMAINING AS THE
GOLD STANDARD.
SO WHEN WE'VE BEEN DESIGNING OUR
TRIALS, THE STUDY DESIGN HAS
REMAINED THE SAME ACROSS ALL OF
OUR WORK WHERE WE COLLECT BLOOD
AND SALIVA SAMPLES AT THE TIME
OF LAB ROSS PEE ROS LAPAROSCOPYT
HISTOPATHOLOGY, WE REDRAW AT ONE
AND TWO-YEAR FOLLOW-UP VISITS
AND COLLECT CLINICAL DATA AT ALL
OF THOSE VISITS AS WELL.
AND SO ALL OF THOSE MOLECULAR
AND CLINICAL DATA POINTS HAVE
ALLOWED US TO PUT TOGETHER WHAT
WE BELIEVE IS A GLOBALLY UNIQUE
BIOREPOSITORY TO START TO DIG
INTO SOME OF THE TYPES OF
QUESTIONS THAT HAVE PERSISTED IN
THIS SPACE FOR SO LONG SUCH AS
THE RELATIONSHIP BETWEEN
ENDOMETRIOSIS AND OTHER
DISEASES.
SO OUR PIVOTAL TRIAL IS CALLED
EMPOWER, AND AS I MENTIONED,
IT'S FOE FOCUSED ON PROVIDING E
TRAINING AND VALIDATION TATA TO
SUDATA TOSUPPORT THE MACHINE LEG
MODELS AS WELL AS THE OTHER
BUSINESS MODELS TO HELP US
COMMERCIALIZE THIS TEST.
SO IF WE HAD CHOSEN TO
COMMERCIALIZE OUR WORK AT THE
SINGLE SITE VALIDATION STAGE,
FOR EXAMPLE, WE WOULD NOT HAVE
BEEN ABLE TO ACHIEVE OUR GOALS
OF GETTING KEY OPINION LEADER
BUY-IN, WHICH FOR US IS
ABSOLUTELY ESSENTIAL, AS WELL AS
PURSUING REIMBURSEMENT.
BUT THE JOURNEY IS NOT OVER
AFTER THE PIVOTAL TRIAL
ACTUALLY, SO WE STILL NEED TO
PUT TOGETHER A NOVEL CLINICAL
UTILITY DATASET, WHICH MEANS A
TOTALLY DIFFERENT SET OF
PROVIDER TYPES WHO ARE NOT
SPECIALISTS IN ENDOMETRIOSIS,
USE OUR TEST, AND THEN
DEMONSTRATE IMPROVEMENTS IN
OUTCOMES USUALLY MEASURED IN
PELVIC PAIN AFTER SIX TO 12
MONTHS.
THIS IS A BIG PART OF WHY THE
TIME HORIZON FOR GETTING OUT A
NOVEL DIAGNOSTIC TEST IS A
DECADE OR SO I THINK WHEN IT
COMES TO THIS BIOREPOSITORY
SPEES SPECBIO REPOSITORYSPEES SO
COMMENT ON THAT, I WOULD SAY MY
PATH TO CONCLUDING THAT WE
NEEDED TO BUILD OUR OWN
BIOREPOSITORY FROM THE GROUND UP
REALLY SORT OF SOLIDIFIED AFTER
TALKING TO ALL OF THE KEY
OPINION LEADERS IN THE SPACE,
TRYING TO LEARN FROM THEM WHAT
MIGHT BE AVAILABLE, MOST OF WHAT
WE -- OR I LEARNED ABOUT WAS FOR
ACADEMIC USE ONLY, OR WAS NOT
SUFFICIENTLILY WELL
CHARACTERIZED FOR US TO LOOK AT
THE MARKER TYPES OF INTEREST FOR
US, AND USUALLY DID NOT HAVE
CLINICAL DATA TO GO ALONG WITH
IT.
SO SOMEONE MENTIONED EARLIER
SHARING EXCEL FILES, DON'T DO
THAT WITH A BIG RED X THROUGH
IT, I THINK THAT'S SORT OF THE
BEST OF WHAT WE SAW OUT THERE
THAT WAS AVAILABLE, SO TO PUT
SOMETHING TOGETHER ON THE LEVEL
THAT WOULD ALLOW US TO SHARE OUR
WORK WITH FDA, LET ALONE THE
OTHER STAKEHOLDERS, IT REALLY
HAS BEEN NOT POSSIBLE TO DO
ANYTHING BESIDES BUILD IT
OURSELVES FROM THE GROUND UP IN
TERMS OF THE BIOREPOSITORY.
I GUESS ONE OTHER THING BEFORE I
MOVE ON TO THE NEXT SLIDE IS
THAT I THINK I'VE REALLY
OBSERVED AND THESE ARE SOME OF
OUR PARTNERS BUT WE CAN PASS
THIS, I REALLY OBSERVE THAT
INFORMATION MANAGEMENT SYSTEMS,
WHICH SOMEONE ELSE PRESENTED ON,
THAT THAT COMES INTO THE PICTURE
WAY TOO LATE.
SO TODAY, WE TALK ABOUT LIMBS IN
THE PRIVATE SECTOR, MOSTLY WHEN
WE'RE TALKING ABOUT HOW TO
DELIVER A COMMERCIAL TI TEST TON
ORDERING PROVIDER BUT WHY IS
THIS NOT UNIVERSALLY ADOPTED AT
THE R & D STAGE, IN SUCH A WAY
THAT SOMEBODY LIKE ME DOESN'T
HAVE TO GO ON A YEAR'S LONG
MISSION TO FIGURE OUT WHAT'S
AVAILABLE ULTIMATELY TO CONCLUDE
THAT THERE'S NOTHING AVAILABLE,
WHY CAN'T WE HAVE SOME SORT OF
STANDARDIZATION AROUND HOW
SPECIMENS ARE LABELED?
AND HAVE THAT REGULATED IN SOME
WAY BY A GOVERNING BODY WHERE WE
CAN HAVE SOME FAITH IN WHAT'S
REPORTED?
I THINK I COVERED MOST OF THIS
ALREADY BUT IN OUR EMPOWER
TRIAL, WE WORKED TO DESIGN THE
STUDY SO IT WAS BOTH POSSIBLE TO
ENROLL BUT ALSO MEET OUR
COMMERCIAL GOAL.
SO THIS IS WHERE WE LANDED, BUT
IT'S ALL AVAILABLE ONLINE AND
I'M HAPPY TO CHAT WITH ANYONE
AFTERWARDS ABOUT THE SPECIFICS
HERE.
BUT I THINK THE MOST
DISAPPOINTED THING FOR ME
ACTUALLY HAS BEEN THAT WE WERE
NOT ABLE TO FOLD IN A CLINICAL
UTILITY EFFORT INTO OUR CLINICAL
TRIAL, SO EMPOWER RAN AT OVER
TWO DOZEN TOP ACADEMIC SITES
ACROSS THE COUNTRY, BUT IN MANY
WAYS OUR WORK IS JUST BEGINNING.
TO GIVE SOME SENSE, WE
SCREENED -- THIS IS NOT THE END
OF THE STUDY BUT TO GIVE YOU A
SORT OF -- SOMETHING
REPRESENTATIVE, WE ENDED UP
SCREENING OVER 10,000 PATIENTS
FOR OUR TRIAL AND ENROLLED A
SMALL FRACTION OF THEM.
BUT WE DEVELOPED OUR INCLUSION
AND EXCLUSION CRITERIA IN ORDER
TO REALLY TRY TO HAVE THE
HIGHEST INTEGRITY SPECIMENS
POSSIBLE.
OUR PRODUCT IS CALLED DOT D
ENDO, OUR COMPANY IS CALLED
DOTLAB BUT OUR GOAL IS TO HAVE A
NONINVASIVE DIAGNOSTIC TEST
AVAILABLE FOR ENDOMETRIOSIS.
WE'RE ALSO INTERESTED IN
MONITORING, MEANING STAGING,
ALTHOUGH THOSE NO WIDELY ACCE
ACCEPTED STAGING SYSTEM, LARGELY
BASED ON VISUALIZATION, BUT THIS
DISEASE AS EVERYONE KNOWS IS
SOMETHING THAT REMAINS AN ISSUE
FROM THE TIME OF DIAGNOSIS
TYPICALLY UNTIL MENOPAUSE.
I THINK IN TERMS OF THE FUTURE
FOR OUR PARTICULAR COMPANY BUT
ALSO I THINK WHERE THIS FIELD IS
GOING FOR OTHER STARTUPS, I
THINK SOMEONE MENTIONED THIS
EARLIER, BUT IT'S FIERCELY
COMPETITIVE OUT THERE TO GET THE
RESORES ON THE BIOSTATISTICS
SIDE, SO ONCE WE HAVE THE WELL
CHARACTERIZED SPECIMENS, IT'S
ALMOST LIKE YOU -- IT'S
EVERY MAN FOR HIMSELF TO APPLY
THE NOVEL MACHINE LEARNING
MODALITIES IN ORDER TO REALLY DW
ANY CONCLUSIONS FROM THOSE
SAMPLES.
WHAT I HAVE ALWAYS REALLY FOUND
INTERESTING ABOUT OUR WORK IN
MICRORNAs IN PARTICULAR IS
THAT THERE'S BEEN ENORMOUS
OPPORTUNITY FOR US SORT OF
BECAUSE OF ALL THE FLAWS THAT
I'M HIGHLIGHTING AROUND THE LACK
OF STANDARDIZATION, BUT ALSO ON
THE PATENT SIDE THERE'S THIS
IDEA OF INVENTIVE SELECTION AND
THE CASE LAW WHICH MEANS THAT
WHEN IT'S NOT OBVIOUS WHICH
MICRORNAs OUT OF TENS OF
THOUSANDS THAT COULD BE
ASSOCIATED WITH A PARTICULAR
GENE TARGET IT'S NOT OBVIOUS
WHICH WILL BE ASSOCIATED WITH A
PARTICULAR DISEASE.
SO THAT HAS PRESENTED REALLY
UNIQUE OPPORTUNITIES ON THE IP
SIDE, BOTH IN TERMS OF PATENTS
BUT ALSO ON THE TRADE SECRET
SIDE.
SO OUR TRADE SECRETS OF OUR
COMPANY HAVE TO DO WITH NOT ONLY
HOW THE BIOREPOSITORY IS
ASSEMBLED, HOW WE HANDLE THE
SAMPLES, BUT ALSO THE ALGORITHM
ITSELF AND WHICH CLINICAL
FACTORS AND OTHER COMPONENTS
MAKE THEIR WAY INTO OUR
ALGORITHM, WHICH WILL NEVER BE
PUBLISHED.
SO IF WE THINK ABOUT PARTNERING
WITH A QUEST OR A LAB CORE, FOR
EXAMPLE, WE'RE REALLY FIRM IN
ALWAYS OWNING THE MACHINE
LEARNING PIECE.
THE LA GIST TICS PIECE, HANDLING
THE SAMPLES, WE'LL PARTNER WITH
ANYONE ON THAT BUT NOT ON THE
ALGORITHM SIDE.
SO THAT'S KIND OF BARELY
SCRATCHING THE SURFACE.
AGAIN, I THINK THAT WHAT I'M
SHARING IS REALLY JUST A SLICE
OF THE MED TECH SECTOR, BUT THIS
TALK WOULD BE COMPLETELY
DIFFERENT IF THIS WERE A
THERAPEUTICS COMPANY WHERE YOU
DON'T NEED SURGICALLY CONFIRMED
ENDOMETRIOSIS SAMPLES AND THOSE
BIOREPOSITORY NEEDS WOULD LOOK
NOTHING LIKE THIS.
SO I MEAN, I THINK WOMEN'S
HEALTH AND MATERNAL HEALTH IS
NOT A MONOLITH, BUT I'M REALLY
GLAD THAT THE LEADERSHIP HERE IS
DRIVING THE CONVERSATION.
SO THANK YOU SO MUCH.
>> OUR NEXT SPEAKER IS ROBIN
TUYTTEN.
>> HELLO.
FIRST OF ALL THANK YOU FOR
HAVING ME HERE.
I'M ALSO FROM A COMMERCIAL
COMPANY AND I WAS DELIGHTED TO
HEAR THE PREVIOUS SPEAKER.
I THINK MANY OF THE PAIN POINTS
WERE ADDRESSED HERE.
BUT I WILL BE TALKING HERE TODAY
IN MY CAPACITY AS A SCIENTIST.
SO THE TITLE, I DON'T THINK IT
FULLY AGREED WITH WHAT I MADE
THE PRESENTATION AFTERWARDS BUT
HERE WE GO.
SO I'LL VERY BRIEFLY TOUCH UPON
THE METABOLIC DIAGNOSTICS OF OUR
COMPANY, AND THEN HOW WE LOOK AT
PREECLAMPSIA AND PREECLAMPSIA
SCREENING AND HOW WE THINK THAT
BIOMARKERS CAN BE USED TO
IMPROVE THE UTILITY OF THE
SCREENING.
AND THEN WE NEEDED TO BUILD SOME
TOOLS TO ENABLE --
>> COULD YOU SPEAK DIRECT TO THE
MICROPHONE?
>> I'LL TRY TO, YES.
>> WE CANNOT HEAR CLEARLY.
>> MIGHT HAVE TO BEND DOWN A
BIT.
SORRY.
>> SORRY.
THANK YOU.
>> OKAY.
AND THEN I'LL TRY TO TALK A BIT
ABOUT WHERE WE'RE GOING, SO
WHERE WE REALLY TRY TO MAKE
TRANSLATIONAL RESEARCH
ACTIONABLE.
SO WHERE WE SEE OURSELVES AS A
COMPANY, SOMEWHERE AS A MIDDLE
MAN OR LIKE A CONDUIT, SO WE DO
NOT DISCOVER OUR OWN BIOMARKERS.
WE TAKE ON SO-CALLED BIOMARKERS
AND REALLY TRY TO SAY OKAY, ARE
THEY REAL, CAN WE VERIFY THEM IN
ANOTHER CONTEXT AND CAN WE THEN
SEE HOW WE CAN USE THEM TO
REALLY MAKE SENSE FROM A
CLINICAL UTILITY POINT OF VIEW,
SO CAN THEY HELP THE CLINICIAN,
CAN THEY IMPROVE THE HEALTH OF
THE MOTHER AND THE BABY, AND CAN
THEY ALSO MAKE SENSE FOR THE
HEALTHCARE SYSTEM.
IF WE CAN DO SO, IF WE CAN
DEFINE A SOLUTION WHICH
ADDRESSES THESE CLINICAL NEEDS
OR PRODUCT NEEDS, WE PACKAGE
THEM UP AND THEN DELIVER THEM TO
OTHER ACTORS SO WE DON'T SEE
OURSELVES AS MARKET-FACING.
WE REALLY TRY TO TAKE ON
BIOMARKERS, SEE ARE THEY REAL,
MAKE SENSE OF THEM THAT THEY CAN
REALLY HELP AND BECOME
ACTIONABLE, AND THEN BRING THEM
TO OTHER ACTORS WHICH HAVE A
MARKET FOOTPRINT.
SO WHEN THIS COMPANY WAS
ACTUALLY FOUNDED ON A PIECE OF
IP, SO THE COMPANY LICENSED A
SET OF PUTATIVE BIOMARKERS OR
METABOLOMICS BIOMARKERS SEEN TO
PREDICT PREECLAMPSIA IN EARLY
PREGNANCY, AND THAT WAS THE
STARTING POINT.
THE MISSION OF THE COMPANY AT
THAT STAGE WAS TO SAY OKAY, WE
WANT TO MAKE THIS A COMMERCIAL
VIABLE PROPOSITION, WHICH
ADDRESSES CLINICAL UTILITY.
SO MANY YEARS LATER, -- OUR OWN
TRANSLATIONAL RESEARCH JOURNEY,
WHICH REQUIRED US TO DEVELOP OUR
OWN ANALYTICAL TECHNOLOGIES TO
MEASURE BIOMARKERS.
WE DEVELOPED OUR OWN SUITE OF
MACHINE LEARNING TECHNIQUES TO
REALLY ADDRESS THIS QUESTION AND
WE ALSO ESTABLISHED -- OR WE
TOOK SOME PROCESS DECISIONS TO
ENABLE US TO WORK WITH BIOBANKS
BECAUSE WE ALSO NEED SAMPLES TO
DO THIS.
SO I CAN TALK A BIT MORE ABOUT
OUR WORK IN PRETERM
PREECLAMPSIA, AND ALSO WHAT ARE
THESE DECISIONS THAT ALLOWED US
TO GET ACCESS TO SAMPLES OF
13,000 PREGNANCIES AND SAMPLES
WHICH WE HAVE ON SITE.
SO I'M NOT GOING TO TALK ABOUT
PREECLAMPSIA, IT WAS ALREADY
TOUCHED UPON, BUT SOME IDEAS
ABOUT HOW WE ARE APPROACHING THE
PROBLEM.
SO AT THE TIME WHEN WE GOT
STARTED, PROFESSOR ROBERTS FROM
THE WOMEN'S RESEARCH INSTITUTE
IN PIT BURG, ONE OF THE KEY
LEADERS IN PREECLAMPSIA, WROTE
THIS VERY INTRIGUING AND MAYBE
THOUGHT-PROVOKING PAPER AT THE
TIME SAYING OKAY, IF WE KNOW SO
MUCH ABOUT PREECLAMPSIA, WHY
HAVEN'T WE CURED THE DISEASE?
AND THIS CAME ALL BACK TO THE
IDEA THAT, OKAY, THERE IS SO
MANY BIOMARKER DISCOVERY GOING
ON LEADING TO NEW BIOMARKERS BUT
THEY ALWAYS FAILED TO DELIVER --
ANOTHER CONTEXT, WHAT I'M
POSITING TO SAY, IT'S NOT THAT
THIS IS BAD RESEARCH, ACTUALLY,
NO, THE RESULT OF THE BIOMARKERS
DISCOVERY IS CONTEXT-DEPENDENT.
SO WHEN YOU FIND A BIOMARKER IN
A CERTAIN CLINICAL CENTER OR
DEMOGRAPHIC, THIS MIGHT WORK,
THIS MIGHT BE A BIOMARKER
APPLICABLE FOR THAT SPECIFIC
PATIENT DEMOGRAPHIC.
BECAUSE IT MIGHT SHARE MAYBE AN
UNDERLYING RISK PROFILE.
AT THE SAME TIME, IT ALSO -- THE
UNDERSTANDING THAT PREECLAMPSIA
IS NOT A SINGLE DISEASE, BUT
RATHER A SYNDROME OF --
COMPRISED OF MANY SUBTYPES OF
DISEASE.
SO THERE AGAIN, MAYBE,
PREECLAMPSIA IS
CONTEXT-DEPENDENT AND CERTAIN
RISK PROFILES WILL GENERATE
MAYBE CERTAIN EXPRESSION OF
CERTAIN SUBTYPES.
SO IF YOU THINK THAT THROUGH,
MAKING A TEST SCREENING FOR
PREECLAMPSIA, FINDING WOMEN AT
RISK OF PREECLAMPSIA, THAT WORK
OVERALL BECOMES VERY HARD, YES.
NEXT SLIDE.
BUT WE TOOK THAT ON BOARD, THIS
CONCEPT OF PROFESSOR ROBERTS IN
OUR OWN STRATEGY, SO OKAY, SO IF
WE NEED TO BE ABLE TO HEDGE
AGAINST THE PROBLEM THAT
SCREENING NEEDS TO BE
CONTEXT-SPECIFIC, BEING ABLE TO
DEAL WITH THAT, WE NEED TO FIND
MAYBE WAYS TO ADDRESS THIS
CHANGE IN RISK PROFILES ACROSS
DIFFERENT PATIENT DEMOGRAPHICS,
SO OF COURSE PATIENT DEMOGRAPHIC
IS VERY HARD TO SAMPLE, BUT THE
EPIDEMIOLOGY GIVES US SOME CUES
TO MAYBE SAY OKAY, CAN WE USE
EPIDEMIOLOGICAL DATA TO CREATE A
CERTAIN TYPE OF MATERNAL
PHENOTYPE WHICH MIGHT IN ITSELF
BE A PROXY FOR ENRICHED --
UNDERLYING SUBTEASE ORIS BEING
PROFILE FOR DISEASE.
AND -- FOR EXAMPLE, YOUR BMI, OR
I SARCOMAS I, MATHERE'S AN ASSON
BMI AND PREECLAMPSIA RISK, SO
LEAN WOMEN HAVE A LOWER RISK
TYPICALLY THAN OBESE WOMEN.
MAYBE YOU CAN FIT BIOMARKERS
THAT WORK SPECIFICALLY TO LEAN
WOMEN AND OBESE WOMEN.
THE SAME IS TRUE FOR RACE OR
ETHNICITY AND RACE, SO IT IS
WELL-KNOWN THAT WOMEN OF AFRICAN
ANCESTRY HAVE A HIGHER RISK FOR
PREECLAMPSIA THAN OTHER WOMEN.
MAYBE THERE IS BIOMARKERS THAT
FIT THIS RISK PROFILE BETTER.
SO WE TOOK THAT AS A WORKING
HYPOTHESIS.
WE DID -- WITH THE IDEA THAT OUR
SEARCH COULD BE HEDGING AGAINST
THESE CHANGES IN RISK PROFILES
IN TERMS OF DEMOGRAPHICS.
SO AS THE NAME OF THE COMPANY
SUGGESTS, WE'RE USING
METABOLITES D TO DO THIS, THEY'E
IN A WAY VERY GOOD IF YOU WANT
TO GET A SENSE OF WHERE YOU ARE
AT A CERTAIN STATE OF SAMPLING,
SO THE METABALOME IS REFLECTING
WHAT IS CODED IN THE GENOME BUT
IT IS ALSO REA SPONDING, SAY,
WHO YOU ARE, WHAT YOU EAT, YOUR
MICROBIOME, YOUR ENVIRONMENT,
THE EXPOSOME, AND YOU CAN
MEASURE THAT.
SO THAT'S THE IDEA OF
METABOLOMICS.
YOU REALLY MEASURE ALL -- YOU DO
A COMPREHENSIVE ANALYSIS OF THE
METABALOME.
THE PROBLEM IS, OF COURSE, THE
METABALOME HAS SUCH -- YOU
CANNOT BRING FORWARD TO THE
PATIENTS, SO THESE METABOLOMICS
STUDIES TYPICALLY DO FAIL TO
DELIVER ACTIONABLE -- SO YOU
HAVE TO REFORMULATE THE
QUESTION, CAN WE REALLY EXTRACT
METABOLITES OF INTEREST WHICH
STILL CARRY SOME INFORMATION,
BRING THEM TOGETHER TO MAKE A
TEST?
SO THAT'S WHAT WE'RE TRYING TO
DO.
SO VERY BRIEFLY ON SOME OF THE
TECHNOLOGIES AND THE TOOLS WE
DEVELOPED TO DELIVER ON WHAT WE
WANTED TO DO WAS SAY ESSENTIALLY
TAKING ON LOTS OF BIOMARKERS,
IDENTIFIED BY OTHERS, AND SEE
HOW THEY REALLY WORK AND CAN WE
FIT THEM WITH MAYBE CERTAIN RISK
PROFILES AND SEE IF YOU CAN USE
THAT INFORMATION TO IMPROVE
PREECLAMPSIA PREDICTION OR
PREDICTION OF ANY OF THE ADVERSE
PREGNANCY OUTCOMES.
SO WE NEED TWO CRITICAL
COMPONENTS.
SO FIRST WE NEED SOME TYPE OF
TRANSLATIONAL RESEARCH, A
PLATFORM WHICH WE CALL M-SCOUT,
ESSENTIALLY A LIBRARY -- WE'RE
ABLE TO SCREEN AND VERIFY ANY OF
THESE PUTATIVE BIOMARKERS IN AN
EFFECTIVE WAY, IN A CONTROLLED
WAY, AGAINST SAMPLES.
SO WE NEED A LIBRARY OF ASSAYS.
OF COURSE IF YOU WANT TO LOOK
FOR, VERIFY BIOMARKERS, AND TAKE
INTO ACCOUNT PHENOTYPE WE ALSO
NEED ACCESS TO SEVERAL, SEVERAL
SAMPLES.
SO AT THE END OF PREGNANCY --
EARLY PREGNANCY IN THE FIRST
TRIMESTER, WE WANT TO TAP INTO
THE ASPIRIN -- THAT YOU CAN
PREVENT SOME OF THE PREECLAMPSIA
HAPPENED, AND NEEDS TO BE WELL
ANNOTATED IN TERMS OF CLINICAL
INFORMATION AS WELL AS PREGNANCY
OUTCOMES.
SO WE DID THAT FIRST, WE BUILT
M-SCOUT, AND WE SEE IT AS A
GENERATOR OF WELL CONTROLLED
METABOLITE BIOMARKER DATA, WE
LOOK AT MANY, MANY METABOLITE
BIOMARKERS AT THE SAME TIME.
IN A TARGETED WAY WE ALWAYS KNOW
WHAT WE ARE MEASURING, SO
WE'RE -- MAKE AN ASSAY TO PUT
THAT STANDARD SO WE KNOW WHAT
WE'RE MEASURING.
IT'S AN OPEN PLATFORM.
WE CAN ADD NEW BIOMARKERS OR
BIOMARKER CANDIDATES OVER TIE.
IT ALLOWS US TO QUANTIFY OR SEMI
QUANTIFY SO WE CAN LOOK FOR
DIFFERENCES BETWEEN GROUPS.
IT IS QUITE COST-EFFICIENT, AND
WE'VE BUILT A WHOLE SUITE OF
DATA ANALYSIS TOOLS AROUND TO
ANALYZE THE DATA.
WHEN WE BUILT M-SCOUT WE
DELIVERED THE DECISION THAT WE
ALWAYS WANTED TO START FROM A
SMALL AMOUNT OF SAMPLE.
AND WHY WAS THAT?
BECAUSE WE WANTED TO BE ABLE TO
ENGAGE WITH BIOBANKS BECAUSE WE
NEED SAMPLES AS WELL TO PROGRESS
OUR WORK.
