GOOD MORNING, EVERYBODY.
PETER TARCZY-HORNOCH AND THIS
MEETING IS NOW CALLED TO ORDER.
THIS PART OF THE MEETING IS
BEING BROADCAST LIVE ON THE NIH
VIDEOCAST SIDE AND RECORDED FOR
ON DEMAND VIEWING.
I'D LIKE IT THANK THE MEMBERS OF
THE BOARD OF SCIENTIFIC
COUNSELORS AND THE NLM FACULTY
AND STAFF FOR THEIR SUPPORT AND
WOULD ALSO LIKE TO ANNOUNCE FOR
THIS SESSION AND THE NEXT ONE
JORDAN WILL BE CO-CHAIRING THE
INCOMING CHAIR AND I'LL BE
TRANSITIONING OFF AFTER THE NEXT
BOARD OF SCIENTIFIC COUNSELORS
MEETING AND WOULD LIKE TO THANK
JEAN FOR TAKING THE REINS OF
THIS ILLUSTRIOUS GROUP.
WITH THAT I RECOMMEND WE GO
AHEAD AND PROCEED WITH OUR
REMARKS FROM STEVE SHERRY THE
ACTING NLM DIRECTOR AND THEN
RICHARD SCHEUERMANN.
>> GREAT, THANK YOU, PETER.
HOLD ON I'M SETTING UP TO SHARE
HERE.
HERE WE GO.
ALL RIGHT, WELCOME AND GOOD
MORNING EVERYONE.
I'M EXCITED TO SHARE THE LATEST
UPDATE I'M STEVEN SHERRY THE
ACTING DIRECTOR OF THE NATIONAL
LIBRARY OF MEDICINE.
BEFORE I GET STARTED I'D LIKE TO
ACKNOWLEDGE THE DEDICATED
LEADERSHIP TEAM, THESE ARE OUR
SENIOR LEADERS DRIVING OUR
SUCCESS AT NLM AND PROUD TO WORK
AMONGST THIS INCREDIBLE GROUP OF
LEADERS.
I HAVE TRANSITION NEWS TO START.
FIRST I'M EXCITED TO ANNOUNCE
DR. FUNG WAS APPOINTED THE
DIRECTOR OF THE LISTER HILL
LHNCBC AND HAS BEEN WITH US 20
YEARS AND PUBLISHED RESEARCH ON
COVID-19, LONG COVID, HIV AND
OTHER TOPICS.
I'M ALSO PLEASED TO ANNOUNCE JIM
MORK HAS BEEN NAMED THE DEPUTY
DIRECTOR OF LISTER HILL
COMMUNICATION.
HE SERVED AS THE CDC'S ACTING
DIRECTOR AND BRINGS MORE THAN 26
YEARS OF EXPERIENCE IN
BIOMEDICAL RESEARCH AND PRODUCT
ASSESSMENT AND NATURAL LANGUAGE
PROCESSING TO HIS NEW ROLE.
WE'RE HAPPY TO HAVE THEM IN
THEIR NEW ROLES.
AND THE NLM INTERMURAL DIVISION
THE BRANCH WAS PREVIOUSLY HOUSED
UNDER THE COMPUTATIONAL BIOLOGY
BRANCH UNDER BIO TECHNOLOGY AND
INFORMATION.
IN THIS UPDATED CHART THE
REORGANIZATION HAS ESTABLISHED
THE DIR AS A SEPARATE NLM
DIVISION THAT WILL NOW CONTAIN
THE COMPUTATIONAL HEALTH BRANCH
AND COMPUTATIONAL BIOLOGY BRANCH
AS WELL AS ITS OWN OFFICE OF THE
DIRECTOR.
THE MILESTONE REPRESENTS A
POSITIVE INVESTMENT IN GROWING A
CENTER OF EXCELLENCE FOR
INNOVATION AND COMPUTATIONAL
BIOLOGY AND HEALTH INFORMATICS
RESEARCH.
IN THE NEW DIR, INVESTIGATORS
WILL CONTINUE TO EXPAND THEIR
DIVERSE COLLABORATIVE COMMUNITY
TO ADVANCE KNOWLEDGE AND IMPROVE
HUMAN HEALTH.
I'D LIKE TO POINT OUT RICHARD
SCHEUERMANN CONTINUES TO SERVE
AS THE SCIENTIFIC DIRECTOR AND
RESPONSIBLE FOR THE OVER ALL
DIRECTION AND QUALITY CONDUCTED
BY THE DIR.