SO WE FORCE OURSELVES TO ALWAYS
SAY WE WILL MEASURE EVERYTHING
WE WANT TO MEASURE IN 40 MICRO
LITERS OF SERUM OR 80 -- OF
PLASMA.
THEN IT ALLOWS US TO ENGAGE WITH
BIOBANKS AND SAY WE NEED ONLY A
SMALL AMOUNT OF YOUR PRESSURES
AND FINITE RESEARCH SOURCE TO DO
OUR WORK.
SO WHAT TYPICALLY HAPPENS IS WE
GET 50 TO 500 MICRO LITERS OF A
SAMPLE, AND WHAT WE THEN DO WHEN
WE ACCEPT THE SAMPLE IS WE
IMPLEMENT ONE FREEZE-THAW CYCLE
WHERE WE MANUALLY TRANSFER THE
SAMPLES TO ANOTHER SET OF FILES,
WHICH ARE INDIVIDUAL SMALL
VIALS, ALL INDIVIDUALLY BARCO
BARCODED, AND WE USE THAT
SAME MASTER PLATE TO MAKE A LOT
OF CLONES FOR THE MICRO LITER.
OURS IS ACTUALLY TO GO BACK TO
THIS RESOURCE WHEN WE NEED TO,
TO USE SAMPLES FOR REPLICATES IF
SOMETHING GOES WRONG IN THE
NEXT -- WE CAN GO BACK TO IT.
SO WE RESPOND MORE SAMPLES SO
THAT WE ARE ABLE TO USE THE
RESOURCE MAXIMALLY.
THE NICE THING ABOUT THESE
SAMPLE TYPES OR SAMPLE VIALS IS
YOU SEE THEY ALL ARE INDIVIDUAL.
SO IF YOU WANT TO APPLY STUDY
DESIGN, SO YOU WANT TO RANDOMIZE
THE SAMPLES, YOU CAN DO THAT IN
PLATE.
YOU CAN PICK YOUR SAMPLES AND
YOU ORGANIZE THEM IN PLATES.
AND THE NICE THING IS BECAUSE
THEY ARE ALL INDIVIDUALLY
BARCODED AND QR TOTAL, WE HAVE
THESE FLOOD BITS DUE TO
FACILITATE THAT.
AND MAYBE SAMPLE STORAGE HAS
BEEN DISCUSSED OFTEN HERE AS
BEING EXPENSIVE ON THE TAKING.
THESE FI.THESE VIALS ARE VERY EE
IN TERMS OF STORAGE SPACE.
YOU CAN FIT 24,000 VIALS IN ONE
FREEZER.
SO WE BUILT TOOLS.
WE HAVE METABOLIZED -- ADD US
USING -- OF COLLABORATIONS AND
ALSO THIS APPEAL WITH LOTS OF
DATA FOR SMALL VOLUME SAMPLE.
WE WERE ABLE TO ESTABLISH
COLLABORATION WITH BIOBANKS SO
WE HAVE EVERYTHING IN PLACE TO
ACTUALLY START DELIVERING ON
THIS.
AND EXECUTING ON OUR PLAN AND
OUR HYPOTHESIS.
SO AS ONE OF OUR EFFORTS WITH
THE FETAL MEDICINE FOUNDATION IN
LONDON, UK, WE RECEIVED 2,000
SAMPLES FROM 2,000 SINGLETON
PREGNANCIES TAKEN IN THE
FIRST -- AFTER FIRST PRENATAL
VISIT, LAST PAR, AS PART OF ROU,
WHERE THEY WILL ASSIST IN TERMS
OF BLOOD PRESSURES, DOPPLER,
WHICH IS RELEVANT TO
PREECLAMPSIA, CLINICAL AND
INFORMATION THAT WAS COLLECTED
AS WELL, SO ALL THAT INFORMATION
WAS THERE.
AND THE BLOTS WERE TAKEN FOR
BIOBANKING.
WE GOT SOME OF THE BLOTS TO DO
ANALYSIS AND WE ANALYZED THESE
BLOT SAMPLES WITH 50 METABOL
METABOLITES, TO ASSOCIATE WITH
PREECLAMPSIA RISK OR ANOTHER
COMPLICATION OF PREGNANCY.
ON TOP OF THAT, WE GOT
INFORMATION ON PROTEIN
BIOMARKERS PLUS -- SO WE -- 1635
UNCOMPLICATED PREGNANCIES, AND
866 COMPLICATED ONES OF WHOM 106
PRETERM PREECLAMPSIA, MEANS WE
HAVE DATA ON GDM SO ALSO -- NEXT
SLIDE.
USING THIS DATASET WE DESCRIBED
COMPREHENSIVE, FIRST ABLE TO
DEMONSTRATE THAT INDEED, CERTAIN
MMETABOLITES DO FIT OR DO ALIGN
WITH PHENOTYPE AS DEFINED BY
SIMPLE CHARACTERISTICS LIKE BMI.
THERE ARE CERTAIN METABOLITES
AND METABOLITE RATIOS WHICH ONLY
ACT AS A PREDICTOR OR BIOMARKER,
PREDICTOR FOR PREECLAMPSIA IN
LEAN WOMEN AND OTHERS -- IN
OBESE WOMEN, SO THIS CONCEPT
THAT INDEED THERE MIGHT BE
MATERNAL CHARACTERISTICS THAT
ALIGN WITH ON THE HIGH RISK
PROFILE IS PROVEN THERE.
THEN WE TOOK THAT HOME TO
ACTUALLY SAY OKAY, CAN WE USE
THESE BIOMARKERS AND ALSO HAVE
UTILITY TO BETTER CLASSIFY,
BETTER PREDICTION MODELS.
AND IT WAS THE NEXT PAPER WHICH
WE PUBLISHED LAST YEAR.
SO I'LL SPEAK ABOUT THAT JUST
NOW.
SO -- IN A WAY THAT WE SAY OKAY,
WHIWE ASSUME THAT THERE IS
DIFFERENT RISK PROFILES MAYBE
THAT ASSOCIATE WITH CERTAIN
OR -- CERTAIN -- SO WE -- IN
TERMS OF THIS CASE, BMI, AND FOR
EACH OF THESE SUBGROUPS, WE
CREATE A LOT USING MACHINE
LEARNING AND A LOT OF VERY
SIMPLE CLASSIFIERS.
TYPICALLY THE CLASSIFIER ONLY
HAS TWO TO FOUR PREDICTORS IN
THEIR -- OR VARIABLES IN
THEIR -- THEN IF WE MAKE THIS
COLLECTION OF ALL OF THESE
CLASSIFIERS, WE WILL ACTUALLY
SELECT THE TOP CLASSIFIERS FOR
PHENOTYPE, USING -- INTO AN
AVERAGE MODEL.
FOR EVERY WOMAN, FINDING THE
RISK IS ACTUALLY -- THE RISK
SCORE IS DEFINED BY TAKING THE
AVERAGE OF ALL THE CLASSIFIERS,
WHICH WILL -- FOR THAT WOMAN.
FOR EXAMPLE, IF YOU KNOW THAT
YOU'RE WHITE AND YOU'RE OBESE,
YOU WILL TAKE OUT THE MODELS
THAT ARE RELEVANT FOR WHITE AS
WELL AS OBESE -- FOR SOME
ETHNICITIES, WE DIDN'T HAVE
ENOUGH CASES SO PEEL FALL BACK
TO BMI CLASSIFICATION ONLY.
COMPARING IT WITH THE BEST
AVAILABLE AT THIS TIME IN TERMS
OF BIOMARKERS, SO -- ARTERIAL
PRESSURE AS A COMPARATOR, AND
THEN WE LOOKED -- IF WE ADME TAB
LIGHTS AS PART OF OUR SELECTION
OF METABOLITES -- WILL THEY
IMPROVE THE DETECTION FOR
PRETERM PREECLAMPSIA AND 10%
FALSE POSITIVE RATE EARLY IN
PREGNANCY.
OVER THIS COMPARATOR.
AND YOU CAN SEE THAT WE DO
IMPROVE THE DETECTION RATE WHEN
USING METABOLITES CONSISTENTLY,
EXCEPT IN THE OVERWEIGHT.
AND THIS MIGHT BE DUAL TO THE
FACT THAT ACTUALLY WE USE A VERY
CRUDE PHENOTYPING, BMI
CLASSIFICATION, AS A WAY TO --
ENRICH TO MAYBE AN UNDERLYING
PROFILE.
-- YOU HAVE OVERWEIGHT -- A
LEAN PROFILE, OBESE PROFILE
COMING TOGETHER AND THE SYSTEM
COLLAPSES.
BUT YOU CAN SEE THAT ACTUALLY IN
IS A WAY TO REALLY PERSONALIZE
RISK PREDICTION BY ADDING OR
MATCHING THE RIGHT METABOLITES
TO RIGHT AND MATERNAL PHENOTYPE.
SO NOW I'M GOING TO QUICKLY TAKE
A DETOUR ON WHAT ELSE -- HOW WE
CAN USE THIS GOING FORWARD.
SO IN THE U.S., THE CURRENT
PRACTICE FOR PREECLAMPSIA IS
JUST LIKE IN THE -- A CHECKLIST,
RISK FACTORS, AND IT WILL TELL
YOU IF YOU HAVE MORE THAN ONE OR
MO HIGH RISK FACTORS, THE
CLINICIAN IS RECOMMENDED TO GIVE
ASPIRIN.
THE SAME IS TRUE IF YOU HAVE
MORE THAN TWO -- TWO OR MORE
MOTHERS' RISK FACTORS.
THEN THERE IS ALSO THE OTHER END
OF THE GUIDANCE, IF YOU HAVE A
SINGLE RISK FACTOR, MAYBE YOU
SHOULD CONSIDER ADVISING TO GIVE
ASPIRIN.
SO IF WE WOULD LOOK LIKE A FEW
YEARS AGO, WHEELER ET AL.
ACTUALLY DID A VERY NICE
EXERCISE IN THE EXPOSURE TO ALL
THE RISK FACTORS IN THE U.S.
PREGNANCY POPULATION, 2019, SO
THEY HAVE VERY GOOD ESTIMATES,
WHAT THEY FOUND WAS IN ALL THE
PREGNANCIES, ALL THE WOMEN THAT
WOULD HAVE MORE THAN ONE HIGH
RISK FACTOR, IF YOU WOULD LOOK
AT THIS GROUP AS A
CLASSIFICATION, YOU WOULD HAVE A
SCREEN POSITIVE RATE OF 4.6%, SO
WOULD YOU IDENTIFY LESS THAN 5%
OF WOMEN AS BEING AT RISK TO
GIVE THEM ASPIRIN AND THIS IS
NOT CONTESTED.
HOWEVER, READING THAT GROUP, YOU
WOULD ONLY DETECT ABOUT 8.4% OF
THE WOMEN WOULD GET PREECLAMPSIA
OR GESTATIONAL HYPERTENSION, IN
THIS CASE.
ON THE OTHER SIDE, IF YOU WOULD
SAY -- IF YOU APPLY THE USPTF OR
ACOG GUIDELINES IN THE BROADER
SENSE, AND YOU WOULD SAY OKAY,
WE ONLY NEED ONE MORE HIGH RISK
FACTOR, YOU ARE VERY EFFECTIVE
IN FINDING WOMEN AT RISK, YOU
WOULD DETECT ABOUT 93% OF ALL
THE WOMEN.
HOWEVER, YOU'RE VURTLY SAYING VG
TO ALL WOMEN YOU'RE AT RISK, SO
THE SCREEN POSITIVE RATE IS 86%.
THE LATTER WOULD BE AGAINST ALL
GOOD SENSE, THE ADDED VALUE OF
SCREENING -- YOU WANT TO FIND
WOMEN AT RISK TO -- AND TO MAKE
SURE THERE WAS GOOD COMPLIANCE
WITH ASPIRIN.
JUST FOR THE SAKE OF THE
ARGUMENT, I WOULD LIKE YOU TO
REMEMBER THE -- OF 15%, IN THE
HIGH RISK GROUP AS DEFINED WITH
HAVING MORE THAN ONE HIGH RISK
FACTOR, YOU HAVE 15% RISK TO GET
PRE-ECLAMPSIA SO FOR EVERY 100
WOMEN THAT TEST POSITIVE FOR
THAT CRITERION, 15 OF THEM WILL
GET PREECLAMPSIA, YES?
THAT SEEMS TO BE WELL ACCEPTED
AS A NOURI -- GROUP TO GIVE WOMN
ASPIRIN.
SO PPV IS THAT NUMBER.
AS I SAID EARLIER, WE ASSESSED
THE IMPROVEMENT OUR METABOLITES
COULD GIVE OVER SAY THE BEST
AVAILABLE BIOMARKERS AT THIS
STAGE, AT DETECTION RATE FOR 10%
FALSE POSITIVE RATE WHICH IS A
TYPICAL CRITERIA WE SEE IN
PREECLAMPSIA SCREENING RESEARCH.
BUT THIS IS NOT REALLY GOOD
CRITERIA IN TERMS OF CLINICAL
UTILITY.
CLINICAL UTILITY IS BETTER
EXPRESSED IN POSITIVE PREDICTIVE
VALUES FOR EXAMPLE.
BUT POSITIVE PREDICTIVE VALUES
NEED YOU TO KNOW WHEN YOU WANT
TO KALG LAWT THEM, YOU NEED TO O
KNOW THE PRIOR RISK OR
PREVALENCE OF DISEASE BEFORE,
PRE-TEST, BEFORE YOU CAN
ACTUALLY PREDICT THIS IS MY
POSITIVE PREDICTIVE VALUE OF THE
TEST.
SO THAT'S A CONUNDRUM THAT TOOK
US A WHILE BUT MANY YEARS AGO,
WE ADDRESSED THIS, THAT WE CAN
ACTUALLY -- IF YOU KNOW THE
PREVALENCE OF DISEASE, YOU CAN
PLOT IN THE -- SPACE WHICH WE
USE TO ASSESS DIAGNOSTIC TEST
POSITIVE PREDICTIVE VALUE
CRITERIA.
SO YOU CAN PLOT POSITIVE -- IF
WE PLOT POSITIVE PREDICTIVE
VALUE LINES AS WELL AS NEGATIVE
PREDICTIVE VALUE LINES AND YOU
WILL SEE US GIVING IN THE
EXAMPLE BELOW, IF YOU SAY I WANT
TO ENRICH THE POSITIVE
PREDICTIVE VALUE OF 13% IN THIS
CASE, THERE IS A SET OF
SENSITIVITY AND SPECIFICITY OF
DATA WHICH WILL GIVE YOU THE
LINE, THE SLOPE OF THIS LINE
CHANGES DEPENDING ON THE
PREVALENCE OF THE DISEASE
BEFORE, SO THAT'S THE P IN THE
LITTLE TABLES.
SO FOR 3% OF PREVALENCE DISEASE
PRE-TEST, TO MEET POSITIVE
PREDICTIVE VALUE CRITERION, YOU
NEED TO CROSS THAT LINE.
THE VERTICAL LINE.
YOU SEE THE SLOPE CHANGING WITH
PREVALENCE OF DISEASE CHANGING
BEFORE TEST.
IT'S EASY TO -- FROM THE STANCE
OF IF YOU HAVE LOW PREVALENT
DISEASE, IT'S MORE EFFORT TO
ENRICH THEM TO A CERTAIN
RISK --.
SO IF YOU BRING THIS BACK TO
THIS DATA FROM WELLER, AND WE
ALL AGREE, HAVING A RISK GROUP
WITH 15% RISK IS GOOD ENOUGH TO
SATISFY WOMEN TO ASPIRIN,
IMAGINE HOW YOU HAVE A TEST
AVAILABLE TO YOU TO PREECLAMPSIA
RISK EARLY IN PREGNANCY, YOU
COULD NOW DEFINE DELIVERY FOR
WOMEN WHICH HAVE A DIFFERENT
RISK PROFILE AT THE BEGINNING OF
THE PREGNANCY, TESTS WHICH GIVE
YOU THE SAME FALSE TEST
PROBABILITY OF 15%.
SO ON THE LEFT, YOU SEE ALL THE
PREGNANCIES IN 2019, THERE WILL
BE MORE THAN HALF A MILLION WILL
HAVE NO RISK FACTORS, AND THE
PREVALENCE OF GESTATIONAL
HYPERTENSION IN THAT GROUP, THAT
WOULD BE 4.4%.
IF YOU WANT TO ENRICH THEM TO
HIGH RISK GROUP OF 15%, WHICH
ARE ALL HAPPY TO GIVE THEM
ASPIRIN, THEN THAT MEANS THAT'S
YOUR ROCK CURVE WOULD MEET THAT
LINE HERE AT THE PPV LINE, SAY
ABOUT SENSITIVITY, 70% IS
SPECIFICITY, 84%, YES, SO BY
THRESHOLDING YOUR RISK SCORE AT
THAT POINT, YOU CREATE A RISK
GROUP WITH THE SAME RISK AS YOU
WOULD HAVE IN A HIGH RISK
POPULATION.
YOU SEE THE SAME IF YOU HAVE
WOMEN WITH ONE -- MORE RISK
FACTOR, THE PREVALENCE OF
DISEASE IS 6.3%.
IF YOU WANT TO ENRICH IN THAT
GROUP YOU SEE IT IS AN EASIER
CRITERION TO MEET IN TERMS OF
SPECIFICITY, WE DON'T NEED SO
MUCH SPECIFICITY AND BY HAVING
THIS TOOL AVAILABLE AND GOING
THROUGH ESTIMATES OF PRIOR RISK
OF -- FOR TESTS YOU REALLY CAN
ENRICH WOMEN TO THE SAME LEVEL
OF RISK.
THAT'S WHAT WE'RE TRYING TO
BUILD NOW.
SO IF WE CAN GET ACCESS TO VERY
ROW BUTTS ESTIMATES OF RISK OF
PREECLAMPSIA IN TERMS OF PARITY,
SO -- WITH HISTORY OR NOT, AS
WELL AS IN FUNCTIONAL
RACE/ETHNICITY AND BMI, YOU CAN
ACTUAL WILL HAVE FOR ALL THESE
WOMEN, SAY PHENOTYPE-SPECIFIC
PRIOR RISKS, COMBINED WITH A SET
OF BIOMARKERS AND ALGORITHMS
WHICH ALLOWS YOU ACTUALLY TO FIT
NEXT TO YOUR PHENOTYPE, YOU CAN
IN A WAY PERSONALIZE THE RISK,
THEN YOU HAVE ALL THE TOOLS
AVAILABLE TO GIVE ALL WOMEN A
CREDIBLE RISK PREDICTION, SO YOU
CAN ALL ENRICH THEM TO THE SAME
RISK, POST-TEST RISK, AND THAT'S
WHAT WE ARE CURRENTLY WORKING
ON.
SO WE ARE CURRENTLY PUTTING THAT
TOGETHER SO WE'RE BUILDING THE
PROTOTYPE, LABORATORY WORKFLOW,
WHICH INVOLVES LIKE AN INTERFACE
TO COLLECT THE RIGHT INFORMATION
FROM THE WOMEN, BLOOD PRESSURE
DATA, PREGNANCY INFORMATION TO
BE ABLE TO PHENOTYPE.
WE ARE TO BUILD SAMPLES, WE MADE
CLINICAL ASSAY FOR METABOLITES
WHICH ARE RELATIVE TO THE RISK
PREDICTION.
THIS IS CLINICAL GRADE ASSAYS,
QUALITY CONTROL, THEY ARE
MANUFACTURABLE SO YOU CAN
PREDICT THEM, WITH REAGENTS YOU
CAN DELIVER THESE KIND OF
QUANTIFICATIONS.
PLACENTA GROWTH FACTOR, WE PUT
THAT TOGETHER IN A PERSONALIZED
RISK, -- AN WE SEE THESE AT THE
HIGHER LEVEL, SO EVERYBODY --
THERE IS THIS DRIVE, WE WANT TO
GET TO A.I. AND TRULY
PERSONALIZE PREDICTION, NO --
DOOG DIAGNOSTICS, BUT TO BE ABLO
DO THIS YOU NEED ACCESS TO LOTS
OF GOOD DATA.
YOU MIGHT ALREADY HAVE BIG
DATASETS, AND THE DATA -- BUT IN
TERMS OF BIOMARKERS, MOST
BIOMARKERS IS SPORADICALLY
MEASURED QUALITY OF THE DATA ARE
NOT PREDICTABLE OR TRANSPARENT
BECAUSE ESH U EVERYBODY USES THN
SYSTEMS, SO TO USE THIS KIND OF
DATASETS TO PATTERN RECOGNITION
IS PROBLEMATIC.
SO WHAT WE TRY TO DO HERE IS IF
WE ARE ABLE TO USE THE KIND OF
PHENOTYPING TO FIND BIOMARKERS
THAT FIT CERTAIN MIX PROFILES,
WE ALREADY CAN IMPROVE ON
SCREENING AS AVAILABLE NOW, THE
UNMET CLINICAL NEED IS NOW, WE
SHOULD BRING THESE THINGS TO --
IMPROVEMENTS IN CLINICAL
PRACTICE AS SOON AS POSSIBLE.
AND BY BEING ABLE TO START TO
GENERATE, SAY, BETTER RISK
PREDICTION USING PHENOTYPING, WE
MIGHT BE ABLE TO START TO BUILD
UP THE BIG DATASETS, BIOMARKERS
MEASURED IN A CONTROLLED WAY TO
CREATE THE DATA AS YOU CAN DO
MORE PERSONALIZED RISK
PREDICTION OR PERSONALIZED
DIAGNOSTICS.
SO ON THAT NOTE, THANK YOU FOR
LISTENING.
AND THEN LAST SLIDE.
AND THAT'S AN EFFORT OF LOTS OF
PEOPLE THAT ARE DEDICATED TO
THIS MISSION OF OUR COMPANY FOR
MANY, MANY YEARS.
THANK YOU.
>> THANK YOU.
THANK EVERYONE THAT GAVE A
WONDERFUL TALK DURING THIS
SESSION.
WE ARE A LITTLE BIT OVER TIME,
SO WE ARE GOING TO INCORPORATE
ANY QUESTIONS INTO THE BREAKOUT
SESSIONS THAT WE'RE GOING TO
HAVE THIS AFTERNOON AND WE ARE
GOING TO GO AHEAD AND BREAK FOR
LUNCH.
>> EVERYONE CAN TAKE YOUR SEATS,
WE'LL GET STARTED WITH THE NEXT
SESSION.
I'M SARA QUINNEY, INDIANA
UNIVERSITY, DATA MODEL RESEARCH
COORDINATING CENTER FOR THE
MATERNAL PEDIATRIC PRECISION AND
THERAPEUTICS OR MPRINT HUB.
IT'S MY PLEASURE TO SERVE AS NOT
RMODERATOR FOR SESSION THREE,
LEVERAGING A.I. AND MACHINE
LEARNING FOR DISCOVERY.
OUR FIRST SPEAKER IS FANNY
ANDERSON FROM ILLUMINA GLOBAL
HEALTH.
SHE'LL BE SPEAKING TODAY ON
GENOMICS A.I. FOR VARIANT
PREDICTION AND BIOMARKER
DISCOVERY.
FANNY?
>> THANK YOU, SARA.
OKAY.
GOOD AFTERNOON, EVERYONE.
MY NAME IS FANNY ANDERSON AND I
WORK IN GLOBAL MARKET
DEVELOPMENT AT ILLUMINA.
AND TODAY I'LL BE TALKING ABOUT
GENOMIC A.I. FOR VARIANT
PRIORITIZATION IN BIOMARKER
DISCOVERY, AND MY TALK
UNFORTUNATELY WILL NOT BE
TOUCHING ON SOME OF THE REALLY
KEY PAIN POINTS THAT WE'VE BEEN
TALKING ABOUT THIS MORNING IN
TERMS OF INTEROPERABILITY AND
GETTING CLINICAL DATA OUT OF THE
EMR OR MERGING CLINICAL GENOMIC
DATASETS, BUT I WILL BE TALKING
ABOUT SOME ADVANCES ON THE FIELD
OF TRYING TO UNDERSTAND AND
BETTER PREDICT THE CLINICAL
EFFECTS OF GENOMICS AND GENETIC
VARIANTS.
SO JUST TO SET THE STAGE THERE,
MANY OF YOU MAY HAVE HEARD OF
ILLUMINA.
I'M GOING TO TRY TO ADVANCE.
SO MANY OF YOU MAY HAVE HEARD OF
ILLUMINA.
WE'RE A PUBLIC COMPANY AND A
LEADER IN NEXT GENERATION
SEQUENCING AND ARRAY SOLUTIONS
FOR GENOMICS.
WE'RE BASED IN SAN DIEGO, SERVE
CUSTOMERS AROUND THE WORLD.
I THINK MANY OF YOU HAVE
PROBABLY ILLUMINA SEQUENCERS IN
YOUR RESPECTIVE CORE LABS AND
ILLUMINA IS PROBABLY BEST KNOWN
FOR OUR SEQUENCING INSTRUMENTS
IN CONSUMABLES BUT WE ALSO HAVE
A BIOINFORMATICS PORTFOLIO WHICH
INCLUDES A GROWING SUITE OF
GENOMIC A.I. TOOLS.
SO WE HAVE DRAGON, WHICH IS A
SECONDARY ANALYSIS TOOL AND THAT
USES MACHINE LEARNING TO IMPROVE
THE ACCURACY OF VARIANT CALLING.
WE ALSO HAVE CONNECTED
ANNOTATIONS AND THIS IS A NEW
PRODUCT THAT PROVIDES A SUITE OF
A.I. ANNOTATIONS THAT ARE ADDED
TO A GENOME IN LESS THAN ONE
MINUTE.
THAT INCLUDES PRIMATEAI-3D, AND
FINALLY WE HAVE EMEDGENE WHICH
WE PRONOUNCE IMAGINE BUT TRY TO
GET GENE IN THE SPELLING AND
THAT'S A TERTIARY SOLUTION, AND
TODAY WE'LL FOCUS ON PRIMATE
PRIMATEAI-3D AND EMEDAGAIN.
I'M GOING TO DIVE INTO A LITTLE
MORE ABOUT THE TYPES OF A.I.
THAT THEY ARE AND THEN ALSO KIND
OF THE DIFFERENT TRAINING SETS
THAT THEY USE.
PRIMA AI3D IS A DEEP LEARNING
MET YORK BASED ON PRIMATE
GENOMES AND 3D PROTEIN
STRUCTURES, THE PATHOGENICITY OF
PROTEIN CODING VARIANTS.
IMAGINE IS AN EXPLAINABLE A.I.
AND IT USES NATURAL LANGUAGE
PROCESSING AND MACHINE LEARNING
TO CURATE EVIDENCE FROM THE
LITERATURE AND PUBLIC DATABASES,
REAL WORLD PATIENT CASES, AND
IT'S LOOKING MORE HOLISTICALLY
AT A GIVEN CASE AND TRYING TO
PREDICT THE TOP 10 CANDIDATE
VARIANTS MOST LIKELY TO BE
CAUSING AN OBSERVED PHENOTYPE IN
AN INDIVIDUAL.
SO IT'S DIFFERENT FROM PRIMATE
AI-3D LOOKING AT A CASE, GIVING
THOSE TOP 10 RECOMMENDATIONS.
THE OTHER IS GIVING SINGLE
VARIANT SCORES.
SO AIL START WITH DIVING INTO
EMEDGENE AND HOW IT'S BEING USED
TODAY.
WE HAVE SEVERAL COMMERCIAL LABS
ALREADY USING MADGE, AND IT EME.
I THINK NOEL AND JASON SPOKE A
LITTLE ABOUT THIS THIS MORNING
BUT THIS CAN BE A REALLY MANUAL,
ARDUOUS PROCESS TO REVIEW THE
LITERATURE AND TRY TO CURATE
EVIDENCE AND UNDERSTAND THE
SIGNIFICANCE OF DIFFERENT
VARIANTS.
SO EMEDGENE USES A.I. TO KIND OF
EXPEDITE THAT PROCESS BUT IT'S
EXPLAINABLE IN THAT IT PROVIDES
RECOMMENDATIONS THAT ARE CLEARLY
LINKED AND TRACEABLE BACK TO THE
EVIDENCE THAT IT'S USING TO MAKE
THOSE RECOMMENDATIONS.
SO THIS IS KIND OF AN UMBRELLA
AS I MENTIONED LITERATURE
CURATION WITH NATURAL LANGUAGE
PROCESSING, IT ALSO GENERATES
A.I.-BASED KNOWLEDGE GRAPHS THAT
SHOW GENOTYPE/PHENOTYPE
CONNECTIONS, AND ESSENTIALLY IT
CAN REALLY ACCELERATE THAT
VARIANT INTERPRETATION PROCESS,
BUT IT'S NOT A BLACK BOX SO IT'S
PROVIDING THAT LINKED EVIDENCE
SO YOU CAN REALLY UNDERSTAND WHY
IT MAKES THE PREDICTIONS IT
DOES.
THIS HAS BEEN TESTED SO THIS IS
LOOKING AT A STUDY FROM BAYLOR,
SUGGESTING THAT THIS METHOD
ACTUALLY DOES WORK TO SOME
EXTENT, AND THIS WAS A STUDY
WHERE THEY TOOK 180 CASES THAT
BAYLOR HAD SOLVED AND HAD
IDENTIFIED A CAUSAL DIAGNOSTIC
VARIANT, BUT EMEDGENE WAS JUST
GIVEN THE SEQUENCING
INFORMATION, AND IN 97% OF
CASES, IT CORRECTLY IDENTIFIED
THE DIAGNOSTIC CAUSAL VARIANT
WITHIN ITS TOP 10 VARIANT
RECOMMENDATIONS.
AND THERE'S SEVERAL LABS USING
EMEDGENE FOR RESEARCH.
I'M GOING TO TALK SPECIFICALLY
ABOUT SHRINERS CHILDREN'S TODAY
AND THEY'RE BUILDING A BAY OWE
BANK THAT'S REALLY INTERESTING.
IT'S SUPPORTING OVER 10 RESEARCH
STUDIES THAT THEY'RE DOING AT
SHRINERS, SO THEY'RE COLLECTING
SALIVA SAMPLES, THEY'RE DOING
WHOLE GENOME SEQUENCING ON
ILLUMINA'S NOVA SEQX
HIGH-THROUGHPUT INSTRUMENT.
THEY'RE USING DRY AGAIN FOR DRAT
CALLING.
THIS CLINICAL GENOMIC KNOWLEDGE
BASE IS SERVING SEVERAL RESEARCH
PROJECTS INCLUDING ONE I'LL BE
TALKING A LITTLE BIT ABOUT IN
ADOLESCENT IDIOPATHIC SCOLIOSIS.
AND I CHOSE THIS EXAMPLE BECAUSE
THIS IS THE MOST COMMON FORM OF
SCOLIOSIS.
IT DISPROPORTIONATELY AFFECTS
GIRLS OR ADOLESCENT GIRLS.
IT HAS AN UNKNOWN ETIOLOGY, SO I
THINK THIS IS A REALLY GOOD
EXAMPLE WHERE IT'S NOT
NECESSARILY A CUT AND DRY RARE
DISEASE THAT WE UNDERSTAND WELL.
THIS IS SOMETHING THAT'S COMMON.
MULTIFACTORIAL BUT WE REALLY
DON'T UNDERSTAND IT TODAY.
SO RESEARCHERS AT SHRINERS ARE
USING EMEDGENE AS ONE OF THE
TOOLS TO TRY TO FIND GENETIC
PATHWAYS THAT MIGHT BE INVOLVED.
SO THEY'VE SEQUENCED OVER 150
FAMILIES THAT HAVE A CHILD WITH
IDIOPATHIC SCOLIOSIS, AND
THEY'VE IDENTIFIED CANDIDATE
VARIANTS IN 15 DIFFERENT GENES.
AND THEN THEY WORK TO TRY TO
LINK THOSE CANDIDATE VARIANTS TO
SHARE BIOLOGICAL PATHWAYS.
AND ONE OF THEIR HYPOTHESES IS
AROUND THE EPITHELIAL TO
MESENCHYMAL TRANSITION PATHWAY
THAT'S IMPORTANT IN STEM CELL
DIFFERENTIATION.
AND THEY'RE DOING A COUPLE
DIFFERENT THINGS TO VALIDATE AND
FURTHER PROGRESS THIS RESEARCH.
SO THEY DID SOME INITIAL CASE
CONTROL ANALYSIS USING ANOTHER
ILLUMINA TOOL CALLED COHORTS.
AND THIS TOOL DOESN'T USE A.I.
BUT I THINK IT'S REALLY VALUABLE
FOR BIOBANKS AND ACADEMIC
RESEARCH MORE GENERALLY BECAUSE
IT I A L ALLOWS YOU TO BUILD A D
CONTROL GROUP THAT'S GENERATED
FROM PUBLIC DATA.
SO THEY DID SOME CASE CONTROL
ANALYSIS AND HAVE THEN PLANNED
TO MOVE ON TO RNA SEQUENCING AND
THEN FUNCTIONAL STUDIES IN
ZEBRAFISH TO TRY TO FURTHER
VALIDATE THEIR CANDIDATE
VARIANTS.
WITH THE ULTIMATE GOAL OF
DISCOVERING NEW PROGNOSTIC AND
THERAPEUTIC APPROACHES.
SO I THINK THIS EXAMPLE IS
REALLY INTERESTING LIKE I
MENTIONED BECAUSE THEY ARE
TRYING TO SOLVE A PUZZLE OF A
POORLY UNDERSTOOD DISEASE AND I
THINK WE HAVE MANY OF THOSE IN
WOMEN'S HEALTH AND MATERNAL
HEALTH, AND MADGE EMEDGENE IS TD
BASED ON THE LITERATURE, PUBLIC
KNOWLEDGE BASES AND DATABASES
AND REAL PATIENT CASES THAT IS
INTERPRETED.
PRIMATE@3D IS DOING SOMETHING
VERY DIFFERENT IN KIND OF TAKING
A STEP FURTHER INTO THE UNKNOWN,
IF YOU WILL, SO PRIMATE A.I.3D
WORKS ON THE PROBLEM OF VARIANTS
OF UNKNOWN SIGNIFICANCE.
THIS IS A BIT OF A SCARY CHART
BUT OUR KNOWLEDGE ABOUT THE
CLINICAL EFFECTS OF PROTEIN
CODING VARIANTS, I'M GOING TO
FOCUS SPECIFICALLY ON MISSENSE
VARIANCE HERE IS RELATIVELY
NASCENT.
SO WE HAVE LESS THAN 200,000
MISSENSE VARIANTS THAT HAVE BEEN
CLASSIFIED IN CLINVAR EITHER AS
PATHOGENIC WITH VARYING DEGREES
OF CONFIDENCE AND LITERATURE
SUGGEST THERE IS COULD BE
MILLIONS OF VARIANTS OF UNKNOWN
SIG CAN'T, SOME OF WHICH WE HAVE
OBSERVED AND SOME WE HAVEN'T.
SO THEY HAD A HYPOTHESIS THAT WE
COULD LOOK AT PRIMATE GENOMES TO
TRY TO UNDERSTAND COMMON JEK
VARIANTS THAT HAVE BEEN
MAINTAINED OVER THE COURSE OF
NATURAL SELECTION AND THEIR
HYPOTHESIS WAS THAT IF WE SEE
COMMON VARIANTS THAT HAVE BEEN
PRESERVED OVER SEVERAL DIFFERENT
PRIMATE SPECIES AND THEN SHARED
IN HUMANS, THEY'RE UNLIKELY TO
BE PATHOGENIC BECAUSE THEY'VE
BEEN TOLERATED BY NATURAL
SELECTION FOR SO LONG.
SO AGAIN THIS IS A HYPOTHESIS.
THIS IS TRYING TO HELP US
UNDERSTAND WHAT MIGHT BE A VERY
LARGE PIE OF VUSs.
SO THEY WORKED WITH CONSERVATION
SCIENTISTS TO SEQUENCE OVER 800
PRIMATES, AND I DID FIND OUT
THAT ALMOST HALF OF THEM WERE
FEMALE, AND THEY LOOKED AT OVER
200 SPECIES THAT HAVE AN
EVOLUTIONARY HISTORY GOING BACK
100 MILLION YEARS.
THEY THEN IDENTIFIED 4 MILLION
COMMON MISSENSE VARIANTS THAT
MAY EXIST IN HUMANS, AND THEY
DID A COUPLE DIFFERENT THINGS TO
TRY TO TRIANGULATE THAT THOSE
VARIANTS WERE LIKELY BENIGN AND
THEY'RE ALL EXPLAINED IN DETAIL
IN A PAPER IN SCIENCE BUT ONE OF
THEM WAS LOOKING AT AMONGST THE
COMMON VARIANTS IN PRIMATES,
THERE WERE A SUBSET THAT HAD
BEEN CLASSIFIED IN CLINVAR WITH
HIGH DEGREE OF CONFIDENCE OF THE
2 STAR RATING OR ABOVE, AND
ALMOST 99% OF THOSE VARIANTS
WERE CLASSIFIED AS BENIGN WITH
HIGH CONFIDENCE.
SO PRIMATEAI-3D RECLASSIFIES
THOSE 4 MILLION VARIANTS SO IT'S
KIND OF TAKING A LEAP HERE,
AGAIN THIS IS ALL PREDICTION AND
TRYING TO HELP US FILTER OUT
LIKELY BENIGN VARIANTS.
BUT THIS IS ALL FOR RESEARCH
USE, CLEARLY.
SO THAT EATS INTO OUR PIE A
LITTLE BIT.
WE HAVE THESE 4 MILLION LIKELY
BENIGN VARIANTS, AND WHAT
PRIMATEAI-3D DOES TO TRY TO
UNDERSTAND THE REST OF THE
VARIANTS THAT ARE UNKNOWN IS
USING 3D PROTEIN STRUCTURE DATA.
THEY TRY TO LEARN ABOUT WHAT
TYPE OF AMINO ACID SUBSTITUTIONS
ARE TOLERATED IN THESE LIKELY
BENIGN VARIANTS AND THEIR
ASSOCIATED PROTEIN STRUCTURES
AND THEN WHEN PRESENTED WITH
UNKNOWN VARIANTS, IT'S TRAINED
ON SEVERAL DIFFERENT TASKS TO
TRY TO MAKE PREDICTIONS ABOUT
WHICH SUBSTITUTIONS WOULD BE
TOLERATED BY THE PROTEIN AND
WHICH WOULD AFFECT ITS FUNCTION
NEGATIVELY.
SO THERE'S A WHOLE PAPER THAT
EXPLAINS THIS BUT IT'S A
MULTI-LEARNING MODEL, SO BASED
ON LANGUAGE MODELS AND FILL IN
THE BLANK WITH 3D PROTEIN
STRUCTURES, AND GIVING AN
EXAMPLE AT A SINGLE GENE LEVEL
HERE, YOU CAN SEE THAT WHEN YOU
LOOK AT -- THIS IS A SINGLE GENE
THAT'S IMPORTANT IN THE CALCIUM
CHANNEL SPECIFICALLY, BUT YOU
CAN LOOK AT THE NOMAD MISSENSE
VARIANTS IN GREEN AND THEN THE
PRIMATE COMMON VARIANTS LAYERED
ON IN BLUE, AND THEN THE CLINVAR
PATHOGENIC VARIANTS THAT WE HAVE
CLASSIFIED TO DATE, SO YOU CAN
SEE PRIMATEAI-3D IS GIVING A
SCORE FOR EVERY SINGLE ONE OF
THESE VARIANTS ON A SCALE OF
BENIGN TO PATHOGENIC IN ITS
PREDICTION.
AND YOU CAN SEE IT ALIGNS WELL
WITH THE PATHOGENIC VARIANTS WE
HAVEN'T CLASSIFIED AND THEN
WHERE WE HAVE REALLY COMMON
PRIMATE VARIANTS, THOSE ARE
BENIGN BY PRIMATEAI-3D.
THIS IS A NEW TECHNOLOGY.
THESE SCIENCE PAPERS HAVE JUST
COME OUT OVER THE COURSE OF THE
LAST LESS THAN A YEAR, AND WE
DON'T HAVE ANY GREAT EXAMPLES
THAT I CAN POINT TO EXTERNALLY
OF THIS RESEARCH BEING PUBLISHED
BY CUSTOMERS OF OURS LIKE I DID
WITH THE SHINERS EXAMPLE.
THERE ARE SEVERAL CUSTOMERS THAT
ARE ACTIVELY WORKING ON USING
THIS IN THEIR RESEARCH, BUT I
WILL SHARE A LITTLE BIT ABOUT
SOME RESEARCH THAT ILLUMINA HAS
DONE TRYING TO INCORPORATE RARE
VARIANTS IDENTIFIED BY
PRIMATEAI-3D INTO POLYGENIC RISK
SCORES.
I CHOSE THIS CHANNEL BECAUSE I
THINK, AGAIN, IN THIS
CONVERSATION ABOUT MATERNAL
HEALTH AND WOMEN'S HEALTH, A LOT
OF THE DISEASES WE'RE LOOKING AT
ARE MULTIFACTORIAL, POLYGENIC,
NOT MONOGENIC DISEASES, AND SO
FOR COMMON DISEASES, POLYGENIC
RISK SCORES THEORETICALLY HOLE A
HOLD ALOT OF PROMISE, BUT HISTOY
POLYGENIC RISK SCORES HAVE BEEN
BASED ON COMMON VARIANTS THAT
ARE IDENTIFIED IN GWAS STUDIES.
THEY HAVE A HEAVY BIAS TOWARDS
EUROPEAN ANCESTRY AND OFTEN
DON'T PERFORM VERY WELL IN OTHER
ANCESTRY GROUPS.
BUT RARE VARIANTS, WHICH
PRIMATEAI-3D CAN HELP TO
IDENTIFY, OFTEN IS LARGER EFFECT
SIZES THAN COMMON VARIANTS, SO
THIS IS JUST ONE EXAMPLE HERE
LOOKING AT CHOLESTEROL LEVELS
AND YOU CAN SEE THAT THE RARE
VARIANTS WITHIN THE LIPID
PATHWAYS HAVE LARGER EFFECTS ON
LIKE THE ACTUAL DEVIATION IN
CHOLESTEROL LEVELS THAT ARE
OBSERVED.
AND THIS IS REALLY IMPORTANT
BECAUSE WHEN YOU'RE LOOKING AT
POLYGENIC RISK SCORES, BEING
ABLE TO INCORPORATE RARE
VARIANTS THAT HAVE LARGER
EFFECTS SHOULD HELP IMPROVE THE
ACCURACY AND WE USE THE UK
BIOBANK DATA TO TRY TO LOOK AT
THIS.
SO THERE WERE ABOUT 80 DIFFERENT
PHENOTYPES IN THIS PAPER THAT
WERE EXPLORED AND THIS IS AN
EXAMPLE SPECIFICALLY FOR TYPE
2 DIABETES.
SO YOU CAN SEE THE RARE VARIANT
PRS GENERATED FROM PRIMATEAI-3D
IN ORANGE, AND THEN THE COMMON
VARIANT PRS IN BLUE, AND WHAT'S
IMPORTANT HERE IS THAT AS YOU
GET TO LIKE HIGHER LEVELS OF
RELATIVE RISK ON THE X AXIS, THE
RARE VARIANT PRS IS BETTER AT
IDENTIFYING THE OUTLIER
INDIVIDUALS THAT ARE AT THE
HIGHEST RISK OF DISEASE.
SO THIS PAPER GIVES MORE DATA
AROUND LIKE THE CORRELATION WITH
ACTUAL PHENOTYPE AS WELL AS THE
PERFORMANCE ALONG OTHER ANCESTRY
GROUPS, BUT IT SHOWS PROMISE
THAT INCORPORATING RARE VARIANTS
INTO POLYGENIC RISK SCORES COULD
IMPROVE ACCURACY, COULD HELP TO
OVERCOME THE ANCESTRY BIAS THAT
WE'VE TYPICALLY SEEN AND THEN
ULTIMATELY FINDING RARE
PENETRANT VARIANTS THAT DO HAVE
REALLY LARGE EFFECT SIZES MAY BE
KEY TARGETS FOR FUTURE
THERAPIES, DIAGNOSTIC TOOLS AND
THINGS OF THAT NATURE.
SO TO SUM UP, PRIMATEAI-3D AND
EMEDGENE CAN BOTH BE USEFUL IN
RESEARCH, I AM ADMITTING THEY'RE
BOTH FOCUSED ON DNA AT THIS
POINT, DOWNSTREAM BIOLOGICAL
PATHWAYS THAT CAN THEN BE
VALIDATED IN FUNCTIONAL AND
MULTI-YOE MIBG STUDIES DOWN THE
ROAD.
AND I WANTED TO ALSO COMMENT
THAT OBVIOUSLY ARTIFICIAL
INTELLIGENCE IS ONLY AS GOOD AS
ITS TRAINING DATASET, SO
PRIMATEAI-3D IS REALLY
INTERESTING WHERE IT'S TAKING A
STEP INTO KIND OF LESS
CHARACTERIZED AREAS LOOKING AT
3D PROTEIN STRUCTURE DATA TO TRY
AND EXTRAPOLATE AND MAKE
PREDICTIONS TO KIND OF
ESSENTIALLY LIKE INCREASE WHAT
WE'RE ABLE TO UNDERSTAND BEYOND
OUR EXISTING LITERATURE AND OUR
EXISTING VERIFICATIONS BUT I
THINK IN OUR SPACE OVERALL,
GETTING MORE DATA AND
ESSENTIALLY LIKE BUILDING THOSE
DATASETS THAT A.I. CAN LEARN
FROM IN MATERNAL WOMEN'S HEALTH
IS GOING TO BE VERY IMPORTANT
WHICH IS WHY I'M SO INSPIRED TO
HEAR ALL OF YOU GUYS TALKING AND
I THINK JUST THE A.I. IS ONLY AS
GOOD AS THE TRAINING DATA CAN'T
SOLVE PROBLEMS OF NO DATA BEING
THERE.
SO THANK YOU SO MUCH.
>> THANK YOU, FANNY.
OUR NEXT SPEAKER IS DR. DIGNA
VELEZ EDWARDS, VANDERBILT
UNIVERSITY MEDICAL CENTER,
LEVERAGING PLACENTAL BIOBANKS
AND TRANSCRIPTION ATLAS TO
UNDERSTANDING MATERNAL/CHILD
HEALTH.
>> WE HAVE BEEN DOING SOME
BIOBANKING NOT TO THE DEGREE OF
EARLIER SESSION SPEAKER BUS
WE'VE BEEN USING THAT DATA TO
HELP BUILD TRANSCRIPTOME ATLASES
TO STUDY MATERNAL CHILD HEALTH
AND RISK FOR ADULT DISEASES.
LET'S SEE IF I HAVE ANY LUCK
WITH THIS.
THE ARROW WORKS.
SO AS MANY OF YOU KNOW, THE
DEVELOPMENTAL MODEL FOR DISEASE
CAUSATION THAT OUTLINED THE
CONCEPTS BEHIND DEVELOPMENTAL
ORIGINS OF ADULT DISEASE OR
DOHAD WAS FIRST DESCRIBED IN
1989, WHERE THE CORE IDEAS THAT
ADULT HEALTH MAY BE INFLUENCED
BY EXPOSURES THAT OCCUR DURING
FETAL STAGE, INFA INFANCY AND Y
CHILDHOOD HEALTH.
MATERNAL PREPREGNANCY OBESITY
HAS ALSO BEEN OBSERVED TO LEAD
TO OFFSPRING'S RISK FOR ASTHMA,
TYPE~2 DIABETES AND STROKE AMONG
OTHERS.
BECAUSE OF THIS AND THE ROLE OF
THE PLACENTA IN FETAL
DEVELOPMENT, A LOT OF RESEARCH
HAS FOCUSED ON LOOKING AT THE
RELATIONSHIP BETWEEN THE
PLACENTAL ENVIRONMENT AND
DEVELOPMENTAL ORIGINS OF ADULT
DISEASE.
THIS IS BECAUSE IN UTERO
EXPOSURES LEAD TO GENETIC
REGULATION IN PLACENTAL AND
FETAL ENVIRONMENTS AND PLACENTAL
EPIGENETIC CHANGES CAN RESULT IN
LONG TERM HEALTH EFFECTS ON
OFFSPRING.
THE PLACENTA HAS MANY ROLES THAT
I HAVE LISTED HERE, BUT
IMPORTANTLY, IT MEDIATES
NON-GENOMIC TRANSMISSION OF RISK
FOR NON-COMMUNICABLE DISEASES.
WITH REGARDS TO BANKING, AS PART
OF THE MPRINT STUDY, WE GOT
FUNDED A SUPPLEMENT WHERE WE'VE
BEEN DOING SOME PLACENTAL
BIOBANKING AT VANDERBILT TO DO
THIS WORK ON EQTLs, AS WELL AS
TO LOOK AT THE ROLE OF
MEDICATION EXPOSURES DURING
PREGNANCY.
PLACENTAL BIOBANKING HAS ITS OWN
KIND OF UNIQUE CHALLENGES IN
THAT YOU'RE REALLY TETHERED TO
THE TIMING OF DELIVERIES.
DELIVERIES DON'T ALWAYS OCCUR
DURING BUSINESS HOURS SO YOU
HAVE TO HAVE STAFFING THAT CAN
OCCUR ON WEEKENDS AND ON
EVENINGS, TIMING OF CONSENT CAN
BE A CHALLENGE, DO YOU CONSENT
AT DELIVERY WHICH SOME STUDY
DESIGNS ARE SET UP TO DO WHILE
OTHERS CONSENT DURING PREGNANCY.
STORAGE AND TRANSPORTATION OF
FRESH TISSUE OFTEN REQUIRES
REFRIGERATION NEEDS WITHIN LABOR
AND DELIVERY TO AT LEAST HAVE A
LANDING PAD FOR TISSUE WHILE IT
MAKES ITS WAY TO THE LAB.
COLLECTING TISSUE ACCORDING TO
VARIOUS NEEDS.
SEVERAL DIFFERENT EXPERIMENTS
REQUIRE DIFFERENT PRESERVATIONS
OF TISSUES, SOME FRESH, SOME NOT
FRESH, SOME PRESERVED WITH
SPECIFIC REAGENTS, ALL KIND OF
HAVE DIFFERENT NEEDS.
THERE'S ALSO INFORMATIC
LINKAGES.
SO YOU REALLY HAVE TO HAVE YOUR
INFORMATICS INFRASTRUCTURE SET
UP IN ORDER TO BLA BANK PLACENTL
TISSUE.
YOU NEED TO KNOW WHEN DOES YOUR
PATIENT ARRIVE AT L & D AND DO
YOU HAVE SOMEONE READY TO GO TO
BE ABLE TO COLLECT TISSUE AT AN
UNKNOWN TIME.
WHEN THE BABY IS DELIVERED.
SO IT REQUIRES A DEEP CONNECTION
AND PARTNERSHIP WITH LABOR AND
DELIVERY AND YOUR NURSES AT
NIGHT.
WITH REGARDS TO HOW WE'RE USING
PLACENTAL TISSUE, AS I MENTIONED
WE'RE REALLY INTERESTED IN EQTL
ATLASES.
SO MOST GENOMIC STUDIES USE
TISSUE ATLASES TO ASK SECONDARY
QUESTIONINGS FROM GWAS FINDINGS
AND LARGE SCALE GENOMICS
STUDIES.
SO FOR EXAMPLE, IS THERE
EVIDENCE OF THE GENE I
ASSOCIATED FOR MY STUDY ALSO
INFLUENCES GENE EXPRESSION WHEN
I DON'T HAVE TISSUE ON HAND FOR
THE SAMPLES I'M LOOKING AT.
SO A LOT OF STUDIES USE A
RESOURCE CALLED GTEX OR THE
GENOMIC TISSUE EXPRESSION
PROGRAM THAT HAS DEVELOPED
EXPRESSION QUANTITATIVE TRAIT
LOCI FOR SEVERAL TISSUES.
SO IT HAS IT FOR MULTIPLE TISSUE
TYPES.
IT HAS SOME REPRODUCTIVE TISSUES
BUT IT COMES WITH SOME
LIMITATIONS.