DAVID LANCEMAN IS CHIEF OF THE
COMPUTATIONAL BIOLOGY BRANCH AND
ACTING CHIEF OF THE
COMPUTATIONAL HEALTH RESEARCH
BRANCH.
NOW FOR UPDATES ABOUT NLM'S
COMMITMENT TO INNOVATION.
THERE'S FOUR DISTINCT WORK
STREAMS TO BUILD THE PROGRAM.
THEY'RE GOVERNANCE AND
MANAGEMENT, DEPLOYMENT AND
MEASUREMENT AND LIFE CYCLE AND
ORGANIZATIONAL READINESS.
ALL WORK STREAMS HAVE ACHIEVED
THEIR OUTCOMES AND THE PROGRAM
OFFICIALLY LAUNCHED SEPTEMBER
26.
THE NLM PROGRAM WILL EMPOWER
STAFF TO SUBMIT NOVEL IDEAS FOR
ADDRESSING DIFFICULT PROBLEMS OR
SEIZING NEW OPPORTUNITIES, ALLOW
STAFF TO SHOWCASE THEIR
SOLUTIONS ACROSS THE NLM AND
ASSIST STAFF IN MAKING A MARK
HOW IT CONTRIBUTE TO THE NLM'S
MISSION.
FOR THE PROGRAM, WE RECENTLY
SELECTED OUR FIRST INNOVATION
PROGRAM FACILITATOR COHORT.
WE HAVE INITIALLY TARGETED
HAVING TWO INNOVATION PROGRAM
FACILITATORS AND GIVEN THE LEVEL
OF INTEREST ACROSS NLM STAFF WE
INCREASED IT TO SIX.
AS OF OCTOBER 17, WE ALREADY
RECEIVED FIVE INNOVATION IDEA
SUBMISSIONS AND HAVE NEARLY 20
ADDITIONAL DRAFT SUBMISSIONS IN
THE QUEUE.
THESE ARE GOING THROUGH THE
INITIAL EVALUATION PROFESSION
AND WILL BE REVIEWED BY OUR
INNOVATION PROGRAM BOARD SOON.
THE PROGRAM REPRESENTS OUR
COMMITMENT TO PRIORITIZING
PURSUIT TO MEET THE DIRECTOR'S
VISION AND NLM COMMUNITY.
NOW AN UPDATE ON IS THE BUDGET.
THE FISCAL '25 PRESIDENT'S
BUDGET HAS A PROGRAM LEVEL OF
$50.1 MILLION AND THE REQUEST IS
$28.8 MILLION.
ONGOING BUDGETS HAVE NOT BEEN
COMPLETED AND WE'RE STILL
OPERATING UNDER A CONTINUING
RESOLUTION LASTING THROUGH
DECEMBER 20.
I'D LIKE TO PIVOT FOR EXCITING
ACCOMPLISHMENTS FROM NLM'S
DIVISIONS AND PROGRAMS.
FIRST, I'M EXCITED TO SHARE AN
UPDATE ABOUT THE MODERATE
ELECTRONIC DATA FOR INDIVIDUALS
KNOWN AS FEHRDI.
WE ANNOUNCED THE LAUNCH OF THE
DATA INCLUDING PERSONALLY
IDENTIFIABLE INFORMATION AND
UNDER PIN INITIATIVES AND IT'S
EXTENDED TO INCLUDE 11 DATA
SETS.
I'M ALSO HAPPY TO SHARE AN
UPDATE ON THE CCOI.
IT'S AN EVOLVING PROJECT THAT
SEEKING TO LOWER BARRIERS TO
FINDING AND USING LARGE CLINICAL
DATA SETS.
LISTER HILL CENTER LAUNCHED IT
IN MAY.
THE WEBSITE SUPPORTS THE MISSION
BY PROVIDING THE PUBLIC BY DATA
SET PROFILES.
PROFILES INCLUDE THE METADATA
AND COMPRISED OF AN OVERVIEW
BASIC STATISTIC AND CONCEPT
COUNTS FOR EACH CLINICAL DATA
SET.
NLM HOSTS FOUR DATA SETS
FEATURED ON THE WEBSITE.
I'M ALSO PLEASED TO RECAP
ADVANCEMENTS IN BIO INFORMATICS
AND THE NLM MALARIA SCREENER
PROJECT IS A COLLABORATION TO
THE EFFICACY OF MALARIAL DRUGS
WITH MACHINE LEARNING AND
ENABLING LABS TO HAVE THE
ENHANCED CAPABILITY TO ANALYZE
CANDIDATES AROUND THERE'S
COLLABORATIONS BETWEEN THE
LISTER HILL CENTER AND THE
COLLECTION DIVISION KNOWN AS
USCD ANDING OFF OF COMPUTER AND
COMMUNETATION SYSTEMS.