SO FOR THOSE OF YOU WHO AREN'T
AS FAMILIAR WITH GTEX, THIS IS
THE WEBSITE AND IT'S A PROJECT
THAT HAS COMPREHENSIVE RESOURCES
ON WHOLE GENOME SEQUENCING, RNA
SEQ DATA, QTL DATA FROM
APPROXIMATELY 54 NON-DISEASE
TISSUE SITES FROM APPROXIMATELY
1,000 INDIVIDUALS.
IT DOES HAVE REPRESENTATION,
SOME REPRESENTATION OF UTERUS
TISSUE, VAGINAL TISSUE, CERVIX
AND FALLOPIAN TUBES BUT NO
PLACENTA, AND THERE ARE CAVEATS
THAT A LOT ARE COLLECTED FROM
DECEASED INDIVIDUALS OR
POST-MENOPAUSAL INDIVIDUALS,
WHICH FOR THE WORK WE DO WHEN
WE'RE ASKING SPECIFIC QUESTIONS
ABOUT EXPRESSION IN TISSUE, THAT
ISN'T IDEAL.
SO THERE'S A LOT OF
CONSIDERATIONS ON THE TYPES OF
TISSUE THAT WE CAN USE FOR
STUDIES OF EQTLs FOR THE
TRAITS THAT WE'RE INTERESTED IN,
AND BIOBANKS THESE TYPES OF
TISSUES.
FOR INSTANCE UTERUS EXPRESSION
MIGHT BE IMPACTED BY TIMING
DURING THE MENSTRUAL CYCLE, IT
MIGHT HAVE MYOMETRIAL AND
ENDOMETRIAL COMPONENTS THAT
YOU'RE INTERESTED FOR YOUR
SPECIFIC PRESEARCH QUESTION.
THE PRIMARY COMPONENT OF THE
UTERUS THAT I'M INTERESTED IN IS
THE MYOMETRIUM, BECAUSE THAT'S
WHERE MOST FIBROIDS GROW AND
DEVELOP AND A LOT OF THESE
EXISTING RESOURCES HAVE
ENDOMETRIAL TISSUE WHICH IS
RELEVANT FOR MY WORK.
PLACENTAL TISSUE ALSO REQUIRES
CAREFUL EXCISION OF BOTH
MATERNAL AND FETAL COMPONENTS OF
THE TISSUE, SINCE THE GENETICS
THAT DETERMINE THE TISSUE OFF
BOTH OF THOSE SIDES HAVE
DIFFERENT ORIGINS.
AND TO DO AN ATLAS, YOU NEED
BOTH RNA AND DNA COLLECTED FOR
THE SAME INDIVIDUAL.
SO THERE'S MULTIPLE GROUPS
WORKING ON THIS INCLUDING GROUPS
HERE AND ELSEWHERE, AND THIS
PROVIDES A LOT OF OPPORTUNITIES
FOR US TO DEVELOP RESOURCE FOR
THE BROADER RESEARCH COMMUNITY.
GETTING THESE VERY CAREFULLY
CRAFTED ATLASES FROM VARIOUS
REPRODUCTIVE TISSUE TYPES.
AND THESE ATLASES PROVIDE
OPPORTUNITIES FOR A LOT OF
DIFFERENT THINGS.
SO WHAT WE DO IS WE DO WORK TO
BUILD UPON WHAT GTEX HAS DONE,
WHICH IS WE BUILD MODELS THAT
CAN HELP US PREDICT TRAIT GENE
EXPRESSION USING EQTL ATLAS WITH
LINKED GENE EXPRESSION DATA.
SO THE IDEA IS WE HAVE THESE
ATLASES AND WE CAN IMPUTE OR
PREDICT GENE EXPRESSION FROM
GENOME-WIDE DATA USING THOSE
EQTLs, AND THAT'S WHAT PEOPLE
HAVE BEEN DOING QUITE A BIT OF
TIME ACROSS OTHER TISSUE TYPES
WHO ARE INVOLVED IN THE GTEX
CONSORTIUM.
SO WE CONDUCT GENETICALLY
PREDICTED GENE EXPRESSION
ANALYSES SECONDARY TO PRIMARY
GENOME-WIDE STUDIES OR WHOLE
GENOME SEQUENCING STUDIES.
AND THE IDEA IS THAT WE CAN USE
THESE ATLASES FOR GWASs THAT
ARE DONE FOR PEDIATRIC AND ADULT
OUTCOMES TO SEE IF THERE'S ANY
RELATIONSHIP BETWEEN THESE
OUTCOMES AND PLACENTAL
EXPRESSION TO PROVIDE
POTENTIALLY NEW CANDIDATES FOR
FURTHER DEEPER FOLLOW-UP OR FOR
FRESH TISSUE COLLECTION WHERE
YOU WANT TO DO A TARGETED
HYPOTHESIS.
AND SO WHAT WE'VE BEEN DOING IS
WE'VE BEEN COLLECTING PLACENTAL
TISSUE, GETTING MATERNAL AND
FETAL COMPONENTS, LOOKING AT
SOME SINGLE CELL TYPES FROM THE
PLACENTA, ALSO GETTING BULK
TISSUE, AND WE'VE BEEN
EVALUATING THE RELATIONSHIP
BETWEEN ADULT DISEASES AND
EQTLs FROM PLACENTA TISSUE.
THE CORE IDEA IS THAT PLACENTAL
PREDICTED GENE EXPRESSION, WHEN
YOU HAVE AN EQTL ATLAS, CAN BE
USED WITH GWAS DATA FROM ADULT
INDIVIDUALS BECAUSE THEIR DNA IS
UNCHANGING, THEIR GERMLINE DNA,
SO YOU CAN PRETTY MUCH IMPUTE
AND PREDICT WHAT THE PLACENTAL
GENE EXPRESSION WAS WITH THESE
ATLASES.
SO AS I MENTIONED, SO WE'VE BEEN
DOING BANKING FOR VARIOUS TISSUE
TYPES FROM THE PLACENTA, AND
WHAT WE'RE INTERESTED IN IS
DOING ATLASES TO CONDUCT
MULTI-TRAIT EVALUATIONS OF
PLACENTAL PREDICTED GENE
EXPRESSION, SO LOOKING ACROSS
THE -- WE HAVE ALL THIS GWAS
DATA SITTING AROUND FOR VARIOUS
STUDIES, INCLUDING UK BIOBANK
THAT HAS ITS OWN DATABASE OF
GWAS DATA ACROSS MANY ICD-9
CODES AND DISEASES, AND WE WANT
TO SEE CAN WE USE THESE ATLASES
TO SEE IF THERE'S UNKNOWN
RELATIONSHIPS WITH ADULT
DISEASES AND PLACENTAL
EXPRESSION.
THAT'S KIND OF OUR BIGGER
PICTURE AND WE'VE BEEN DOING IT
FROM A SMALL SCALE AND GROWING
UP WITH IT, AND OUR SECOND GOAL
IS TO LOOK AT MEDICATION
EXPOSURES DURING PREGNANCY AND
THE PLACENTAL TRANSCRIPTOME, SO
THAT'S A SECONDARY RESEARCH
PROJECT WE'VE BEEN DOING WITH
THIS.
LOOKING AT EVALUATION OF GWAS
FROM JUG-BASED PHENOTYPES AND
LOOKING AT PLACENTAL EXPRESSION.
AND TO DO THIS WORK, WE ARE
FOLLOWING THE SAME PIPELINE AND
FRAMEWORK THAT GTEX DOES.
AND I WILL SAY VANDERBILT HAS
NANCY COX AND A LOT OF
INVESTIGATORS FROM THE GTEX
CONSORTIUM, SO WE HAVE
ACCESSIBILITY TO A LOT OF OF THE
SOFTWARE AND USE THESE PIPELINES
QUITE A BIT.
BUT THE S-PREDIXCAN USES EQTL
MODELS, SO WE'VE BUILT MODELS
FROM SOME PUBLISHED REFERENCES
FOR PLACENTAS AND HAVE DONE SOME
PRELIMINARY PILOT WORK WITH THAT
WHILE WE DEVELOP OUR ATLASES.
AND IT UTILIZES SUMMARY ST
STATISTICS FROM R REGRESSION
ANALYSIS, AND THIS CAN USE
META-ANALYSIS RESULTS, BUT WE
CAN ALSO PREDICT INDIVIDUAL
LEVEL DATA IF WE NEED TO USING
THE PARENT SOFTWARE, PREDIXCAN.
FOR THE REST OF THE
PRESENTATION, I'M JUST GOING TO
WALK YOU THROUGH ONE EXAMPLE OF
APPLYING A PLACENTAL PREDICTED
GENE EXPRESSION MODEL TO AN
ADULT DISEASE.
NOT SO MUCH FOR THE RESULTS OF
THAT STUDY BUT SO THAT YOU CAN
SEE WHAT I'M TALKING ABOUT WHEN
I'M REFERRING TO THIS KIND OF
ANALYSIS.
SO WITH THIS EXAMPLE, WE'RE
LOOKING AT ADULT OBESITY AND
BLOOD PRESSURE TRAITS.
WE LOOKED AT THIS BECAUSE
DIFFERENTIAL GENE EXPRESSION AND
DISREGULATED METHYLATION IN
PLACENTA IS ASSOCIATED WITH RISK
FOR PRE-ECLAMPSIA WE WANTED TO
SEE DOES THIS TRANSLATE TO
EFFECTS WE SEE IN ADULT OBESITY
AND ELEVATED BLOOD PRESSURE.
SO WE EVALUATED THE RELATIONSHIP
BETWEEN ADULT BLOOD PRESSURE
TRAITS, OBESITY AND PLACENTAL
GENETICALLY PREDICTED GENE
EXPRESSION WITH TISSUE PHENOTYPE
ASSOCIATIONS UNIQUE TO THE
PLACENTA.
SO WE LOOKED ACROSS ALL OF THE
GTEX TISSUES, PREDICTED GENE
EXPRESSION, THEN WE WANTED TO
SEE ARE THERE RELATIONSHIPS THAT
ARE SPECIFIC TO PLACENTAL GENE
EXPRESSION AND THESE TRAITS?
TO DO THIS, WE USED SUMMARY
STATISTICS FR THAT HAD SYSTOLIC,
DIASTOLIC AND PULSE PRESSURE
GENETIC DATA.
WE DEVELOPED A MODEL FROM A
PUBLICLY AVAILABLE EQTL ATLAS
FROM 2018 THAT WAS SPECIFIC TO
FETAL PLACENTAL TISSUE, AND WE
USED EXISTING MODELS AT THE TIME
OF THIS ANALYSIS FROM TB. TEXT
FOR SEVEN TISSUE TYPES.
NOT SEVEN TISSUE TYPES.
VERSION 7, 48 TISSUE TYPES, AND
WE APPLIED PREDIXCAN.
THE SUMMARY STEPS CAME FROM
ADULTS 18 AND OLDER.
THERE WAS APPROXIMATELY 339,000
INDIVIDUALS WITH BMI DATA WE HAD
SUMMARY STEPS ON, AND 776,000
FOR THE BLOOD PRESSURE TRAITS.
FOR THOSE WHO AREN'T FAMILIAR
WITH THESE KINDS OF PLOTS WHICH
I'M SURE A LOT OF YOU ARE
BECAUSE I KNOW A LOT OF YOU DO
GENOMIC DATA ANALYSIS, THIS IS A
MIAMI PLOT.
WHAT YOU SEE IS A MIRROR OF THE
GET WAS PLOTS ON THE BOTTOM AND
THE PREDICTED GENE EXPRESSION ON
THE TOP, AND ON THE Y --
CHROMOSOME POSITION AT THE
BOTTOM.
IN OUR BMI ANALYSES, WE FOUND 7E
TO PLACENTAL TISSUE GENE
EXPRESSION.
NOATDABLE AMONG THAT WAS THIS
ONE GENE, THAT HAD PREVIOUSLY
ASSOCIATED WITH PREECLAMPSIA AND
GESTATIONAL TROPHOBLAST DISEASE.
IN SYSTOLIC BLOOD PRESSURE
ANALYSES, WE OBSERVED FOUR
UNIQUE ASSOCIATIONS, DIASTOLIC
BLOOD PRESSURE WE OBSERVED THREE
UNIQUE ASSOCIATIONS, AND PULSE
PRESSURE, SEVEN UNIQUE
ASSOCIATIONS TO THE PLACENTA.
WHEN WE LOOKED ACROSS THESE
TISSUES, THESE TRAITS, WE SAW
WITH PULSE PRESSURE AND SYSTOLIC
BLOOD PRESSURE, THE FGFR1 GENE
WAS OBSERVED IN BOTH, AND IT HAD
ASSOCIATED PREVIOUSLY WITH
TROPHOBLAST EXPRESSION AND
PREECLAMPSIA, WHICH WE THOUGHT
WAS VERY INTERESTING.
AND IN CONCLUSION, WE WERE ABLE
TO IDENTIFY SEVERAL GENES FROM
THIS PREDICTED GENE EXPRESSION
ANALYSIS THAT WERE UNIQUE TO
PLACENTAL TISSUE ACROSS THESE
TRAITS WITH TWO NOTABLE GENES
ASSOCIATED WITH BMI, EXPRESSED
NEARLY EXCLUSIVELY IN PLACENTA
AND NEARBY ASSOCIATIONS WITH BMI
THAT HAVE BEEN ATTRIBUTED TO
OTHER GENES, PREVIOUSLY
ASSOCIATED WITH PREECLAMPSIA
RISK, AND THE FGFR1 THAT WAS
PREVIOUSLY ASSOCIATED WITH
PREECLAMPSIA ASSOCIATED WITH
THESE TWO TRAITS.
BUT THOSE RESULTS AREN'T WHAT IS
INTERESTING, IT'S JUST THE
APPROACH OF IDENTIFYING NOVEL
GENES THAT MIGHT INDICATE
INTERINDIVIDUAL VARIATION OF
GENE EXPRESSION IN PLACENTAL
TISSUE MAY PERCEIVE ONSET OF
SOME OF THESE ADULT DISEASES.
SO WHAT WE'RE CURRENTLY DOING
NOW IS BUILDING NEW ATLASES.
WE HAVE SEVERAL IN PROCESS THAT
WERE IN THE MIDDLE OF ANALYZING
WITH THE GOAL OF REDEPOSITING
INTO THESE DATABASES INCLUDING
DATABASES LIKE THOSE DESCRIBED
TODAY.
WE'RE USING THOSE TO USE
PHENOM-WIDE ASSOCIATION
APPROACHES TO BROADLY SCAN
ACROSS THESE DATABASES THAT
HAVING A GATS OF A LOT OF
GENOME-WIDE DATA TO BETTER
UNDERSTAND THE IMPACT OF
PLACENTAL EXPRESSION ON
CHILDHOOD AND ADULT DISEASES.
WE'RE DEVELOPING SOME SINGLE
CELL EQTL ATLASES CURRENTLY
WORKING WITH FETAL
CYTOTROPHOBLAST MODELS THAT WE
ARE ALMOST DONE DEVELOPING AND
WE'RE PLANNING ON USING ALL OF
THIS DATA TO ALSO ASSESS WITH
PATHWAY METHODS WHETHER THERE'S
MECHANISMS THAT ARE COMMON
ACROSS TRAITS WITH REGARDS TO
PLACENTAL PREDICTED GENE
EXPRESSION.
THAT'S JUST KIND OF A SUMMARY OF
HOW WE'RE APPLYING SOME OF THESE
TOOLS AND DEVELOPING TOOLS WE
WANT TO MAKE PART OF THE BROADER
RESEARCH COMMUNITY.
I'D LIKE TO ACKNOWLEDGE MY
RESEARCH TEAM, AND THAT'S MY
PRESENTATION.
>> THANK YOU.
OUR NEXT SPEAKER IS DR. NIMA
AGHAEEPOUR FROM STANFORD
UNIVERSITY.
HE IS GOING TO BE SPEAKING ON
A.I.-DRIVEN INTEGRATION OF OMICS
AND HER DATA FOR MATERNAL AND
CHILD HEALTH.
>> THANK YOU FOR HAVING ME.
OUR HEALTHCARE SYSTEMS ARE
CURRENTLY FRAGMENTED.
WE HAVE OUR OBs WHO TAKE CARE
OF THE MOMS AND ONCE THE BABY IS
BORN WE HAVE THE NEONATOLOGIST
AND PEDIATRICIANS COMING BUT
SCIENTIFICALLY WE KNOW WE NEED
TO STUDY THE MOTHER AND THE BABY
AS A DYAD, AS ONE UNIT, AND THAT
IS WHAT OUR LAB DOES.
WE ARE PHYSICALLY LOCATED
BETWEEN THE CHILDREN'S HOSPITAL
AND ADULTS' HOSPITAL, AND WE USE
VARIOUS MACHINE LEARNING AND
A.I. TECHNIQUES AS WELL AS
BIOLOGY TO STUDY MATERNAL AND
CHILD HEALTH AS A SINGLE UNIT.
FROM A TECHNOLOGY PERSPECTIVE,
WE ALSO ARE AT THE CROSSROADS OF
VARIABLE DEVICES, PHENOTYPICAL
INFORMATION FROM ELECTRONIC
HEALTH RECORDS AND MULTI-OMICS
ANALYSIS.
I'M GOING TO GIVE YOU AN
OVERVIEW OF ALL OF THAT.
ONE OF THE EARLIEST STUDIES THAT
WE DID WAS FOCUSED ON JUST
DEFINING NORMAL DYNAMIC CHANGES
DURING THE COURSE OF PREGNANCY,
BECAUSE IF YOU DON'T UNDERSTAND
NORMAL, YOU CAN'T UNDERSTAND
ABNORMAL.
THIS WAS A SINGLE CELL TYPE
ASSAY USING AN AMPED UP FLOW --
TO MEASURE MILLIONS OF CELLS PER
PATIENT.
BUT THESE CELLS DON'T LIVE IN
ISOLATION.
THEY INTERACT WITH OTHER BUY
LOGICAL MODALITIES.
THEY INTERACT WITH CELL FREE
TRANSCRIPTOMICS WHICH YOU'VE
HEARD ABOUT TODAY, PROTEOMICS
DATA, METABOLOMICS, VARIOUS
ASPECTS OF THE IMMUNE SYSTEM AT
A SINGLE CELL LEVEL, MICROBIOME
DATA AND PLASMA AND SERUM
CYTOKINES.
WHEN YOU TAKE A COHORT OF
PREGNANT WOMEN AND YOU LOOK AT
MULTI-OMICS DATASET LIKE THIS,
THE FIRST QUESTION IS WHAT
CORRELATES WITH WHAT, AND IT
TURNS OUT THAT A LOT OF THINGS
CORRELATE WITH EACH OTHER.
IT'S NOT PARTICULARLY USEFUL.
YOU HAVE TO GO INTO MORE
SYSTEMATIC PREDICTIVE MODELING
TO FIND SOMETHING.
IF YOU THROW ALL OF THESE INTO A
LINEAR MODEL WITH A GOAL OF
ESTIMATING GESTATIONAL AGE AS A
SURROGATE FOR PROGRESSION OF
PREGNANCY, IT TURNS OUT THAT
MOST OF THE FEATURES THAT GET
SELECTED ARE COMING EITHER FROM
THE CELL FREE RNA DATASET OR THE
MICROBIOME DATASET.
THIS WAS SURPRISING TO US
BECAUSE SOME OF OUR OTHER ASIS
WE EXPECTED ARE MORE EXPENSIVE,
MORE COMPLEX, HAVE MORE PRIOR
KNOWLEDGE, WE EXPECTED THEM TO
DO BETTER.
IT TURNS OUT THAT SIZE IS
IMPORTANT.
THESE LARGER MODALITIES -- IT'S
NOT JUST SIZE.
EVEN IF YOU GO BACK AND ADJUST
FOR SIZE, IT TURNS OUT THAT IT'S
NOT ENOUGH BECAUSE THE
MODULARITY OF THESE DATASETS ARE
ALSO DIFFERENT.
SOME OF THESE SMALL BUT HIGHLY
TARGETED CAREFULLY CURATED
DATASETS EVEN THOUGH THEY'RE
SMALL, THEY HAVE A LOT MORE
INFORMATION CONTENT IN THEM.
YOU NEED MORE PRINCIPAL
COMPONENTS TO MEASURE 90%
VARIANTS.
IT'S ONE THING TO MEASURE THE
SAME PATHWAY USING GENE AFTER
GENE, IT'S ANOTHER THING TO
DESIGN A CAREFUL ASSAY THAT
MEASURES THE KEY END POINTS OF
THE PATHWAYS.
SO A LOT OF THE WORK IN MY LAB
IS FOCUSED ON HOW DO WE BUILD
MACHINE LEARNING ALGORITHMS THAT
CAN PULL INFORMATION ACROSS
VARIOUS LAYERS OF BIOLOGY AND
DON'T GET OVERRUN BY SIZE
MODULARITY OR OTHER
CHARACTERIZATIONS, AND THAT I
ALLOWS US TO BUILD MODELS THAT
CAN LOOK AT THE CONTRIBUTION OF
EACH OF THESE DIFFERENT
MODALITIES AND IMPORTANTLY PUT
THEM TOGETHER IN A WAY THAT CAN
HARMONIOUSLY INCREASE PREDICTIVE
POWER.
NOW THIS WAS OUR VERY FIRST
STUDY JUST 30 PREGNANT WOMEN AT
STANFORD.
NEXT WE PARTNERED WITH THE GATES
FOUNDATION TO SCALE THIS UP TO
LOW AND MIDDLE INCOME COUNTRIES,
WE WENT TO FIVE COUNTRIES IN
SOUTHEAST ASIA AND AFRICA, AND
WE WENT UP FROM 33 PATIENTS NOW
TO 80 PATIENTS WITH THE GOAL OF
BUILDING A PREDICTIVE MODEL FOR
PRETERM.
AND IT TURNS OUT THAT WE WERE
PRETTY SUCCESSFUL.
WE WERE ABLE TO PREDICT PRETERM
BIRTH USING A PLASMA SAMPLE
DRAWN IN THE FIRST TRIMESTER OF
PREGNANCY ALONE.
THE MODEL IS LOOKING AT A
PATHWAY MEASURED USING THE LCMS
METABOLOMICS PATHWAY NEXT TO THE
GROIT FACTOR IN BLOOD, IN
PLASMA, GCSF, REALLY A CLASSIC
TEXTBOOK MODULE OF PROTEINS.
AFTER THAT WE WERE ABLE TO SCALE
THIS UP NOW TO 250 PATIENTS, AND
WE WERE ABLE TO INTEGRATE IT
WITH EPIDEMIOLOGY LEVEL
INFORMATION, WHICH WE HAD ON
TENS OF THOUSANDS IN THE SAME
COUNTRIES, WE WERE ABLE TO SHOW
THAT NOT ONLY CAN WE PREDICT
PRETERM BIRTH BUT WE ARE ALSO
ABLE TO FIND SUBTYPES OF PRETERM
BIRTH THAT HAVE DIFFERENT
CHARACTERISTICS.
FOR EXAMPLE, PRETERM BIRTH
THAT'S DRIVEN BY HIGH BMI IS
BIOLOGICALLY COMPLETELY
DIFFERENT FROM PRETERM BIRTH
THAT IS DRIVEN BY POOR
NUTRITIONAL STATUS IN THE
MOTHER.
THIS CONFIRMS WHAT WE HAVE KNOWN
FOR A WHILE THAT PRETERM BIRTH
IS JUST A SYMPTOM -- IT'S A
COLLECTION OF CAUSES, NOT JUST
ONE CAUSE.
NOW WE HAVE DONE THE SAME THING
IN PREECLAMPSIA, A VERY SIMILAR
STORY YOU START FROM A MULTI-YOE
MIX DATASET, YOU NARROW IT DOWN
TO A SMALL URINE BASED AHSIEH
THAT CAN PREDICT PRE PREECLAMPSN
THE FIRST TRIMESTER OF PREGNANCY
BUT THAT'S NOT REALLY NEWS TO
THIS AUDIENCE.
THE NEXT STEP IS HOW DO YOU GO
BEYOND PREDICTION AND START
MODULATING THESE BIOLOGICAL
FINDINGS?
ONE WAY IS TO TAKE THE
PHARMACEUTICAL APPROACH WHICH
COMES WITH TOXICITY AND LOTS OF
EXPENDITURE AND IT MAY OR MAY
NOT WORK, BUT ONE OF THE AREAS
THAT I'M VERY INTERESTED IN IS
MODIFIABLE FACTORS.
WORKING WITH OUR COLLEAGUES AT
THE PREMATURITY RESEARCH CENTER
IN WASH-U, WE PUT WEARABLE
DEVICES ON MORE THAN 1500
PREGNANT WOMEN, AND WE TRACKED
THEIR PHYSICAL ACTIVITY AND
SLEEP DURING THE COURSE OF
PREGNANCY.
AND WE THREW ALL OF THAT INTO A
FANCY A.I. MODEL WITH INCEPTION
BLOCKS WITH THE GOAL OF SEEING
IF WE CAN BUILD A MODEL THAT CAN
TELL US HOW PREGNANT SOMEBODY IS
BY LOOKING AT THE SMART WATCH
DATA ALONE.
IT TURNS OUT WE CAN.
THIS IS GESTATIONAL AGE,
ESTIMATED GESTATIONAL AGE, WORKS
PRETTY WELL.
BUT THERE ARE THESE WOMEN WHO
LOOK VERY PREGNANT BY A.I. --
AND THE OPPOSITE, THEY'RE MOVING
A LOT AND SLEEPING WELL.
THE FIRST GROUP HAS AN ODDS
RATIO AND THE SECOND IS .5
PRETERM BIRTH SO POTENTIALLY A
50% REDUCTION IN PRETERM BIRTH
RATES, AND THE BEAUTIFUL THING
ABOUT THIS IS THAT WE HAVE A
BIOBANK FOR EVERY SINGLE ONE OF
THESE SAMPLES, WE ARE NOW
BUILDING THE OBVIOUS MODELS THAT
WE NEED TO BE BUILDING,
CONNECTING SLEEP TO PHYSICAL
ACTIVITY TO ELECTRONIC HEALTH
RECORDS, PREGNANCY OUTCOMES, MA
TABLEAU MIX AND PROTEOMICS TO
SEE IF WE CAN COME UP WITH A WAY
TO STIMULATE IN THE RIGHT
DIRECTION.
MOVING ON, PRETERM BIRTH ITSELF
IS TEE FINED AS GESTATIONAL AGE
UNDER 37 WEEKS, AND AS A
COMPUTER SCIENTIST, I HAVE TO
GOOGLE THIS ALL THE TIME, I
COULDN'T REMEMBER IT.
I ASSUMED THAT THERE IS A
MEDICAL OR BIOLOGICAL REASON
BEHIND IT.
IT TURNS OUT THAT IT COMES FROM
HISTORIC STUDIES, 50 YEARS AGO
IN GERMANY, THEY FIGURED OUT
THIS IS WHERE PRETERM BIRTH GOES
ON.
SO I STARTED THINKING THAT MAYBE
WE NEED TO REDEFINE THIS, MAYBE
WE NEED TO USE ELECTRONIC HEALTH
RECORDS TO LOOK AT WHAT WE TRULY
CARE ABOUT, WHICH IS THE HEALTH
OF THE CHILDREN, NOT SOME
ARBITRARY THRESHOLD THAT TELLS
US WHO GOES TO THE NICU AND WHO
DOESN'T.
SO WE USED A.I. TO BUILD A
BRIDGE BETWEEN THE CHILDREN'S
HOSPITAL AND THE ADULT HOSPITAL.
SO WE HAD DX WITH THESE WOMEN
LONG BEFORE THEY WERE EVEN
PREGNANT AND WE HAD LONG TERM
FOLLOW-UP ON THE NEWBORNS FROM
THE CHILDREN'S HOSPITAL.
SO YOU INITIALLY HAVE THE
MOTHER'S ELECTRONIC HEALTH
RECORD BEGINS MANY YEARS AGO,
THEN THE NEWBORN IS BORN, YOU
GET THEIR ELECTRONIC HEALTH
RECORD, PUT THEM TOGETHER BEFORE
YOU CAN RUN NEURAL NETWORK AND
MAKE PREDICTIONS, YOU HAVE TO
DEAL WITH THE LONGITUDAL NATURE
OF IT.
WHICH WE DO USING LONG
SHORT-TERM MEMORY NEURAL
NETWORKS, WHICH WORK JUST LIKE
YOUR BRAIN.
WHEN YOU READ A BOOK, YOU DON'T
MEMORIZE THE ENTIRE BOOK.
YOU BRING THEM TO THE FUTURE
UNTIL YOU NEED TO MAKE A
PREDICTION.
SAME THING HERE, WE CAN'T
MEMORIZE EVERYBODY'S ELECTRONIC
HEALTH RECORD, WOULDN'T FIT INTO
OUR BIG E. COMPUTER, BUT WE CAN
GENERATE HIGH LEVEL CONCEPTS
THAT HUMANS WOULDN'T UNDERSTAND,
BUT A.I. CAN BRING IT INTO THE
FUTURE UNTIL IT NEEDS TO MAKE A
PREDICTION.
I'M NOT GOING TO SHOW YOU
PERFORMANCE METRICS.
WE HAVE COMPARED WI THIS WITH AR
SCORES, YOU CAN SEE THAT IN THE
PAPERS AND IT WORKS GREAT,
OTHERWISE I WON'T BE WOULDN'T E
TELLING YOU ABOUT IT BUT HERE'S
AN EXAMPLE FROM ONE PATIENT.
NECROTIZING ANTERIOR COLITIS,
DIDN'T DIE, THAT'S GREAT, BUT
HERE IS SEPSIS.
THEY GOT SEPSIS AND HERE IS THE
PREDICTED OUT COME.
ALSO PREMATURITY AND A WHOLE
BUNCH OF OTHERS.
IMPORTANTLY, WE PREDICTED BEFORE
THE BABY WAS EVEN BORN, WHICH IS
BORDERLINE SCIENCE FICTION BUT
IT'S NOT, IT'S REAL, AND WE HAVE
VALIDATED THIS IN MULTIPLE
INDEPENDENT HOSPITALS WITHOUT
ANY INVOLVEMENT FROM US
WHATSOEVER.
THE ALGORITHM IS LOOKING AT A
WIDE RANGE OF FACTORS THAT THE
HUMAN BRAIN WOULDN'T UNDERSTAND
BUT I CAN SHOW YOU SOME OF THE
TOP ONES.
IT'S LOOKING AT INSULIN USE IN A
MOM FOR OBVIOUS REASONS BUT IT'S
EVEN LOOKING AT HISTORY OF
CHEMOTHERAPY, LONG BEFORE THE
MOTHER WAS EVEN PREGNANT.
BECAUSE OBVIOUSLY NOT MANY
PEOPLE ARE UNDERGOING
CHEMOTHERAPY DURING PREGNANCY.
IT LOOKING AT A WIDE RANGE OF
OTHER FACTORS, IMMUNE -- BUT
IT'S EVEN ABLE TO PICK UP ON
SOCIAL DETERMINANTS OF HEALTH
LIKE HOMELESSNESS, TOBACCO USE.
I DIDN'T EVEN KNOW THAT THESE
ARE AVAILABLE IN OUR EHR, THE
MODEL FORMED BY ITSELF BUT WE
TYPICALLY PUT SOCIAL DETERMINANT
OF HEALTH INTO ONE BUCKET AND WE
KNOW THAT THEY'RE ASSOCIATED
WITH PRETERM BIRTH, BUT IT TURNS
OUT THAT IF THE MOTHER WAS
HOMELESS, RISK OF PARTICULAR
MORBIDITIES GO UP LIKE
NECROTIZING ANTERIOR COLITIS,
MICROBIOME CONNECTION, IF THE
MOTHER WAS INCARCERATED, RISK OF
OTHER THINGS, NEUROCOGNITIVE
CHALLENGES GO UP, SO YOU REALLY
CAN'T PUT ALL OF THESE INTO ONE
BUCKET BUT WHAT YOU CARE ABOUT
IS PRETERM BIRTH BUT IF WHAT YOU
CARE ABOUT IS THE ACTUAL HEALTH
OF THE BABY, YOU CAN'T.
NOW PREDICTION IS NOT ENOUGH,
YOU NEED TO GO INTO
INTERVENTIONS TO CHANGE THE
OUTCOMES THAT YOU HAVE
PREDICTED.
HERE IS ONE WAY THAT WE DO IT.
WHEN A BABY IS BORN PREMATURELY,
YOU NEED TO PUT THEM -- YOU
CAN'T PUT THEM ON BREAST MILK
BECAUSE IT INCREASES THE RISK OF
ALL KINDS OF MORBIDITIES.
THEY NEED TO GET THEIR NUTRITION
THROUGH THESE IV BAGS.
WHAT GOES INTO THE IV BAGS IS
REACTIONARY AT BEST.
THEY BASICALLY SAY LOOKS LIKE
YOUR SODIUM IS TOO LOW, LET ME
GIVE YOU MORE SODIUM FOR
TOMORROW.
SO WE CAME UP WITH AN ALGORITHM
THAT TAKES THE ENTIRE PROCESS
AND OUGHT MATES IT.
SO IF YOU'RE A NEONATOLOGIST
PLACING AN ORDER, DIETITIAN
FIXING IT, PHARMACIST REJECTING
IT BECAUSE CALORIE INTAKE IS NOT
GOOD, WE HAVE AN A.I. ALGORITHM
THAT DOES IT IN A FRACTION OF A
SECOND.
AND BECAUSE THE A.I. ALGORITHM
IS AWARE OF THE OUTCOMES OF
THESE PATIENTS, THREE MONTHS
DOWN THE ROAD, IT CAN BE
PROACTIVE AND WORRY ABOUT THREE
MONTHS DOWN THE ROAD INSTEAD OF
WORRYING ABOUT THE LAB VALUES OF
TOMORROW.
SO WE HAVE TO DO A LITTLE PILOT
TO SHOW THAT IT ACTUALLY WORKS.
WE TOOK 180 PATIENTS, WE SHOWED
A NUMBER OF PHYSICIANS THE REAL
PRESCRIPTION AND THE A.I.
GENERATED PRESCRIPTION, WE
DIDN'T TELL THEM WHICH WAS
WHICH, WE ASKED THEM TO TELL US
WHICH THEY THINK IS THE BETTER
FIT FOR THE PATIENT.
THIS IS GARY KASPAROV, HIS BODY
LANGUAGE KIND OF SPEAKS FOR
ITSELF.
AND I'M GOING TO SHOW YOU A
SPONTANEOUS PHOTO FROM THE VERY
FIRST PILOT THAT WE DID, AND
FROM BODY LANGUAGE ALONE, I'M
SURE YOU CAN TELL WHAT HAPPENED,
AND WHO IS THE PHYSICIAN, WHO IS
THE A.I. SCIENTIST.
NOT ONLY CAN THEY NOT TELL WHICH
IS WHICH, BUT THEY ACTUALLY
PICKED THE A.I.-GENERATED
SOLUTION AS THE BETTER ONE
COMPARED TO THEIR OWN.
NEXT WE HAD THE A.I. SCAN
THROUGH HOSPITAL RECORDS AND
FIND INSTANCES WHERE WE THINK
THE PHYSICIANS MADE A MISTAKE
AND IN THOSE INSTANCES, RISK OF
MORTALITY GOES UP THREE TIMES.
AND WHEN WE CHART REVIEW, THESE
RB -- MISTAKES THAT HAVE
AFFECTED THESE PATIENTS.
THEN OF COURSE WE INDEPENDENTLY
VALIDATED THIS IN A SECOND
HOSPITAL IN THOUSANDS OF
PATIENTS AND IT'S WORKING THERE
AS WELL.
THIS IS MY DAUGHTER, SHE WAS
BORN A YEAR AGO AT STANFORD, AND
IT WAS A COMPLEX PREGNANCY WITH
SEVERAL WEEKS IN THE HOSPITAL,
EMERGENCY C-SECTION,
COMPLICATIONS AFTER THAT AS
WELL.
AND NOW EVERYBODY IS DOING WELL,
MY SPOUSE IS DOING FANTASTIC,
ROYA IS DOING REALLY GREAT.
BUT I REMEMBER WALKING BACK TO
MY LAB AND ASKING MY COLLEAGUES
IF THEY COULD HAVE PREDICTED
THIS BECAUSE WE HAVE FOUNDATION
A.I. MODELS THAT ARE PREDICTING
EVERYTHING AT ANY POINT IN THE
HOSPITAL.
AND WE THOUGHT THE ANSWER IS
YES, I ASKED OUR OB COLLEAGUES
IF I HAD PREDICTED THIS, COULD
YOU HAVE DONE SOMETHING ABOUT
IT, AND THE ANSWER WAS IF YOU
COULD HAVE PREDICTED THIS TWO
HOURS FASTER THAN US, WE
PROBABLY WOULD HAVE STARTED
ANTIBIOTICS SOONER, THINGS WOULD
HAVE BEEN -- SO YOU KNOW ME AT
THIS POINT, I HAVE TO DO A
LITTLE PILOT, WE TOOK FOUR
PHYSICIANS AND WE PLAYED BEDSIDE
MONITORING DATA FOR THEM AS A
MOVIE AND WE LET THEM DO CHART
REVIEWS ON EPIC.
WE GIVE THEM A BIG RED BUTTON
AND WE TELL THEM TO PRESS IT
WHENEVER THEY THINK THE PATIENT
HAS CHORIOAND THEY WANT TO START
ANTIBIOTICS.
BUT IT TAKES THEM ON AVERAGE
ABOUT 40 HOURS TO MAKE A
DIAGNOSIS, AND THERE ARE ABOUT
75% ACCURATE.
THAT'S WHERE THE A.I. IS.
THIS WAS TWO WEEKS OF LIFE.
PRETTY STRAIGHTFORWARD, LARGE
NUMBER OF LOW HANGING FRUITS
THAT WE CAN GO AFTER NOT JUST
ABOUT PREFIX FOR WELL-DEFINED --
THAT WE CAN EASILY APPLY.
THIS IS WHAT I AM SUPER EXCITED
ABOUT THESE DAYS.
TRADITIONALLY, WE HAVE LARGE
AMOUNTS OF ELECTRONIC HEALTH
RECORDS DATA.
WE CAN AFFORD TO RUN OUR OMICS
ASSAYS ONLY ON A SUBSET OF THEM.
IN FACT, WE CAN AFFORD TO ENROLL
ONLY A SUBSET OF THEM IN OUR
BIOBANKS, FORGET ABOUT RUNNING
THE ASSAYS.
SO WHAT DO WE DO WHEN WE WANT TO
COMBINE THESE TWO WORLDS?
THE EASIEST THING TO DO IS TO
SELECT THE PATIENTS FOR WHOM WE
HAVE BIOLOGICAL DATA OR WE HAVE
SAMPLES, PUT ALL OF IT INTO A
MODEL AND MAKE A PREDICTION.
THAT'S GREAT, WE HAVE BEEN DOING
THAT FOREVER.
DEFINED CASES AND CONTROLS, SOME
PEOPLE HAVE THE ICD10 CODES THAT
WE THINK THEY NEED TO HAVE AND
THERE ARE CASES, THE ONES WHO
DON'T ARE OUR CONTROLS.
BUT IN REALITY, IT DOESN'T QOIT
WORK THAT WAY.
NOBODY IS TRULY A CASE, NOBODY
IS TRULY A CONTROL.
EVERYBODY HAS THEIR BAGGAGE OFF
THE DRUGS THAT THEY HAVE TAKEN
10 YEARS AGO AND THE SURGERIES
THAT WE HAVE DONE ON THEM AND
THEIR GENETIC BACKGROUND AND THE
ENVIRONMENTAL BACKGROUND.
NOBODY IS JUST TRULY A NICE AND
CLEAN CASE THE WAY THAT YOU
WOULD DO IT IN AN ANIMAL MODEL.
ON THE OTHER HAND, WE HAVE A TON
OF PRIOR KNOWLEDGE, WE DON'T
HAVE TO START BUILDING OUR
LINEAR MODELS AND -- MODELS FROM
SCRATCH.
WE CAN TAP INTO THAT PRIOR
KNOWLEDGE.
SO WHAT WE HAVE DONE HERE IS
THAT WE BUILT A FOUNDATION A.I.
MODEL ON THE ELECTRONIC HEALTH
RECORD DATA THAT KNOWS NOTHING
ABOUT BIOLOGY.
IT PURELY PREDICTS THOUSANDS OF
OUTCOMES THAT I DON'T EVEN KNOW
WHAT THEY ARE.
BUT IT LEARNS THE CONTEXT OF THE
MEDICAL SYSTEM.
IF I BUILD A MODEL ON THE EHR
ALONE FOR WHATEVER DISEASE THAT
I'M LOOKING AT, I GET AN
ACCURACY OF 0.76.
IF I BUILT A MODEL ON MYOMIX
DATA ALONE, I GET 0.75.
IF YOU COMBINE THE TWO USING AN
A.I. MODEL TRAINED ON THOUSANDS
UPON THOUSANDS OF ELECTRONIC
HEALTH RECORDS, YOU GET AN EXTRA
11% IN ACCURACY WITHOUT SPENDING
A SINGLE DOLLAR, WITHOUT
ENROLLING A SINGLE ADDITIONAL
PATIENT.
YOU CAN HAVE A CHILD LOOK AT
YOUR BIOLOGICAL DATA OR YOU CAN
HAVE A FULLY TRAINED MEDICAL
PROFESSIONAL LOOK AT YOUR DATA.
THE FOUNDATION MODEL WE HAVE
TRAINED ON EAR RIL VANT
ELECTRONIC HEALTH RECORD IN THIS
CASE CAN HELP US MAKE BETTER
SENSE OF BIOLOGY.
I DON'T HAVE TIME TO GO INTO THE
DETAILS OF IT, BUT IT TURNS OUT
THAT EVEN THE BIOLOGICAL
FEATURES THAT IT IDENTIFIES ARE
MORE MEANINGFUL THAN A VANILLA
MACHINE LEARNING ALGORITHM THAT
JUST LOOKS AT BIOLOGY IN
ISOLATION.
THE LAST EXAMPLE THAT I WILL
SHOW YOU BUILDS ON THIS, NOW TO
GO THE OTHER WAY, IF WE TAKE A
FOUNDATION A.I. MODEL THAT IS
TRAINED ON ELECTRONIC HEALTH
RECORDS, WE CAN TAKE THAT AND
CONNECT TO BIOLOGY, CONNECT TO A
PROTEOMICS DATASET IN THIS CASE,
AND INSTEAD OF ASKING THE
FOUNDATION A.I. MODEL TO PREDICT
DISEASE, WE CAN PREDICT IT -- WE
CAN ASK TO PREDICT BIOLOGY.
SO IT TURNS OUT THAT AT THE
PRICE OF ELECTRICITY, YOU CAN
GENERATE MILLIONS UPON MILLIONS
OF PATIENTS -- APOE, FAMOUS FOR
VARIOUS REASONS, ON THE X AXIS
YOU ARE LOOKING AT THE ACTUAL
LEVELS OF THESE PROTEINS AS
MEASURED BY AN ASSAY IN PLAY MA,
ON THE Y AXIS YOU'RE LOOKING AT
THE A.I.'S PREDICTION OF THE
LEVELS OF THOSE PROTEINS WITHOUT
HAVING TO SPEND A SINGLE DOLLAR
ON IT.
NOW WE'VE BEEN ABLE TO DO THIS
SAME THING IN HUNDREDS OF
THOUSANDS OF PATIENTS AT
STANFORD, AND THEN CAN YOU GO
BACK AND BUILD MODELS ON THE
GENERATED BIOLOGICAL DATA TO
HAVE LEGITIMATE FINDINGS THAT
YOU CAN VALIDATE IN FOLLOW-UP
STUDIES AND INDEPENDENT COHORT.
THERE IS NO FREE LUNCH, THIS
WORKS ONLY IN A SUBSET OF THE
BIOLOGICAL FACTORS THAT WE ARE
INTERESTED IN, WHICH HAVE SOME
RELEVANCE TO THE CLINICAL
CONTEXT THAT WE ARE LOOKING AT,
BUT THIS IS JUST THE BEGINNING.
IN THE FUTURE, WE ARE GOING TO
GET TO A PLACE WHERE OUR AI
MODELS GENERATE WHAT THEY CAN
GENERATE, AND THEN THEY CAN
DIRECTLY TALK TO THE
BIOREPOSITORIES, DIRECTLY TALK
TO THE LABS TO GENERATE ONLY THE
PARTS THAT WE CAN GENERATE.
GRADUALLY WE ARE GOING TO GET
CLOSER AND CLOSER TO A POINT
THAT MORE AND MORE OF THESE DATA
IS GENERATED AUTOMATICALLY AND
ONLY SMALL SUBSETS ARE PAID FOR
IN A BIOLOGICAL WORLD.
LARGE GROUP OF PEOPLE TO THANK
INCLUDING TRAINEES AND I'LL SCEP
OVER THAT, INCLUDING TRAINEES,
ALUMNI, VARIOUS MENTORS AND
COLLEAGUES AT STANFORD AND OUR
FUNDING AGENCIES.
THANK YOU.
>> THANK YOU.
OUR NEXT SPEAKER IS DR. LAURA
GORRELL FROM DELOITTE.
SHE WILL BE TALKING TODAY ON
BIOMEDICAL DATA INTEROPERAB
INTEROPERABILITY: CURRENT STATE
AND FUTURE OUTLOOK.
>> HI.
THANKS, EVERYONE, AND THANKS TO
ORGANIZERS FOR INVITING US
TODAY.
SO VIVIAN WAS INVITED TO SPEAK
BUT SHE COULDN'T SPEAK SO SHE
ASKED IF I COULD TALK AND I'M
HAPPY TO PRESENT OUR WORK.
SO WE'RE GOING TO TAKE A STEP
BACK FROM SOME OF THESE AMAZING
TALKS THAT WE'VE BEEN HEARING
AND TAKE KIND OF A 10,000-FOOT
VIEW ON DATA INTEROPERABILITY,
WHERE IT'S GOING, TOOLS AT OUR
DISPOSAL.
I'LL TRY AND TALK ABOUT SOME OF
THE THEMES THAT HAVE COME UP
TODAY AND HOW THEY FIT INTO THIS
LANDSCAPE OVERVIEW.
MAYBE I CANS CAN ALSO NOT ADVAE
SLIDES.
SO I'M JUST GOING TO GIVE A
BRIEF OVERVIEW AND KIND OF LEVEL
SET ON WHAT WE MEAN BY DATA
INTEROPERABILITY.
THE FUN FACT THE WORD
INTEROPERABILITY HAS BEEN STATED
14 TIMES TODAY.
I'VE BEEN COUNTING.
AND TALK ABOUT THE CHALLENGES
THAT I THINK WE'RE ALL VERY
FAMILIAR WITH BUT SOME OF THE
NUANCES THAT GO INTO IT AND WHAT
PHASES US WHEN WE TALK ABOUT
DATA INTEROPERABILITY,
ESPECIALLY IN THE BIOMEDICAL
COMMUNITY, AND THE ROLE OF DATA
STANDARDS FOR INTEROPERABILITY
AND THE IMPACT THEY CAN HAVE ON
RESEARCH THAT I THINK MOST OF US
ARE PRETTY WELL AWARE OF, AND
THEN ALSO HOW DATA PRIVACY AND
SECURITY FIT INTO THIS AND ARE
CONSTANTLY A BALANCE.
SO I DECIDED TO START WITH THE
FAIR ACRONYM.
90% OF US HAVE HEARD OF IT AND I
THINK THERE IS AN UNSPOKEN
LETTER.
SO INTEROPERABILITY IS THE I IN
FAIR, WHICH IS THE IDEAL STATE
FOR DATA.
NO DATA IS FAIR, IT'S JUST CON
STANDLY AN IDEAL THAT WE HAVE OH
MARCH TOWARDS.
THE MISSING LETTER IS Q.
WE LS ALSO NEED QUALITY DATA.
IF YOU CAN FIND IT, ACCESS IT,
INCORPORATE IT, GREAT, BUT IF
IT'S NOT QUALITY, WHAT'S THE
POINT?
SO THE WAY THE INTEROPERABILITY
FITS INTO THIS LANDSCAPE IS THAT
IT'S REALLY LOOKING AT HOW YOU
CAN ACCESS AND CHANGE THAT DATA
AND BE ABLE TO -- IN A WAY THAT
YOU CAN USE IT.
SO THE KEY THINGS TH ARE ACCESS,
YOU NEED TO BE ABLE TO GET
THROUGH IT, WHATEVER GOVERNANCE
IS AROUND IT.
YOU HAVE TO BE ABLE TO MESSAGE
IT AND SEND IT AND BRING IT IN.
AND THEN YOU HAVE TO BE ABLE TO
ACTUALLY INTERPRET IT, AND USE
IT WITH OTHER DATA.
ONE PIECE IS USUALLY NOT TOO
DIFFICULT, BRINGING ALL FOUR OF
THOSE THINGS TOGETHER CAN BE
INCREDIBLY CHALLENGING EVEN IN
THE MODERN ERA.
SO I SPENT A LOT OF TIME MAKING
THIS SLIDE AND TRYING TO FIGURE
OUT A FIGURE THAT REALLY SPOKE
THE MESSAGE THAT I WANTED TO,
AND SO WHAT I'VE DECIDED IS THAT
THIS IS ONE IMAGE FROM A 3D CAT
SCAN.
SO MAYBE WE'RE JUST LOOKING AT A
SAGITTAL VIEW.
ON THE LEFT YOU HAVE A BUNCH OF
DIFFERENT DATA TYPES THAT COULD
BE GENERATED.
YOU COULD GO ON THIS LIST, JUST
A TOPICAL LIST, YOU COULD ADD
BIOSPECIMEN DATA THERE AT THE
BOTTOM, THAT'S WHAT WAS IN THAT
EMPTY SQUARE.
AND ALL OF THAT IS COLLECTED AND
IN ITS DIFFERENT MEANS.
IT COULD BE A TABULAR DATASET,
IT COULD BE GRAPHICAL IN NATURE,
IT COULD BE A MANHATTAN PLOT, IT
ALL HAS DIFFERENT STRUCTURES,
THEY COULD BE IMAGES, THEY COULD
BE PDFs, SO THEN YOU HAVE TO
BRING TOGETHER ALL OF THAT
DISPARATE DATA AND PACKAGE IT
TOGETHER TO FORM YOUR BIG DATA
SO YOU CAN RUN YOUR LARGE
ALGORITHMS.
AS I SAID THIS IS ONE SLICE OF
VIEW OF DATA.
THE OTHER SLICES INCLUDE
DIFFERENT ORGANIZATIONS.
HOW DO YOU GET IT FROM ONE
HOSPITAL TO ANOTHER?
HOW DO YOU GET IT OUT OF EPIC,
HOW DO YOU BRING IT TOGETHER?
IF YOU'RE IN EUROPE, HOW DO YOU
GET IT FROM THE NORDIC COUNTRIES
THAT WE COULDN'T GET DATA FROM?
RIGHT?
SO IN AMERICA, MOST BIOMEDICAL
RESEARCH IS FUNDED THROUGH THE
NIH, IT'S NATIONALIZED.
WE TALK ABOUT SHARING IT OPENLY.
BUT OUR HEALTHCARE SYSTEM IS
NOT, IT PRIVATIZED.
SO YOU END UP WITH SILOS OF DATA
THAT ARE VERY, VERY DIFFICULT TO
CROSS.
SO HOW DO YOU DO THAT?
THE CHALLENGES, ONE OF THEM, I
DON'T LIKE THE TERM LACK OF
STANDARDIZED FORMATS FOR DATA
EXCHANGE.
WE HAVE LOTS OF THEM.
THE PROBLEM IS MOST OF THEM
AREN'T COMPREHENSIVE, SOMETIMES
THEY'RE REDUNDANT, SOMETIMES
THEY'RE VERY DIFFICULT TO USE.
I'M WILLING TO BET IF I TALK TO
EACH OF YOU INDIVIDUALLY AND ASK
YOU WHAT YOUR CONFIDENCE WAS,
THAT YOU COULD IMPLEMENT A FIRE
SYSTEM TOMORROW, YOU WOULD MAYBE
LOOK AT ME A LITTLE FUNKY.
AND IT'S BECAUSE IT'S HARD,
RIGHT?
SO WE TRY TO BUILD THESE
STANDARDS TO BE COMPREHENSIVE
AND FLEXIBLE, BUT THEN BY NATURE
OF BEING FLEXIBLE, THEY'RE NOT
STANDARDIZED, BUT THEY'RE
SUPPOSED TO BE STANDARDS.
THIS SHEER VOLUME AND VARIETY,
WEE CONSTANTLY COMING UP WITH
NEW WAYS TO LOOK AT DATA AND
ADDITIONAL METADATA WE NEED TO
TRACK WITH THE DATA, IT BECOMES
VERY COMPLICATED.
AND THE COMPLEXITY OF
INTEGRATING THAT DATA FROM THE
DISPARATE SOURCES, HOW DO YOU
GET THROUGH THESE PRIVATIZED
FIREWALLS?
OF COURSE WE HAVE GOVERNANCE AND
SECURITY CONCERNS.
WE HAVE TO NOT JUST PROTECT
PATIENTS BUT WE HAVE TO PROTECT
OUR HOSPITAL'S IT
INFRASTRUCTURE, WE HAVE TO MAKE
SURE THAT WE CAN GET THE CARE TO
THE PATIENTS WHERE WE NEED IT,
BUT ALSO KEEP THE INFORMATION
FLOWING.
SO ADDRESSING THESE CHALLENGES
ARE GOING TO NECESSITATE A
ROBUST FRAMEWORK FROM DATA
STANDARDIZATION TO ADVANCING
TOOLS FOR DATA INTEGRATION, AND
IT CONCERTED EFFORT FROM ALL
STAKEHOLDERS, THAT'S EVERY
STAINING HOLDER, NOT JUST
SCIENTISTS, IT'S IT STAFF AT
HOSPITALS, IT'S DOCTORS, NURSES,
PATIENTS, PATIENT ADVOCACY
GROUPS, THEY ALL HAVE TO COME
TOGETHER TO FIGURE OUT HOW TO
BEST COME TOGETHER.
SO ONE LITTLE CHALLENGE I ALWAYS
LIKE TO ASK WHEN WE TALK ABOUT
DATA INTEROPERABILITY BECAUSE
IT'S SOMETHING WE HEAR ABOUT ALL
OF THE TIME, WHICH OF THESE
DATES IS WRIT NEN ISO8601?
NOW, EMEDGENE YOU ARE BRINGING
TOGETHER DATA FROM 100 DIFFERENT
SOURCES AND THEY ALL HAVE DATES
WRITTEN IN VARIOUS FORMS LIKE
THIS.
IT'S SUCH A SIMPLE PROBLEM, BUT
THAT'S PROBABLY A COUPLE HOURS
OF A DATA SCIENTIST'S WORK TO
LINE THOSE DATES.
WHEREAS IF YOU HAD A
PROSPECTIVELY PLANNED OR IF WE
ENCOURAGED THE PROSPECTIVE
PLANNING OF USING STANDARDS
EARLY IN DATA COLLECTION, IT
GOES AWAY AND WE ALL KNOW THAT
THE ISO DATE IS YEAR, MONTH,
DAY, WRITTEN IN THIS FORMAT.
SO WE TALK ABOUT THE ROLES OF
DATA STANDARDS AND
INTEROPERABILITY.
WE CAN TALK ABOUT PROVIDING A
COMMON LANGUAGE FOR REPRESENTING
AND EXCHANGING HEALTH
INFORMATION.
THERE'S TWO KEY CONCEPTS IN THAT
FIRST BULLET.
NOT JUST REPRESENTING BUT
ACTUALLY EXCHANGING INFORMATION,
AND WE HAVE DIFFERENT STANDARDS
TO DO BOTH AND I'LL GO INTO SOME
EXAMPLES OF THAT IN A MINUTE.
THE EFFECTIVENESS OF USING
STANDARDS CAN BE HAMPERED BY THE
INCONSISTENT IMPLEMENTATION AND
PERSISTING USE OF LEGACY
SYSTEMS.
SO YOU'VE PROBABLY HEARD OF HL7.
THERE'S HL7 V1 AND V2, AND
ACTUALLY FIRE IS BUILT -- REALLY
IT'S HL7 V3 ESSENTIALLY, IT'S
COME OUT OF THE SAME OFFICE.
SO WE TALK ABOUT FHIR, AND THEN
WE CAN TALK ABOUT LOINCs OR
THE LOGICAL OBSERVATION
IDENTIFIER NAMES AND CODES.
ALL OF THESE STANDARDS DO
DIFFERENT THINGS.
THIS EITHER REPRESENT OR TALK
ABOUT EXCHANGING DATA.
SO WHEN WE LOOK AT THIS A LITTLE
CLOSER, WE CAN LOOK AT HL7, IT'S
A RANGE OF GLOBAL STANDARDS FOR
THE TRANSFER OF CLINICAL AND
ADMINISTRATIVE HEALTH DATA
BETWEEN CLINICAL APPLICATIONS.
WHAT DOES THAT MEAN?
WELL, IT'S NOT PATIENT FOCUSED,
IT'S EPISODE OR
VISIT-BASE-FOCUSED SO IT'S
QUICKLY NOT SERVING THE NEEDS OF
OUR RESEARCHERS OR OUR
HEALTHCARE SYSTEMS, WHICH IS WHY
IT'S BEEN REVISED SO MANY TIMES.
WE HAVE DIFFICULTY WITH
EXPRESSION OF CLINICAL FINDINGS,
SIGNS AND SYMPTOMS USING HL7.
SO IT'S BECOME FAST HEALTHCARE
INTEROPERABILITY RESOURCE OR ONE
OF THE SECTIONIEST TERMS RIGHT
NOW, FHIR, WHICH IS A SET OF
RULES AND SPECIFICATION FORCE
EXCHANGING ELECTRONIC HEALTHCARE
DATA AND THAT EXCHANGING WORD IS
VERY KEY.
USING A FHIR STANDARD, YOU
CREATE A PACKET OF INFORMATION
OR A RESOURCE, A FHIR RESOURCE,
AND YOU CAN SEND INFORMATION.
SO WHAT I MEAN BY THAT IS IF YOU
HAVE A FHIR RESOURCE WHICH IS A
SET OF DATA, IT HAS A DATE IN
THERE, IT JUST ASKS YOU TO POINT
TO WHERE THE DATE IS.
IT DOESN'T SAY YOU HAVE TO USE
ISO -- THE 8061, RIGHT?
SO A MACHINE CAN RECEIVE A
MESSAGE, WHAT DATA IS GOING TO
BE IN WHAT POSITION.
SO THAT'S DIFFERENT FROM
SOMETHING LIKE A LOINC, WHERE
YOU ACTUALLY HAVE A CODE SYSTEM
FOR IDENTIFYING LABORATORY OR
CLINICAL OBSERVATIONS WHERE YOU
HAVE THAT STANDARD OF YOU KNOW
WHAT INFORMATION IT'S CONVEYING
BUT IT DOESN'T HAVE THAT
STRUCTURE INFORMATION SOG YOU
NEED BOTH.
SO WHEN YOU THINK ABOUT
STANDARDS AND START PLANNING FOR
THE USE OF STANDARDS AND
IMPLEMENTATION OF STANDARD,
THERE'S A STANDARD FOR EACH USE
AND IT REALLY IMPORTANT TO
UNDERSTAND WHAT STANDARD YOU'RE
USING AND WHY YOU'RE USING THEM,
ESPECIALLY WHEN YOU'RE COMING UP
WITH THE GOVERNANCE FOR DATA
EXCHANGE.
THE LAST EXAMPLE I'LL GIVE HERE
THAT I THINK WILL BE KIND OF AN
INTERESTING THING TO TALK ABOUT
LATER IS THE MINIMUM INFORMATION
ABOUT NEXT GENERATION SEQUENCING
EXPERIMENTS, OR MINSEQE TO
ENABLE THE UNAMBIGUOUS
INTERPRETATION AND FACILITATE
THE REPRODUCTION OF THE RESULTS
OF THE EXPERIMENT.
SO THIS IS SPECIFICALLY FOCUSED
ON RNA SEQ.
WOULDN'T IT BE AMAZING IF WE HAD
A SET OF STANDARDS TO DESCRIBE A
BIOSAMPLE WHERE WE CAN PUT
TOGETHER BIOSAMPLE INFORMATION
FROM ALL THESE AMAZING
REPOSITORIES THAT WE'VE HEARD
FROM EARLIER AND WE HAD AGREED
UPON SET OF INFORMATION THAT WE
WERE GOING TO SHARE ABOUT THOSE
BIOSAMPLES AND COULD CREATE THAT
FEDERATED SEARCH OF BIOSAMPLES.
MAYBE THERE'S SOME LESSONS
LEARNED WE CAN LAND THERE.
WHEN I TALK ABOUT STANDARDS, THE
ONE CUTE LITTLE CARTOON I ALWAYS
THINK OF, I HAVE TO SHOW IT HERE
TODAY, WHEN YOU THINK ABOUT
STANDARDS, IT'S VERY COMMON TO
GET STUCK INTO THIS TRAP.
THERE'S 14 COMPETING STANDARDS.
14 SEEMS RIDICULOUS.
WE NEED ONE.
WE NEED A UNIVERSAL STANDARD
THAT COVERS EVERY USE CASE.
RIGHT?
THIS SOUNDS AMAZING.
WELL, YOU'LL JUST END UP WITH 15
COMPETING STANDARDS.
THE ANSWER HERE IS THAT
STAKEHOLDER ENGAGEMENT.
IT'S NOT CREATING THE NEW
STANDARD, NOT REINVENTING THE
WORLD.
IT'S WORKING WITH THE
STAKEHOLDERS THAT NEED TO
IMPROVE THE SYSTEM AND LOOKING
AT WHAT'S THERE AND HOW TO
IMPROVE UPON IT.
SO ONE EXAMPLE I WANT TO GO INTO
IS THE GA4GH.
SO IS THAT STANDS FOR THE
GLOABLG ALLIANCE FOR GENOMICS
AND HEALTH.
IT WAS A NON-PROFIT FOUNDED IN
2013 REASONLY FOCUSED ON GLOBAL
INTEROPERABILITY OF GENOMIC AND
HEALTH DATA.
IT FOCUS ON BUILDING TECHNICAL
STANDARDS, POLICY FRAME WORKS,
AND THE TOOLS TO EXPAND
RESPONSIBLE VOLUNTARY AND SECURE
USE OF GENOMIC AND OTHER
HEALTH-RELATED DATA.
SO ONE OF THE THINGS THAT MAKES
THE GH4GH VERY INTERESTING IS
THEY'RE VERY INTERESTING IN THE
WAY THEY VIEW STANDARDS AND LOOK
AT DATA INTEROPERABILITY IN THE
NARROW FIELD OF GENOMICS HEALTH.
THEY HAVE A NUMBER OF PRODUCTS
THAT ARE FOCUSED ON MAKING
INTEROPERABILITY A MORE
ACCESSIBLE GOAL.
THINGS LIKE PASSPORTS FOR
CONTROL DATA ACCESS, THEY HAVE A
PROGRAM -- A DATA REPOSITORY
SERVICE FOR DATA FILE ACCESS,
DATA USE ONTOLOGY FOR STANDARD
OF LANGUAGE FOR DATA
PERMISSIONS, DATA CONNECT AND
BEACON, AND A LOT OF OTHER
WORKS.
IF THIS IS THE FIRST TIME YOU'VE
HEARD OF GA4GH, I STRONGLY
ENCOURAGE YOU TO GO TO THEIR
WEBSITE.
THERE'S A LOT OF DIFFERENT
PRODUCTS THERE THAT ARE REALLY
HELPING ANSWER THESE QUESTIONS,
AND THEY REALLY LOOK AT IT FROM
THE FULL 3D PICTURE.
SO I DON'T PROBABLY NEED TO TELL
THIS GROUP THIS BUT JUST TO
LEVELSET, THE IMPACT ON
INTEROPERABILITY ON RESEARCH IS
VAST, RIGHT?
WE CAN ACCELERATE THE PACE OF
RESEARCH AND DISCOVERY.
IF YOU CAN COMBINE DATASETS,
YOU'VE GOT MULTIMODAL DATA,
YOU'VE GOT -- WE HAVE TO BE ABLE
TO BRING THAT DATA TOGETHER.
IT ENABLES THE SEAMLESS ACCESS
TO DIVERSE DATASETS AND EXPED
EXPEDITES AND ENHANCES OUR
UNDERSTANDING OF DISEASE
MECHANISMS AND EXPEDITES -- I
PERSONALLY COME FROM A RARE
DISEASE BACKGROUND SO THE
ABILITY TO BRING DATA TOGETHER
IS CRITICAL TO UNDERSTANDING A
LOT OF THESE DISEASES WHERE WE
HAVE VERY FEW PATIENTS.
SO THE LAST MAJOR TOPIC I WANT
TO TALK ABOUT IS DATA PRIVACY
AND SECURITY.
ENSURING THIS IS A CRITICAL
ASPECT OF DATA INTEROPERABILITY
BUT IS OFTEN ON A CONSTANT
BALANCING SCALE WITH ALLOWING
SEARCH AND FIND ABLABILITY DATA.
SAFEGUARDING SENSITIVE PATIENT
INFORMATION FROM UNAUTHORIZED
ACCESS AND BREACHES WHILE
FACILITATING DATA SHARING.
THINKING ABOUT PATIENT SECURITY
AND SENSITIVE INFORMATION AND
PII AND PHI AND ALL THOSE GREAT
THINGS, WE ALSO HAVE TO THINK
ABOUT OUR IT SECURITY, OUR
HOSPITAL SECURITY, AND MAKING
SURE THAT THAT DATA STAYS
SECURE.
SO FOR ETHICAL CONSIDERATIONS,
OBTAINING PATIENT CONSENT FOR
DATA USE AND UPHOLDING THE
PRINCIPLES OF DATA MINIMIZATION
AND PURPOSE LIMITATION.
I THINK THAT LAST ONE IS
COMPLICATED TO EXECUTE.
WHEN YOU THINK ABOUT ALL THE
DIFFERENT DATA USE AGREEMENTS
YOU HAVE TO SIGN WITH ALL THE
DIFFERENT -- I THINK THE DATA
MINIMIZATION GETS LOST IN THE
SENSE OF MAKING SURE THE RIGHT
BETA IS THE RIGHT PEOPLE AT THE
RIGHT TIME FOR THE RIGHT PERIOD
OF TIME.
ALL OF THOSE THINGS HAVE TO BE
CONSIDERED WHEN COMING UP WITH A
DATA GOVERNANCE STRUCTURE.
AND SOMETIMES IT'S AN THET CAL
TO ACTUALLY SHARING AND MAKING
DATA INTEROPERABILITY BUT IT
STILL A VERY NECESSARY PIECE
THAT HAS TO BE DISCUSSED.
SO WHERE IS THE FUTURE OF
BIOMEDICAL DATA
INTEROPERABILITY?
I THINK WE'VE HAD A GREAT FEW
TALKS HERE TO TALK ABOUT OUR
VISUAL INTELLIGENCE TO HELP
STREAMLINE DATA ANALYSIS.
IT'S A REALLY POWERFUL TOOL.
IT USES A.I. TO GENERATE
SEMANTIC LAYERS OVER DATA SO YOU
CAN GIVE IT A BUNCH OF DESPER
DESPERATE -- AS YOU'RE MANUALLY
PUTTING DATA TOGETHER SAYING
THIS IS BODY WEIGHT OVER HERE
AND IT WAS CODED THIS WAY AND IT
WAS COATED IN POUNDS AND ONE IS
IN KILOGRAMS -- THAT LEARNS FROM
YOU AND START MAKING THOSE
CONNECTIONS ON ITS OWN.
IT'S NOT PERFECT BUT IT'S AN
INTERESTING TOOL AND HAS BEEN
REALLY FUN TO WORK WITH.
THE OTHER SIDE HAS IT TOO,
RIGHT?
SO AS WE ADVANCE IN OUR ABILITY
TO INTEROPERATE DATA -- THERE IS
A CONCERN RIGHT NOW WITH 3D
IMAGING.
IF YOU HAVE AN MRI, CAN YOU
RECONSTRUCT IT AND USE FACIAL
RECOGNITION SOFTWARE TO IDENTIFY
A PATIENT?
HOW COULD YOU SHARE MRI DATA IF
Y.YOU CONVOLUTE EVERY OTHER SLIE
AND TRY TO TRIP UP PATIENT
RECOGNITION.
THAT'S A REAL SECURITY PROBLEM
BEING FACED RIGHT NOW.
ONE OF THE MAIN REASONS SHARING
IMAGING DATA IS SO DIFFICULT.
BLOCKCHAIN IS A REALLY
INTERESTING PERSPECTIVE FOR
PROVIDING A SECURE -- IT'S A
VERY DIFFERENT MODEL FOR
SECURITY THAT DELOITTE HAS BEEN
WORKING AT VERY CLOSELY, MORE SO
WITH OUR PUBLIC PRIVATE PARTNERS
BUT IT IS AN INTERESTING
PERSPECTIVE ON HOW TO PROVIDE A
SECURE DATA TRANSFER.
AND THEN ONE OF MY FAVORITE
TOPICS AND WHERE WHICH -- YOU
CAN FACILITATE DATA EXCHANGE OF
HIGHLY DIVERSE AND EXPANSIVE
DATA SYSTEMS MUCH LIKE WE HAVE
IN MEDICAL RESEARCH THROUGH A
NUMBER OF DIFFERENT DATA
GOVERNANCE METHODOLOGIES.
ON THE LEFT YOU CAN SEE THIS IS
PULLED OFF A GRAPH AND AT THE
BOTTOM LEFT, YOU HAVE HIGH LOW
CENTRALIZED DATA, AND AS YOU
MOVE UP TO THE RIGHT TO A --
DECENTRALIZED GOVERNANCE OF YOUR
DATA, SO AS YOU MOVE ACROSS THE
DIFFERENT NODES IN THE DATA
MEGS, THEY'RE AT CONNECTED
THROUGH A SEMANTIC LAYER AND YOU
ALLOW THE DIFFERENT POINTS, THEY
COULD BE DIFFERENT HOSPITALS,
THEY COULD BE DIFFERENT
DEPARTMENTS WITHIN A HOSPITAL,
TO GOVERN THEIR OWN DATA BUT IN
A FRAMEWORK THAT YOU CAN STILL
BRING THAT DATA TOGETHER.
SO YOU TALK ABOUT THE VASTNESS
OF BIOMEDICAL DATA, THESE TOOLS
BECOME -- I SWORE I WAS NOT
GOING TO SAY THE WORD GEN A.I.,
YOU CAN ACTUALLY DO THIS
AUTOMATICALLY WITHOUT THE
HUMAN -- YOU'RE ALWAYS -- BUT
WITH LESS HUMAN EFFORT IN
CURATING DATA.
SO WHAT DOES THE FUTURE OF
BIOMEDICAL DATA INTEROPERABILITY
LOOK LIKE?
MODIFYING AND MATURING THE ONES
THAT WE HAVE TO MAKE THEM USEFUL
AND MEANINGFUL TO THE RESEARCH
THAT WE'RE DOING TODAY.
THEY NEED TO BE LOOKED AT WITH A
CRITICAL EYE AND REALIZED THAT
IT'S GOING TO TAKE A LOT OF WORK
TO PIM PLEMENT THESE
TECHNOLOGIES IN A MEANINGFUL,
USEFUL WAY BUT IT'S WELL WORTH
THE EFFORT.
AND THAT IS IT.
THANK YOU.
>> THANK YOU.
OUR FINAL SPEAKER FOR THIS
SESSION IS DR. REBECCA ROSEN.
SHE'S THE DIRECTOR OF THE OFFICE
OF DATA SCIENCE AND SHARING AT
THE NICHD, AND SHE'S GOING TO
GIVE US AN UPDATE ON THE NICHD
DATA STRATEGY.
>> THANK YOU SO MUCH TO OUR
COLLEAGUES AN INVOIGT INVITING O
CLOSE OUT THE PANEL BEFORE THE
BREAKOUT SESSIONS.
I'M REBECCA ROSEN.
I'M GOING TO TALK TO YOU ABOUT
SOME OF THE STRATEGIES AND
FOUNDATIONAL WORK WE ARE DOING
AMONGST THE NICHD COMMUNITY TO
SUPPORT THE SCIENCE WE'VE BEEN
TALKING ABOUT TODAY.
OUR OFFICE WAS ESTABLISHED IN
2021 AS PART OF THE NICHD
STRATEGIC PLAN 2020 VISION.
-- FOR POPULATIONS I THINK
WE'RE SEEING HERE -- [INAUDIBLE]
ACHIEVING A VISION IS TWOFOLD.
OUR MISSION IS TO, ONE, DEVELOP
SECURE AND -- ALSO ADVISING BEST
PRACTICES -- ACROSS THE RESEARCH
AND FUNDING LIFECYCLES.
>> REBECCA, I'M SO SORRY TO
INTERRUPT YOU.
WE'RE HAVING A LITTLE BIT HARD
TIME HEARING YOU, AND YOU CAN
ALSO TRY TURNING OFF YOUR CAMERA
TO RELEASE A LITTLE BIT OF
BANDWIDTH IF THAT MAY BE
HELPFUL.
>> IS THAT BETTER?
>> MUCH BETTER SPHWHR. AWESOME.
THANK YOU.
SO GOOD TIMING.
THANK YOU FOR INTERRUPTING ME.
I REALLY DO APPRECIATE THAT.
DIDN'T WANT TO BE THAT PERSON
NOT HEARD.
SO A KEY DRIVER FOR EVERYTHING
THAT WE DO IN OUR OFFICE IS NIH
POLICY FOR DATA MANAGEMENT AND
SHARING.
SO IT WENT INTO EFFECT FOR ALL
APPLICATIONS RECEIVED FOR
FUNDING TO NIH IN JANUARY OF
LAST YEAR, SO FOR ABOUT A YEAR
AND A HALF NOW, ALL RESEARCHERS
APPLYING FOR NIH FUNDING ARE
REQUIRED TO PLAN FOR HOW THEIR
DATA AND METADATA WILL BE
MANAGED AND SHARED AND DO THAT
IN THE DATA MANAGEMENT AND
SHARING PLAN.
THE ONLY OTHER RIERM FOR THE RES
THAT RESEARCHERS, ONCE THEY'RE
AWAWARDED GRANT DBD THAT THEY
COMPLY WITH NIH APPROVED PLANS.
THE POLICY LAYS OUT A REALLY
NICE SET OF EXPECTATIONS THAT
GETS US TO THE TYPES OF HIGH
QUALITY DATA THAT WE'VE BEEN
TALKING ABOUT TODAY.
RESEARCHERS ARE EXPECTED TO
MAXIMIZE DATA SHARING.
THEY'RE EXPECTED TO SHARE DATA
AND ESTABLISH REPOSITORIES AND
IN A TIMELY MANNER, EITHER AT
THE TIME OF APPLICATION OR THE
END OF THE AWARD PERIOD,
WHICHEVER COMES FIRST.
DATA SHARING IS THE ACT OF
MAKING SCIENTIFIC DATA AVAILABLE
FOR USE BY OTHERS, THE LARGER
RESEARCH COMMUNITY,
INSTITUTIONS, THE BROADER
PUBLIC.
FOR EXAMPLE, VIA AN ESTABLISHED
REPOSITORY.
AND THIS IS SOMETHING WE'RE
HEARING A LOT ABOUT TODAY.
WHERE ARE THE DATA, WHERE ARE
THE BIOSPECIMENS.
WELL, IT REALLY HELPS WHEN
THEY'RE IN AN ESTABLISHED
LOCATION THAT HAS THE RESOURCES
TO TAKE CARE OF THEM AND TO MAKE
THEM ACCESSIBLE AND FINDABLE TO
THE BROADER RESEARCH COMMUNITY.
WE ARE WORKING WITHIN OUR NICHD
DATA SHARING COMMITTEE, WHICH IS
REPRESENTATIVES FROM ALL OF OUR
SCIENTIFIC BRANCHES AS WELL AS
FROM OUR INTRAMURAL COLLEAGUES
TO GENERATE GUIDANCE FOR OUR
RESEARCHES IN DEVELOPING OUT
THEIR PLANS AND THESE ARE POSTED
ON THE ODSS WEBSITE AS TIPS.
WE REMIND OUR RESEARCHERS AND
ALSO OUR STAFF THAT GOOD DATA
MANAGEMENT AND SHARING IS
CRITICAL TO GOOD RESEARCH, IT'S
PART OF THE RESEARCH PROCESS,
IT'S NO THE A COMPL NOT A COMPLX
AND IN ORDER TO PLAN, YOU SHOULD
PLAN AT THE OUTSET AND THIS IS
THE BEAUTY OF THE POLICY, YOU'RE
WRITING YOUR PLAN AS YOU'RE
WRITING YOUR APPLICATION.
YOU'RE IDENTIFYING WHICH DATA
YOU'RE GENERATING AND WHICH HAVE
AND WHICH DATAYOU'LL BE SHARINGL
BE SHARING AND WHEN ARE YOU
SHARING THOSE DATA AND ARE YOU
USING AN ESTABLISHED REPOSITORY,
BECAUSE YOU SHOULD.
OF COURSE THAT HELPS YOU TO
IDENTIFY YOUR METADATA STANDARDS
AND IT HELPS YOU IDENTIFY OTHER
TYPES OF ACCESS.
KEY POINT HERE IS IT IS
APPROPRIATE SOMETIMES TO LIMIT
SHARING BASED ON SPECIFIC
JUSTIFIABLE LIMITATIONS, LAWS,
IRB REQUIREMENTS, ET CETERA.
WHAT'S KEY IS THAT IN WRITING
THE MANAGEMENT AND SHARING
PLANS, IT IS CLEARLY WRITTEN WHY
THERE ARE LIMITATIONS ON DATA
SHARING.
SO THAT WE, NIH AND OUR
REPOSITORIES CAN WORK TOGETHER
TO WHAT ARE PERCEIVED AND REAL
BARRIERS TO DATA SHARING.
NOW THAT WE HAVE ALL OF THESE
DATA COMING, WE KNOW THAT OUR
OFFICE HAS TO DEVELOP OUT THE
FOUNDATIONAL RESOURCE FOR
RESEARCHERS TO FIND AND USE
THOSE DATA FOR RESPONSIBLE AND
INNOVATIVE RESEARCH.
WE'VE HAD TODAY WE HAVE A NUMBER
OF EXISTING RESOURCES THAT WE
ARE NOW DEVELOPING UP AND
DEVELOPING CONNECTIONS WITH.
OUR ECOSYSTEM IS COMPRISED OF
PEOPLE, DATA, PROCESSES AND
TECHNOLOGIES, TO SUPPORT OUR
DATA SCIENCE AND SHARING NEEDS.
WE HAVE AN NICHD ECOSYSTEM
WORKING GROUP.
ALSO A DATA SHARING COMMITTEE,
IT'S COMPRISED OF OUR EXTRAMURAL
AND INTRAMURAL STAFF AND THEY'VE
DEVELOPED THESE PRINCIPLES THAT
GUIDE OUR DEVELOPMENT OF OUR
ECOSYSTEM.
ONE LEVERAGING ECK SITION
RESOURCES, AND THEN TWO, USE
HUMAN CENTERED DESIGN-BUILT FOR
REAL NEED SO THAT YOU CAN TEST
WHAT YOU BUILT AND MAKE SURE
THAT IT ADDRESSES THOSE NEEDS.
AND THE USERS WHO SHOULD BE
GIVING US THE NEEDS SHOULD BE
DIVERSE.
THIS SHOULD COME FROM OUR
RESEARCHERS, DEVELOPERS AND MANY
OTHER COMMUNITY MEMBERS.
THE WORK WE DEVELOP SHOULD BE
UTILIZING EXISTING STANDARDS.
WE'VE HEARD A LOT OF ABOUT THAT
TODAY, AND PRIVACY AND SECURITY
NEEDS TO BE CONSIDERED IN ALL
NEW WORK THAT WE DEVELOP AND
DESIGN.
SO OUR OFFICE IN COLLABORATION
WITH ALL OF THE NICHD GROUPS
THAT I'VE MENTIONED AND ALSO OUR
RESEARCHER COMMUNITY, WE HAVE
TWO PARALLEL ACTIVITIES THAT WE
ARE WORKING ON.
FIRST WE ARE ASSESSING THE NICHD
RELEVANT DATA REPOSITORIES TO
BETTER UNDERSTAND WHAT WE NEED
FOR SUSTAINABILITY, AND ALSO FOR
INTEROPERABILITY.
SO IT'S ANOTHER INTEROPERABILITY
MEASURE, YOU'LL HEAR MORE ON
THAT FROM ME TODAY.
ALSO COLLECTING AND PRIORITIZING
USER STORIES FROM OUR COMMUNITY.
SO I WILL FIRST GIVE AN OVERVIEW
OF HOW WE'RE ASSESSING THE
REPOSITORIES.
SO WE HAVE IDENTIFIED OVER 100
DATA REPOSITORIES THAT WE
CONSIDER TO BE PART OF OUR
ECOSYSTEM.
YOU'VE HEARD A FEW OF THEM
MENTIONED TODAY BUT THERE ARE
MANY MORE.
THESE ARE ALL REPOSITORIES WHERE
OUR RESEARCHERS SUBMIT OR ACCESS
DATA.
WE PULL DOWN VARIABLES FOR THIS
ASSESSMENT FROM A NUMBER OF
EXISTING DOCUMENTS, AND WE'VE
BUCKETED THEM INTO FOUR DOMAINS.
SUPPORTING THE DATA MANAGEMENT
AND SHARING POLICY, USING DATA,
THE SUSTAINABILITY OF THE
REPOSITORY, AND ALSO HAVING
GOVERNMENT SECURE DATA.
AS WE ARE ASSESSING ALL OF THESE
REPOSITORIES, AT THE SAME TIME,
WE ARE COLLECTING USER STORIES.
AND SO THESE USER STORIES ARE
BEING COLLECTED IN A STANDARD
FORMAT.
ONE OF MY COLLEAGUES, MY DEPUTY,
IS ON THE CALL TODAY AND
COLLECTING SOME OF THESE STORIES
FROM HER DISCUSSIONS.
THE USER STORIES ALLOW US TO
HEAR WHAT OUR DIVERSE USER
COMMUNITIES WANT TO BE ABLE TO
DO IN THE DATA ECOSYSTEM AND
WHY, AND WHY THEY CAN'T
CURRENTLY DO IT.
AND THESE USER STORIES DRIVE OUR
STRATEGY FOR ECOSYSTEM
IMPROVEMENTS.
SO THE FORMAT OF OUR USER STORY
IS WHAT DO YOU WANT TO DO AND
WHY CAN'T YOU DO IT TODAY?
SO AS AN EXAMPLE, AS A PROGRAM
OFFICER, I WANT TO BUILD A
CENTRAL PLACE FOR MY RESEARCHERS
TO FIND AND USE GLOBAL HIV
DATAMENT SOME OF THOSE DATA
RESIDE IN DASH, SOME ARE IMPORT,
SOME ARE IN OTHER PLACES.
SOME ARE CONTROLS.
BUT THERE'S NO SPECIFIC PORTAL I
CAN USE TO MAKE ALL THOSE
RELEVANT DATA FINDABLE.
SO HOW ARE WE GOING TO ADDRESS
THAT, WHAT ARE WE GOING TO
BUILD, WHAT ALREADY EXISTS.
AND SO WE ARE SHARING THESE
STORIES PUBLICLY ON A GITHUB
REPOSITORY AND I'LL SHARE THE
LINK BECAUSE IT JUST WENT OFF
PUBLIC TODAY.
WE ARE FINDING IN OUR USER
STORIES THEY GENERALLY POINT TO
A NEED FOR INTEROPERABILITY AT
THREE LEVELS.
SO I KNOW WE'VE HEARD A LOT WITH
DATA INTEROPERABILITY.
AS WE SEE WE DEVELOP COMPONENTS
OF THE ECOSYSTEM, WE NOTICE WE
NEED GOVERNANCE
INTEROPERABILITY, SYSTEM
INTEROPERABILITY AND DATA
INTEROPERABILITY.
WHAT WE MEAN BY GOVERNANCE
INTEROPERABILITY IS MAKING SURE
RESEARCHERS UNDERSTAND WHAT THE
RULES ARE IN ORDER TO GET AND
USE THE DATA IN DIFFERENT
SYSTEMS.
WE HEARD ENOUGH ABOUT DATA
INTEROPERABILITY SO I DON'T NEED
TO REPEAT THAT.
BY SYSTEM INTEROPERABILITY, WE
MEAN THE SYSTEMS CAN TALK TO ONE
ANOTHER USING APIs OR WEB
SERVICES IN A STANDARD LANGUAGE.
SO FOR THE REST OF THE
PRESENTATION, I'M GOING TO WALK
THROUGH ONE USER STORY FOR EACH
OF THOSE INTEROPERABILITY LEVELS
AND TALK THROUGH WHAT WE EITHER
HAVE DONE OR ARE CURRENTLY DOING
TO ADDRESS THE USER STORIES.
ON A GOVERNANCE LEVEL, THIS WAS
EARLY DAYS WHEN OUR OFFICE JUST
STOOD UP AND COVID STUDIES WERE
HAPPENING ALL ACROSS NIH.
NOW WE HEARD FROM OUR
RESEARCHERS, WE WANTED TO BE
ABLE TO COMBINE PARTICIPANT
LEVEL DATA FROM PEDIATRIC COVID
STUDIES THAT WERE BEING FUNDED
BY DIFFERENT INSTITUTES AND
STORED IN DIFFERENT DATA
REPOSITORIES.
THEY HAD A FEELING THAT THE SAME
CHILDREN BEING RECRUITED FOR
MULTIPLE STUDIES BUT THEY DIDN'T
HAVE A WAY TO KNOW BECAUSE THEY
COULD NOT SHARE PII.
SO WE HAD AN IDEA THAT PRIVACY
PRESERVING RECORD LINK J WAS A
WAY TO ACCOMPLISH THIS
TECHNICALLY BUT WE DIDN'T KNOW
ON A GOVERNANCE LEVEL IF THIS
WOULD BE POSSIBLE.
SO WE DID AN ANALYSIS OF 13
EXISTING RECORD LINKAGE
IMPLEMENTATIONS TO UNDERSTAND
WHAT OTHERS HAD DONE IN A
SIMILAR SITUATION.
AND WHAT WE DID WAS WE
IDENTIFIED A PRETTY SIMPLE THREE
BUT ACTUALLY A LITTLE MORE
DIFFICULT TO IMPLEMENT CHECKLIST
OF CONSIDERATIONS THAT ANY GROUP
OF STAKEHOLDERS NEEDS TO COME
TOGETHER AND ADDRESS IN ORDER TO
SET UP CORRECT LINKAGE
IMPLEMENTATION CHECKLISTS.
THERE IS A LINK FOR THIS AND IT
IS PUBLISHED ON OUR WEBSITE SO
I'M NOT GOING TO WALK THROUGH
THE WHOLE THING BUT PERHAPS WE
CAN REVISIT IT AT THE BREAKOUTS.
ON THE DATA INTEROPERABILITY
LEVEL, SO WE HEARD USER STORIES
VERY COMMON TO THE ONES WE'RE
HEARING TODAY.
SO I THINK YOU'LL RECOGNIZE AS A
RESEARCHER IN MATERNAL HEALTH, I
WOULD LIKE A TOOL THAT MAKES IT
EASIER TO SEARCH FOR
REPRODUCTIVE HEALTH STUDIES IN
DBGAP AND OTHER DATA
REPOSITORIES.
WHY CAN'T YOU DO IT TODAY?
WELL, THE DATA ARE NOT
STRUCTURED IN A WAY THAT THERE
CAN BE AN EXCHANGE BETWEEN
SYSTEMS.
WE ALSO HEARD A SIMILAR USER
STORY ABOUT QUERYING
BIOSPECIMENS SO YOU CAN BUILD A
TOOL THAT INDEXES THE DARK AND
OTHER MATERIAL BIOSPECIMENS, SO
UNFORTUNATELY DASH DOES NOT HAVE
AN API TO DO THAT YET SO WE HAVE
EMBARKED ON A PROJECT TO LOOK AT
THE DBG DBGAP IMPORT -- WE'LL BE
BUILDING A SIMPLE LAYER OVER
THOSE APIs AND A USER
INTERFACE TO DEMONSTRATE WHAT
CAN BE DONE WHEN MULTIPLE DATA
REPOSITORIES USED BY OUR APIs.
YOU'LL ALSO NOTICE SOME OF THE
FHIR APIs ARE NOT CONSISTENT,
SO WE WILL BE COMMUNICATING BACK
WHAT NEEDS TO BE DONE TO ENHANCE
THOSE FHIR APIs.
AND FINALLY, WE HAVE SYSTEM
INTEROPERABILITY.
SO WE'RE SEEING OUR PERINATOLOGY
RESEARCHERS -- HOLD ON A SECOND.
I'M SORRY, EVERYBODY.
MY THROAT IS CLOSING UP.
HOLD ON.
I'M SORRY ABOUT THAT.
OKAY.
SO FROM A SYSTEM PERSPECTIVE, WE
HAD A PERINATOLOGY RESEARCHER
AND THIS GOES BACK TO WHAT WE
WERE SAYING AT THE OUTSET OF THE
WORKSHOP TODAY.
WE HAVE DATA FROM THAT COHORT
POSTED IN DASH, BUT THERE'S
ANOTHER NHLBI-FUNDED COHORT THAT
IS LIVING IN BIODATA CATALYST.
NOW WE HEAR FROM RESEARCHERS
THEY WANT TO BE ABLE TO
CO-ANALYZE THE NEW MOM TO BE
COHORT DATA IN THE CLOUD WITHOUT
DOWNLOADING TO THEIR LOCAL
MACHINES.
THAT IS NOT CURRENTLY POSSIBLE
BECAUSE THE DATA REP REPOSITORIO
NOT HAVE APIs WITH MOVEMENT OF
DATA.
SO WE DEVELOPING WORK SPACES,
THIS IS AN ONGOING ACTIVITY WITH
NIH ACROSS THE NIH COLLEAGUES TO
USE STANDARD APIs FOR OUR DATA
REPOSITORIES TO EXCHANGE
AUTHENTICATION -- AS WELL AS TO
EXCHANGE DATA SO WE'RE USING THE
RESEARCHER -- SERVICE HERE AND
REPOSITORY SERVICE WE JUST HER
LAURA TALK ABOUT.
SO CONSIDERATIONS FOR T TODAY'S
WORKSHOP.
THIS GOES BACK TO WHAT AARON HAD
SAID AT THE VERY OUTSET OF THE
WORKSHOP.
WE WANT TO HEAR FROM YOU,
BUILDING MATERNAL HEALTH,
INNOVATION, KNOWLEDGE RESOURCE.
SO WITH THAT, YOU'VE HEARD ME
KIND OF WALK THROUGH THESE
STORIES ALREADY SO I WON'T
REPEAT THEM BUT AGAIN I WANT TO
THANK EVERYBODY FOR BRINGING
TOGETHER THESE FANTASTIC USER
STORIES AND FANTASTIC RESEARCH,
AND I LOOK FORWARD TO THE
BREAKOUT SESSIONS.
THANK YOU.
>> THANK YOU, DR. ROSEN.
WE HAVE ABOUT FIVE MINUTES LEFT
IN THE SESSION FOR A PANEL
DISCUSSION, IF OUR PANELISTS
WOULD LIKE TO -- IF ANYONE HAS
QUESTIONS FOR THE PANELISTS.
WE CAN SAVE QUESTIONS FOR THE
BREAKOUT SESSION OR --
>> QUICK QUESTION.
YOU MUST TALK ABOUT THE
FOUNDATIONAL A.I. MODEL FOR
MEDICAL DATA.
SO WHEN YOU SAY FOUNDATIONAL
A.I., DO YOU MEAN LABEL THE DATA
AROUND THE A.I. MODEL TO GET --
UNSUPERVISED VERSION OR
SUPERVISED VERSION?
>> WHEN I TALKED ABOUT
FOUNDATION MODELS AND THE
LANGUAGE GETS -- PEOPLE HAVE
STRONG FEELINGS ABOUT FOUNDATION
VERSUS FOUNDATIONAL AND THEY
TECHNICALLY MAY MEAN DIFFERENT
THINGS, BUT WHAT I WAS
PARTICULARLY TALKING ABOUT WAS
NOT SUPERVISED OR UNSUPERVISED,
IT WAS SELF-SUPERVISED, WHERE
JUST LIKE TRANSFORMERS, YOU
LEARN FROM THE EXISTING DATA
THAT YOU HAVE REGARDLESS OF
WHETHER YOU HAVE LABELS ON --
>> THE EMBEDDED --
>> IT HAS AN ENCODER COMPONENT
TO IT, YES.
>> I HAVE A QUESTION FOR -- I'M
SORRY, I FORGOT YOUR NAME.
SO YOU INTRODUCED TWO
A.I.-BASED -- TO PREDICT
POLYGENIC RISK OF -- IS THERE
ANY WAY LIKE -- BECAUSE SOME FOR
EXAMPLE WITH HEART DISEASE, WE
IDENTIFY SEVERAL -- MUTATIONS
BUT THE PANCREAS IS PRETTY LOW.
USING YOUR PLATFORM, IS THERE
ANY WAY YOU CAN PREDICT
POLYGENIC VARIANTS ASSOCIATED
WITH SPECIFIC TRAIT AND USING
YOUR PREDICTION, HOW APPROACH --
USE TO VALIDATE YOUR PREDICTION?
>> THANKS FOR THE QUESTION.
SO THE SCIENCE PAPER, AND I CAN
SEND TO YOU, THEY LOOKED AT
ABOUT 80 DIFFERENT PHENOTYPES IN
THE UK BIOBANK COHORT AND BUILT
RARE VARIANT POLYGENIC RISK
SCORES AND THEY HAVE
VARYING DEGREES OF ACCURACY.
THEY'RE BEST AT FINDING THE
OUTLIER INDIVIDUALS AT THE
HIGHEST LEVELS OF RISK.
I THINK IT STILL NEEDS MORE
VALIDATION BUT IT DEFINITELY WAS
A PROMISING APPROACH TO TRY TO
IMPROVE UPON AREAS WHERE WE
THINK PRSs ARE PROMISING BUT
THAT THEY'VE HAD CHALLENGES DUE
TO ANCESTRY BIAS, ET CETERA.
SO IT'S A NEW FIELD BUT I THINK
YOU CAN SEE THE PAPER AND THEN
HOPEFULLY THERE WILL BE MORE
RESEARCH COMING TO VALIDATE IT.
>> OKAY.
THANK YOU.
>> THAT WILL CONCLUDE THE
SESSION.
I BELIEVE WE HAVE A BREAK AND
THEN ZHAOXIA DO YOU HAVE MORE
INFORMATION ON THE BREAKOUTS?
>> SO WE ARE JUST FINISHING UP
ON TIME, SO I GUESS YOU STILL
HAVE A LOT OF QUESTIONS YOU CAN
SAVE INTO THE QUESTION TO THE
BREAKOUTS.
SO WE HAVE A 15-MINUTE BREAK,
SO FIRST OFF, BEFORE WE DIVE
INTO THE BREAKOUT GROUP RECAPS,
I JUST WANT TO AGAIN THANK
MELISSA, ZHAOXIA AND HANI FOR
PULLING THIS MEETING TOGETHER,
ORGANIZING IT, AND I WANT TO
THANK ALL THE SPEAKERS AND
EVERYBODY ELSE THAT TRAVELED
HERE TODAY TO LEAD TO THIS GREAT
DISCUSSION.
AND I ALSO WANT TO THANK
EVERYBODY THAT TOOK TIME OUT OF
THEIR DAY, WHETHER YOU'RE
WATCHING IT LIVE OR YOU'RE
TAKING TIME TO WATCH IT ON
VIDEOCAST, THANK YOU FOR THAT AS
WELL.
SO WHAT I'D LIKE TO DO, WE HAVE
ABOUT 29 MINUTES LEFT, SO EACH
OF THE THREE GROUP LEADERS WILL
GO THROUGH THEIR COMMENTS AND
SORT OF A SUMMARY OF WHAT THEY
HEARD, AND AGAIN, WE REALLY WANT
TO THINK ABOUT WHAT WE CAN DO
WITH WHAT WE HAVE, WHAT WE CAN
DO IN THE FUTURE, HOW WE CAN DO
THINGS BETTER, AS WELL AS ANY
RECOMMENDATIONS/THOUGHTS ABOUT
HOW WE CAN CONTINUE THIS
CONVERSATION OR CONVERSATIONS,
AND WHAT ARE THE DIFFERENT
THINGS WE CAN FOLLOW UP ON.
SO WITH THAT, I WILL TURN TO
MELISSA AND HARINA FOR THE GROUP
ONE SUMMARY.
>> OKAY.
HARINA AND I WILL TAG-TEAM THIS
HERE.
SO WITH REGARD TO EXISTING
BIOREPOSITORIES THERE IS
ADMITTEDLY A LACK OF DIVERSITY
IN MANY OF THE BIOREPOSITORIES.
SO ONE OF THE THINGS THAT WAS
DISCUSSED IS SIMPLY ACCESSING
THE PATIENTS.
ESPECIALLY IF YOU'RE LOOKING AT
OR COLLECTING SAMPLES DURING
PREGNANCY, OFTENTIMES YOU MAY
MISS SOME OF THE PATIENTS THAT
WOULD HAVE A LOWER SOCIOECONOMIC
STATUS OR NOT HAVE ACCESS TO
HEALTHCARE OR MIGHT BE IN A
RURAL ENVIRONMENT, SO YOU'RE
GOING TO MISS THE FIRST COUPLE
OF SAMPLE COLLECTIONS THAT ARE
POSSIBLE EARLIER IN PREGNANCY,
BUT IF AN ISSUE MATERIALIZES,
THEN THEY WILL SHOW UP LATER IN
THEIR PREGNANCY.
SO YOU'RE LOSING A LITTLE BIT OF
ACCESS THERE ESPECIALLY FOR
LONGITUDAL SAMPLES.
ONE OF THE WAYS TO GET AROUND
THIS IS ACTIVE COMMUNITY
ENGAGEMENT, ENGAGING IN
COORDINATORS THAT CAN SPEAK THE
LANGUAGE OF THE COMMUNITIES THAT
YOU'RE TRYING TO ACCESS, AND
ETHNIC OR RACIAL GROUPS OR
SPECIFIC POPULATIONS THAT YOU'RE
TRYING TO ACCESS AS WELL.
>> SO OTHER THINGS THAT WERE
DISCUSSED THAT HELP WITH THIS
WERE PATIENT ENGAGEMENT
INITIATIVES, HAVING TRANSLATED
MATERIALS USING A TRANSLATOR
APPROVED BY THE IRB, CONSENT
FORM AND THE RECRUITMENT
MATERIALS, ETHNICALLY DIVERSE
GROUPS COULD BE EFFECTIVE.
>> SO ANOTHER TOPIC THAT CAME UP
IS FUTURE-PROOFING YOUR
BIOREPOSITORY.
IT'S BEING TACKLED IN A COUPLE
OF DIFFERENT WAYS.
BY COLLECTING A WIDE VARIETY OF
SAMPLE TYPES, BY HAVING ALIQUOTS
THAT ARE OF A SIZE THAT IS OF
MOST UTILITY YET WILL NOT BE
WASTED THROUGH REALIQUOTING.
ANOTHER RECOMMENDATION WAS THE
USE OF A.I. OR INSILICO DATA
ANALYSIS, AND THEN GETTING
SAMPLES FOR USE AFTER THE DATA
ANALYTICS ON EXISTING DATA AND
INFORMATION THAT'S AVAILABLE.
AND THEN OF COURSE TO DO THIS,
YOU WOULD ALSO NEED ACCESS
HOPEFULLY NOT ONLY TO THE
ELECTRONIC OR MEDICAL RECORD
DATA THAT IS ASSOCIATED WITH THE
SAMPLE, BUT HOPEFULLY ACCESS TO
THE RESULTS OF ANALYSES THAT
HAVE ALREADY BEEN PERFORMED THAT
COULD LEAD YOU FOO A SPECIFIC
DIRECTION OR ANSWER CERTAIN
QUESTIONS BEFORE YOU GO IN AND
ACCESS THE SAMPLES.
THIS IS A HINDRANCE AT SOME
INSTITUTES BECAUSE THEY DO NOT
HAVE THE CAPABILITY TO HAVE DATA
DEPOSITED BACK INTO THEM FOR A
MULTITUDE OF REASONS FROM
GOVERNANCE OR JUST A LACK OF
CAPABILITY OR FUNDING TO DO SO,
WHEREAS OTHER SYSTEMS OR OTHER
ACADEMIC INSTITUTES AND
BIOREPOSITORIES THAT SPOKE TODAY
DO HAVE THE ABILITY TO REDEPOSIT
DATA BACK INTO THEIR -- ONE
EXAMPLE WAS INTO THEIR LIMB
SYSTEM, I THINK YOU CALLED IT
BIOSHARE, SO THAT ANALYTICS THAT
HAVE ALREADY BEEN PERFORMED WITH
THE DATA IN THE SAMPLES CAN BE
UTILIZED BY THE LARGER RESEARCH
COMMUNITY.
>> ANOTHER TOPIC THAT WE TAL
TALKED -- THAT WE DISCUSSED WAS
LARGE COLLECTION OF SAMPLES
THROUGH LONGITUDAL STUDIES, AND
HOW SAMPLE HOARDING IS BEING
VERY COMMON, SO UNDERSTANDING
WHAT IS THE REASONABLE LIFESPAN
OF SAMPLES IS IMPORTANT.
SO ADVERTISING RESOURCES, SO
WHAT IS AVAILABLE IS KNOWN TO
LIKE A BROADER GROUP SO THERE'S
MOST USE OF THE SAMPLES THAT ARE
BEING STORED, AND A
RECOMMENDATION WAS MADE FOR A
CENTRAL REPOSITORY FOR THE NICHD
SAMPLES THAT ARE BEING
COLLECTED.
>> SO TWO OF THE LARGEST ISSUES
THAT WERE NOTED FOR ACCESS IN
USE OF THE SAMPLES AND DATA THAT
ARE IN EXISTING BIOREPOSITORIES
IS DIFFICULTY EXECUTING MATERIAL
TRANSFER AGREEMENTS AND DATA USE
AGREEMENTS.
OFTENTIMES THERE'S NOT A
STANDARDIZED PROCESS IN MANY
PLACES, AND IT CAN GET TIED UP
IN LEGAL ON BOTH SIDES FOR QUITE
A SIGNIFICANT AMOUNT OF TIME.
ALSO STANDARD LANGUAGE FOR THE
SHARING OF GENOMIC DATA WOULD
ALSO BE OF TREMENDOUS BENEFIT.
LET ME SEE.
I THINK THAT IS -- DID I MISS
ANYTHING, HARINA?
>> NO, I JUST HAVE ONE COMMENT
BACK TO ADVERTISING THE
RESOURCES THAT ARE AVAILABLE.
A COUPLE OF INSTITUTES BROUGHT
UP HAVING OVERSIGHT COMMITTEE
THAT CONSISTS OF RESEARCHERS AND
CLINICIANS THAT CAN REVIEW THE
REQUEST THAT IS COMING IN FOR --
OR THE PROPOSAL THAT IS COMING
IN FOR THE USE OF BIOSAMPLES.
THAT'S IT.
>> QUESTIONS?
>> I'M SORRY?
>> CAN WE ASK QUESTIONS?
>> WE DON'T ACTUALLY HAVE A LOT
OF TIME.
WE HAVE 10 MINUTE PER -- IN
TERMS OF QUESTIONS, I THINK IT
WOULD BE GREAT, MAYBE SEND THOSE
IN TO THE GROUP LEADERS OR
ZHAOXIA AND MELISSA, BECAUSE WE
DEFINITELY WANT TO CAPTURE THAT
AND THINK ABOUT QUESTIONS THAT
WE CAN BRING FORWARD INTO OTHER
CONVERSATIONS.
>> THANK YOU.
SO WE WERE DISCUSSING BASED ON
THE OVERARCHING QUESTIONS AND
GUIDANCE TOPICS THAT WERE SENT
TO ME.
THERE ARE A LOT OF OVERLAPPING
THINGS, REDUNDANT THINGS WITH
WHAT I HEARD FOR GROUP TWO BUT
I'M GOING TO REPEAT IT JUST TO
BE SURE WE'RE ALL ON THE SAME
PAGE WHEN DISCUSSING ISSUES
RELATED TO BIOREPOSITORIES AND
OTHER DATA BANKS.
SO AS FAR AS THE LEVERAGING
EXISTING BIOREPOSITORIES, THE
MAIN CHALLENGE IS DO WE HAVE THE
INFRASTRUCTURE TO HANDLE THESE
KIND OF BIOREPOSITORIES AND
LARGE DATA BANKS, AND THE COMMON
THEME ARISES WITH EACH AND EVERY
QUESTION THAT WE DISCUSSED IS,
WHWHERE IS THE FUNDING COMING FM
ALL THIS INFRASTRUCTURE BUILDING
ACTIVITIES.
AND THE SECOND THING IS THE
MATERIAL TRANSFER AGREEMENT.
SO THE INSTITUTION INVOLVED IN
GETTING A SAMPLE OR DATA FROM A
COMMON REPOSITORY, THE LEGAL
ENTITIES TAKE OVER THAT AND IT
IS A TOTALLY DIFFERENT BALL GAME
WHEN IT COMES TO -- THE SCIENCE
IS KIND OF DISAPPEARING IN THAT
POINT AND THEN IT JUST -- THE
OWNERSHIP OF THE DATA, OWNERSHIP
OF THE SAMPLES BECOMES A MAJOR
ISSUE.
AGAIN, COST INVOLVED IN DOING
THAT ALSO IN SOME INSTITUTION IS
MAJOR PROBLEM.
THE OTHER THING ABOUT THE
BIOREPOSITORIES AND DATA
REPOSITORIES, THE COMPATIBILITY
OF SAMPLES IN DATA FROM
DIFFERENT SITES.
ONE WOULD BE AN -- WHAT WILL BE
AN IDEAL DATASET, SAMPLE SET,
WHAT WOULD BE OPTIMUM DATA THAT
YOU NEED TO CONDUCT YOUR
RESEARCH OR WHATEVER THAT YOU
PLAN ON DOING WITH THOSE SAMPLES
BECOMES A MAJOR QUESTION.
SO THAT MEANS A QUALITY
ASSURANCE MECHANISM, QUALITY
CONTROL MECHANISM SHOULD BE IN
PLACE BEFORE WE REQUEST A DATA
OR SAMPLES.
AGAIN, COST ASSOCIATED WITH THAT
QUALITY ASSURANCE MECHANISM.
SO IF YOU LOOK AT THE COST
DRIVING FACTORS, IT IS THE
QUALITY OF SAMPLES, QUALITY OF
DATA, AMOUNT OF INFORMATION
NEEDED THAT IS A QUESTION BY
INVESTIGATOR AND AVAILABILITY OF
THAT INFORMATION.
SO IF YOU HAVE TO GO BACK AND
COLLECT THAT INFORMATION BEFORE
WE CAN USE THOSE SAMPLES OR
DATA, THAT ACTUALLY ADDS MORE
COST TO IT.
SO THE COST BECOMES A MAJOR,
MAJOR DRIVING FACTOR IN MANY OF
THESE DECISION-MAKING.
THE OTHER THING THAT WE
DISCUSSED IS THE -- WHAT NEW
KNOWLEDGE CAN BE GAINED FROM
EXISTING BIOBANK.
SO THE SIMPLE ANSWER IS
KNOWLEDGE TO BE GAINED ARE VAST
AND NEVER-ENDING, SO THAT
QUESTION, THAT'S NOT AN ISSUE.
DO WE HAVE MORE QUESTIONS?
WE HAVE MANY MORE QUESTIONS.
BUT THE KEY THING IS TO IDENTIFY
THE KNOWLEDGE GAPS SO THAT WE
CAN START FILLING THOSE
KNOWLEDGE WITH SAMPLES OR DATA,
AND IDENTIFYING KNOWLEDGE GAPS
AGAIN, HOW DO WE IDENTIFY THOSE
KNOWLEDGE GAPS, THERE'S PLENTY
OF SYSTEMATIC REVIEWS, ANALYSIS
STRATEGIES THAT HAS NOT BEEN
TRANSLATED INTO THE BIOMARKER
FIELD YET, SO THAT MAY BE
ANOTHER MECHANISM THAT THESE
KIND OF WORKSHOPS CAN UNDERTAKE
THAT HELP TO FILL THESE
KNOWLEDGE GAP, IDENTIFY THE
KNOWLEDGE GAP, FILL THE
KNOWLEDGE GAP.
SO MOST OF OUR WORK NOW ARE
DISCOVERY DRIVEN, HOWEVER, NOT
TRANSLATED INTO A CLINICAL
PRACTICE OR A USEFUL DATA THAT
AN INDUSTRY CAN LEVERAGE TO
PRODUCE SOMETHING THAT IS USEFUL
ON BENCH SLIDE.
THAT DOES NOT HAPPEN AGAIN.
FUNDING CAN BE AN ISSUE.
HISTORICALLY, IF YOU LOOK AT 20
YEARS BACK, MAYBE A SINGLE
MARKER WAS IDENTIFIED BY A LAB
AND THERE WAS A KIT OR SOMETHING
USED AND LATER ON WE REALIZE
THAT'S NOT ENOUGH AND IT BECAME
MULTIPLE MARKER TESTS HAVE COME
OUT IN THE FIELD FOR DIFFERENT
INDICATIONS, NOT JUST PREGNANCY,
AND NOWADAYS WE ARE USING
MULTIPLE COMPLEX META --
MULTI-OMICS ANALYSIS, BUT THAT
HASN'T SOLVED THE PROBLEM
EITHER.
HAVE ANY OF THESE TRANSLATED
INTO A CLINICAL PRACTICE?
SO THAT MEANS WE STILL HAVE
KNOWLEDGE GAPS.
SO UNLESS WE START IDENTIFYING
THE KNOWLEDGE GAPS, HAVING THE
BIOREPOSITORIES AND HAVING THE
DATA BANKS MAY NOT BE THAT
USEFUL.
WE ARE STILL LOOKING FOR THINGS
THAT ARE PERSONAL INTEREST THAT
MAYBE WAS A PAPER OR A GRANT,
OPPORTUNITY TO WRITE A GRANT.
WE WILL END UP THERE.
THE OTHER ISSUE THAT WE
IDENTIFIED IN GETTING THE BEST
PRACTICE, CAN WE DEVELOP BEST
PRACTICE FOR FUTURE BIOSAMPLE
COLLECTION.
THERE IS A MAJOR DISCONNECT
BETWEEN AN ACADEMIC INVESTIGATOR
INDUSTRY PARTNER, AND MAYBE THE
END USER WHICH WILL BE A
CLINICIAN.
SO THERE IS -- EVEN IF I'M
STARTING A DISCOVERY RESEARCH IN
AIMING TO FIND THE BIOMARKER FOR
IDENTIFYING -- CONDITION OR A
PROGNOSIS OR DIAGNOSIS OR
WHATEVER IT IS, WHEN IT GOES TO
AN INDUSTRY PARTNER, THEY OFTEN
SAY THIS IS NOT WHAT WE ARE
LOOKING FOR.
AND LET'S SAY IF I CONVINCE AN
INDUSTRY PARTNER AND GO BACK AND
DO THE RESEARCH AND IDENTIFY
SOMETHING, THAT MAY NOT BE THE
ONE THAT IS USEFUL FOR THE
CLINICIAN.
NOW, IF ALL THESE THINGS ARE
SATISFIED, IF IT'S A REGULATORY
AGENCY THEY MAY SAY THIS IS NOT
IDEAL FOR A REGULATORY AGENCY
FOR APPROVAL.
SO I THINK THERE IS A DISCONNECT
BETWEEN ALL THESE AGENCIES,
ACADEMICIAN AND INDUSTRY AND
REGULATORY AGENCY AND THE
CLINICIAN.
SO THERE SHOULD BE A PLATFORM
FOR ALL OF US TO SIT DOWN AND
OPERATE TOGETHER AND DISCUSS
TOGETHER AND IDENTIFY WHAT IS
NEEDED BY EACH GROUP.
AGAIN THIS IS SOMETHING A
WORKSHOP LIKE THIS CAN
POTENTIALLY THINK ABOUT HAVING
SOME OF THE OTHER PARTNERS THAT
CAN BENEFIT THAT, WE WILL
BENEFIT AND UNDERSTANDING EACH
OTHER'S LANGUAGE.
HOW CAN WE PREPARE FOR NEW AND
EMERGING TECHNOLOGIES?
WE TALK ABOUT THE MULTI-OMICS
AND ARTIFICIAL INTELLIGENCE,
MACHINE LEARNING APPROACHES BUT
WHAT IS THE ROLE OF AN ACADEMIC
RESEARCHER IN USING THIS, VERSUS
WHAT IS THE ROLE OF THE
CLINICIAN?
WE'RE ALL TALKING DIFFERENT
LANGUAGES, SO THERE SHOULD BE A
HARMONY BETWEEN THE LANGUAGES
THAT WE ALL SPEAK.
WHEN OUR NEEDS ARE DIFFERENT,
OUR GOALS ARE DIFFERENT, BUT AT
THE SAME TIME, WE HAVE TO FIND A
COMMON PLATFORM OR COMMON THEME
TO OPERATE THAT WE WILL BENEFIT
FROM THESE EXERCISES.
WE ALSO TALKED ABOUT HAVING AN
A.I. OR MACHINE LEARNING CORE
LABS IN INSTITUTES MAY BENEFIT
INVESTIGATORS BECAUSE WE DON'T
HAVE TO DEPEND ON SOMEBODY WE
DON'T KNOW, THEY SEE OUR DATA,
SO HAVING SOMETHING -- AND THESE
CODE LABS, MACHINE LEARNING CODE
LABS, IF THEY ARE IN HARMONY, IF
THEY KNOW WHAT THEY WANT TO DO
TO COME OUT OF ALL THESE
RESEARCH, THAT MAY BENEFIT AS
WELL.
SO I THINK THAT'S PRETTY MUCH
WHAT I HAVE FOR -- THE BOTTOM
LINE IS -- BECOMES A MAJOR ISSUE
NO MAKER IT WHAT WE DISCUSS, HOW
WE DISCUSS.
IMPORTANT DIALOGUE BETWEEN
INDUSTRY AND ACADEMIA,
REGULATORY AGENCIES, FUNDING
AGENCIES, CRITICAL
INFRASTRUCTURE NEEDED TO HAVE
THAT PLATFORM FOR DIALOGUE, ALSO
TO -- FUNDING, SO THAT'S A KEY
LIMITATION.
THAT'S ALL WE HAVE.
>> GREAT.
THANK YOU FOR THAT SUMMARY.
I SEE DAVID TUR TURNED HIS MIC .
>> I WAS ASSIGNED TO BE THE
REPORTER.
WE HAD VERY SIMILAR THEMES TO
WHAT A LOT OF THE OTHER GROUPS
SAID, WE WERE MORE THE A.I./M.L.
SO WE FOCUSED A LOT ON DATA AND
WHAT REALLY THOSE NEEDS ARE.
WE REALLY CAME DOWN TO A LOT
OF -- WE REALLY NEED COMMON DATA
ELEMENTS, THAT THESE DATABASES
HAVE GOT TO HAVE SIMILAR THINGS
THAT CAN BE PUT TOGETHER, AND
REALLY HOW DO WE DO THAT, HOW DO
WE PRIORITIZE IT.
SOME FOLKS HAD TALKED ABOUT THE
NCATS MC3 COVID DATA INTEGRATION
AND HOW SUCCESSFUL THAT WAS AT
REALLY BRINGING THINGS TOGETHER
IN USABLE FORMATS AND HOW CAN WE
POTENTIALLY LEVERAGE THOSE
EXPERIENCES INTO PERINATAL
SPACES.
WE HAD ONE OF THE MEMBERS OF OUR
GROUP THAT SAID IF THEY ARE
LOOKING AT THAT, IT'S A MESS, SO
MORE TO COME HOPEFULLY OF A
LITTLE BIT EASIER.
WE DID TALK ABOUT USING THINGS
FROM THE ELECTRONIC HEALTH
RECORDS, USING OMA PLATFORMS,
REALLY TRYING TO KEEP THOSE AS
STANDARDIZED TO GET THEM
POPULATED MORE.
BUT OMOP CURRENTLY DOESN'T HAVE
A WHOLE LOT OF MATERNAL
VARIABLES SO HE THER THERE'S GRS
TRYING TO WORK ON THAT SO THAT
WOULD BE A POTENTIAL VEHICLE
WITH WHICH TO GET BETTER COMMON
DATA ELEMENTS TOGETHER.
WHEN WE TALKED ABOUT BIOSAMPLES
AND BIOREPOSITORIES, WE ALSO
KIND OF CAME TO THIS
STANDARDIZATION OF HOW SPECIMENS
ARE COLLECTED, HOW THEY'RE
DOCUMENTED, SO THAT THEY CAN BE
ANALYZED AND RETRIEVED THE WAY
THAT WE NEED THEM TO FOR THE
DIFFERENT STUDIES.
AND THEN OUR CONVERSATION SORT
OF MEANDERED CLOSER TO THINGS OF
GOVERNANCE, AND THINGS THAT
WE'VE HEARD BEFORE AND SOME OF
THESE THEMES OF WHO OWNS THE
DATA, WHOSE RESPONSIBILITY FOR
IT -- WHO'S RESPONSIBLE FOR IT,
AND WHO GOVERNS IT, HOW DO
IDENTIFY WHO YOU CAN SHARE IT
WITH, HOW YOU CAN SHARE IT.
THERE WAS A THOUGHT THAT
POTENTIALLY USING BLOCKCHAIN
HERE CAN HELP WITH SOME OF THE
LINKAGES BECAUSE IF YOU LOSE --
IF YOU DE-IDENTIFY EVERYTHING
AND THEN HOW DO YOU -- BUT YOUR
SPECIMENS ARE IDENTIFIED BY
MEDICAL RECORD NUMBERS, HOW DO
YOU GET ALL OF THOSE THINGS
TOGETHER.
THE GA4GH GROUP OF TACKLING
THESE KINDS OF PROBLEMS WAS
BROUGHT UP, AND IT WAS SORT OF A
THOUGHT THAT A LOT OF THIS HAS
TO BE GENERATED ABOVE US.
THERE'S SOMEONE WHO HAS LEVERAGE
TO MAKE SURE THAT THESE THINGS
GET IMPLEMENTED ACTUALLY HAS TO
BE HELPING OUT IN TERMS OF
DETERMINING THESE COMMON
ELEMENTS, AND THAT LED US INTO A
DISCUSSION OF STAKEHOLDERS AND
SOME OF THAT CAME OUT IN THE
OTHER GROUPS AS WELL, BUT THE
STAKEHOLDERS, WHEN IT COMES TO
THE DATA, YOU HAVE TO LOOK AT
WHAT THE MOTIVATIONS ARE BECAUSE
THE HEALTH SYSTEMS' MOTIVATIONS
ARE VERY DIFFERENT THAN US AS
RESEARCHERS AND IS VERY
DIFFERENT THAN THE CLINICIANS
OUT IN RURAL AMERICA.
AND SO YOU HAVE TO BRING ALL OF
THESE STAKEHOLDERS TOGETHER TO
TRY TO FIGURE OUT HOW YOU CAN
REALIZE WHAT EVERYBODY NEEDS OUT
OF THIS NEW SCENARIO THAT
BECOMES AVAILABLE FOR THEM, AND
YOU HAVE TO GET THE MEDICAL
RECORD COMPANIES INVOLVED
BECAUSE THEY HAVE A DIFFERENT
SET OF PRIORITIES AS WELL, BUT
WE REALIZE THAT IN ORDER TO GET
ALL OF THESE PEOPLE WHO HAVE
DIFFERENT DRIVERS, WE REALLY
NEED SOME TOP-DOWN PEOPLE WITH
LEVERAGE AND WE THOUGHT THE NIH
OR IN SOME KIND OF UNIVERSAL
HEALTH SYSTEM COMES ABOUT IN THE
NEXT 25 DAYS OR SOMETHING, YOU
KNOW, WHICH WOULD BE NICE, YOU
KNOW, IF WE CAN MAKE SOME KIND
OF REVOLUTIONARY CHANGE LIKE
THAT, THAT WOULD ALLOW FOR SOME
LEVERAGE THAT IF YOU WANT THIS,
IF YOU WANT THIS MONEY, IF YOU
WANT THIS GRANT FUNDING TO DO
THESE RESEARCH, YOU HAVE TO HAVE
THESE THINGS PUT IN PLACE FOR
COMMON ELEMENTS.
AND THAT REALLY IS THE FIRST
PLACE TO START, IS GETTING ALL
OF THESE COMMON THINGS TOGETHER,
AND FIGURING OUT THE COMMUNITY
OF STAKEHOLDERS WITH WHICH TO
MAKE THESE CHANGES IS SOMETHING
THAT IS REALLY IMPORTANT BECAUSE
IF YOU DON'T HAVE ALL THE
STAKEHOLDERS, WE TALK ABOUT THE
RESEARCH COMMUNITY CAN COME UP
WITH ALL THIS STUFF AND WE CAN
HAVE ALL THESE A.I.-GENERATED
MODELS AND ALL THESE THINGS THAT
SAY IT'S GREAT, BUT THAT'S NOT
THE MAJORITY OF PEOPLE WHO ARE
TAKING CARE OF PATIENTS.
AND WHO MAY BE ORDERING THESE
TESTS.
LOUIS BROUGHT UP A GOOD POINT,
WE WENT FROM A FOUR-PAGE
ACOG-DRIVEN PAPER CHART THAT WAS
ALL OF PREGNANCY IN FOUR PIECES
OF PAPER, AND NOW WE'VE GOT
THESE COMPUTER SYSTEMS WITH
25,000 PAPERS IF YOU PRINT OUT A
RECORD FROM A PREGNANCY, AND
PEOPLE ARE JUST TYPING IN,
CUTTING AND PASTING IN ALL OF
THEIR NOTES.
SO YOU CAN'T GET THE DATA UNLESS
YOU GET ALL OF THOSE
STAKEHOLDERS INVOLVED AND THAT
THEY'RE GOING TO IMPLEMENT IT.
SO THAT WAS SORT OF WHERE WE
LANDED.
>> ALL RIGHT.
SO WE'RE ACTUALLY DOING PRETTY
GOOD ON TIME, SO I THINK I WOULD
LIKE TO OPEN IT UP TO ANY
QUESTIONS THAT PEOPLE HAVE OR
ANY COMMENTS, AND I KNOW THERE
WAS ONE, I CAN'T SEE YOUR TENT
CARD BUT -- FEEL FREE TO ASK THE
FIRST QUESTION.
>> SO IN TERMS OF THE GROUP
ONE'S COMMENTS ABOUT INCREASING
DIVERSITY BY USING DOCUMENTS
TRANSLATED INTO APPROPRIATE
LANGUAGES, I DO THINK THAT --
MAYBE I THINK MAYBE ABOVE NICHD,
BUT FOR EXAMPLE, THE PHOENIX
TOOLKIT IS A SET OF INSTRUMENTS
THAT ARE USED PRETTY WIDELY, I
THINK, FOR COLLECTING DIFFERENT
TYPES OF INFORMATION, SDOH, DEM
GRAPHICS, LOTS OF THINGS LIKE
THAT, VERY FEW OF THOSE
INSTRUMENTS ARE AVAILABLE IN
SPANISH.
I AM SURE THAT EACH OF THOSE
INSTRUMENTS HAS BEEN TRANSLATED
MULTIPLE TIMES BY MULTIPLE
NIH-FUNDED INVESTIGATORS, SO
HAVING THEM AVAILABLE FROM THE
GET-GO WOULD SAVE A LOT OF TIME.
WE'RE REDOING IT NOW FOR THE
MULTI-OMICS CONSORTIUM, BECAUSE
ONLY TWO OUT OF I THINK 10 THAT
WE'RE GOING TO USE ARE
TRANSLATED.
SO THAT WAS MY -- I GUESS A
COMMENT MORE THAN ANYTHING.
AND WE'D BE HAPPY TO SHARE THE
TRANSLATED VERSION.
>> ANY OTHER QUESTIONS OR
COMMENTS FOR THE FULL GROUP?
ALL RIGHT.
I AM NOT SEEING ANY.
I'LL JUST -- I'LL JUST KIND OF
SUM UP A LITTLE BIT MY THOUGHTS.
I MEAN, THIS HAS BEEN A REALLY
FANTASTIC DAY IN TERMS OF THESE
SESSIONS AND REALLY, I THINK,
SURFACING A LOT OF THINGS WE'RE
GOING TO NEED TO IT CONTINUE
TALKING ABOUT.
I KNOW I SORT OF STARTED MEETING
WITH THAT BUT IT WAS REALLY SOME
OF THE COMMENTS THAT CAME UP
FROM THE GROUP LEADERS THAT IS
SORT OF MAKING ME THINK ABOUT A
VENUE OR A WAY WHERE ALL THESE
STAKEHOLDERS CAN HAVE CONTINUED
DISCUSSION.
I THINK THAT MIGHT BE SORT OF
MY -- AT LEAST RIGHT NOW, THE
BIGGEST TAKEAWAY THAT I HAVE,
BECAUSE I THINK A LOT OF WHAT
WE'RE TALKING ABOUT ISN'T GOING
TO BE FIGURED OUT IN A WORKSHOP
EVERY SIX MONTHS OR A YEAR, AND
CERTAINLY A PLACE WHERE MANY
STAKEHOLDERS CAN COME IN FROM
THE FEDERAL GOVERNMENT, PRIVATE
SECTOR, ACADEMICS, STARTUPS,
ENTREPRENEURS, VENTURE
PHILANTHROPY, ET CETERA, SO
THAT'S SORT OF MY ONE BIG
TAKEAWAY.
SO AGAIN, THANKS TO EVERYBODY
FOR THIS, AND I WILL TURN TO
ZHAOXIA FOR SOME CLOSING REMARKS
AND SOME FUTURE PLANS.
>> THANK YOU, AARON.
SO WHILE IT IS A INCREDIBLE DAY,
A VERY EXCITING AND VERY
ENLIGHTENING WHOLE DAY AND WITH
A LOT OF, YOU KNOW, MANY, MANY
PRESENTATIONS, VERY STIMULATING
DISCUSSIONS AND COMMENT,
VARIABLE COMMENTS, AND AS AARON
JUST MENTIONED THAT A LOT OF
VARIABLE COMMENTS/SUGGESTIONS OR
TAKE-HOME MESSAGES, WE NEEDED TO
THINK ABOUT AND CONTINUE -- OUR
ORIGINAL PLAN HAD ALREADY
THOUGHT ABOUT MAYBE WE WILL HAVE
FOR THE FUTURE WE'LL HAVE A
SERIES OF CONFERENCES,
DEFINITELY THIS HAS LAID OUT A
FOUNDATION FOR US TO CONTINUE
THINKING, MAYBE IN THE FUTURE,
WE WILL PLAN ON HAVING
CONFERENCES FOCUSING ON SPECIFIC
TOPICS THAT CAME UP FROM TODAY'S
WORKSHOP.
OF COURSE THIS IS A VERY SHORT
MEETING, JUST ONE DAY, ON VERY,
VERY IMPORTANT TOPICS WHICH WE
COULD EXTEND SOME OF THE TOPICS
FOR A WHOLE DAY OR TWO DAYS.
SO WE DIDN'T HAVE TIME TO GET
INTO THAT.
SO THAT IS ACTUALLY ON OUR
THINKING AND OUR PLAN FOR FUTURE
EVENT.
SO WITH THAT, I WOULD LIKE TO
EXPRESS MY HEARTFELT
APPRECIATION FOR ALL THE
PARTICIPANTS TO THE SPEAKERS, TO
THE MODERATORS AND THE GREAT
GROUP CHAIRS AND CO-CHAIRS FOR
YOUR COMMITMENT, YOUR HELP AN
AND -- YES, AND SO REALLY
WITHOUT YOU THIS WOULD NOT BE
POSSIBLE, AND SO THIS IS A VERY,
VERY, VERY HELPFUL -- WE REALLY
APPRECIATE IT.
ALSO WE'D LIKE TO THANK THE
LOGISTICS TEAM AND ALSO THE NIH
EVENT MANAGEMENT STAFF.
THEY ARE WORKING BEHIND THE
SCENES AND WITHOUT THEM, THIS
WORKSHOP WOULD NOT BE POSSIBLE
AS WELL.
AND THANK YOU ALL AGAIN AS WE
STAY CONNECTED AS WE CONTINUE TO
THINK ABOUT THE CURRENT APPROACH
OR EVEN COME UP WITH A NOVEL
APPROACH BY LEVERAGING EXISTING
RESOURCES AND INTEGRATE CUTTING
EDGY MERGING TECHNOLOGIES AND
A.I. IS A HOT, HOT TOPIC, FOR
THE DAY I THINK IT WOULD BE
CONTINUED FOR MANY YEARS.
SO LET US STAY CONNECTED SO WE
WILL CONTINUE TO TACKLE THE VERY
IMPORTANT QUESTION AND ISSUE
RELATED TO MATERNAL HEALTH
OUTCOMES, HOPE THAT THIS EFFORT
WILL MOVE THIS FIELD FORWARD.
SO THANK YOU AGAIN, AND ALL HAVE
A SAFE TRIP HOME.