THIS COLLABORATION IS THE
INTELLIGENT EDITING ASSISTANCE
HELPING EDITORS FIND MATCHES
AMONG 3 MILLION CONCEPTS FOR THE
NEARLY 100,000 NEW TERMS ADDED
EVERY SIX MONTHS.
AND THIS IS DONE BY APPLYING
DEEP LEARNING TECHNIQUES TO
SUPPORT QUICK INDEXING CURATION
AND CONCEPT MATCHING.
I'M ALSO PLEASED TO SHARE PUB
MED CENTRAL REACHED THE 01
MILLION ARTICLE MILESTONE WITH 7
MILLION ARTICLES ADDED SINCE
2014 AND 6 MILLION OPEN ACCESS
ARTICLES NOW AVAILABLE FOR
MACHINE LEARNING AND OTHER REUSE
UNDER THE LICENSE TERMS OF
PARTICULAR ARTICLES.
PMC BEGAN UPDATING THE
TECHNOLOGY FOR USABILITY AND
SUSTAINABILITY AND THE FEATURES
HAVE BEEN AVAILABLE FOR PREVIEW
SINCE MARCH FOR TESTING AND
FEEDBACK AND THEY TRANSITIONED
TO RUN ON CLOUD SERVICES.
THE NEW SITE UPDATES ALSO
INCLUDE AN UPDATED LOOK AND FEEL
FOR ARTICLES THAT ARE FOCUSSED
ON IMPROVING ACCESSIBILITY AND
READABILITY OF THE CONTENT,
IMPROVED ARTICLE NAVIGATION AND
ADDING A NEW JOURNAL LIST
DISPLAY.
THE TEAM INCORPORATED
ACCESSIBILITY INTO THE
DEVELOPMENT INCLUDING FEATURE
PRIORITIZATION AND TESTING.
AND THE UPDATED DESIGN USES
U.S. WEB DESIGN SYSTEM
COMPONENTS AND DESIGN PRINCIPLES
TO HELP IMPROVE THE READABILITY
AND ACCESSIBILITY OF ARTICLE
PAGES AS SHOWN ON THE LEFT.
THE PMC TEAM WILL CONTINUE TO
WORKING TOWARDS AN ACCESSIBLE
AND CONSISTENT USER EXPERIENCE
REGARDLESS OF WHETHER THE USER
IS VISITING PMC ON A DESK TOP,
MOBILE DEVICE OR INCREASINGLY
ASSISTIVE TECHNOLOGY.
ACHIEVING OUR OPEN SCIENCE
ASPIRATIONS REQUIRES ADVANCING
DIGITAL ACCESSIBILITY ACROSS
RESOURCES AS WE'VE DONE AT PBNC.
NOW THE COMPARATIVE GENOMIC
RESOURCE.
IT HAS ANALYSIS TOOLS FOR THE
STUDY OF EUKARYOTIC ORGANISMS
WITH DATABASES AND THE NCBI DATA
SPENTS BLAST, WHICH IS NLM'S
PLAYINGSHIP RESOURCE FOR
SEQUENCED SEARCHS CHANGES THE
NUCLEOTIDE DATABASE TO AN
EFFICIENT COLLECTION OF
SEQUENCES THAN THE PREVIOUS NR.
NCBI DATA SETS NOW PUBLISHED IN
SCIENTIFIC AND NATURE AND
SCIENTIFIC DATA MODERNIZE HOW
GENOME TAX ONOMY IS DOWNLOADED
FROM THE WEB.
NCBI DATA SETS REPLACES THE
LEGACY GENOME AND ASSEMBLY
RESOURCES.
THESE WERE RETIRED ON JULY 15
AND DATA SETS PROVIDE A SINGLE
ENTRY POINT TO GENE-RELATED DATA
NCBI.
HOWEVER, THERE NOT CHANGE TO HOW
USERS PROGRAMMATICALLY ACCESS
AND WE MODERNIZED OUR APPROACH
TO CONTINUE TO BE AN EXEMPLAR OF
A DATA CENTER REPRESENTING 23
SYSTEMS.
THE SYSTEM REALIGNMENT RESULTED
IN AUTHORIZATION BOUNDARIES.
EACH DIVISION WITHIN NLM IS
RESPONSIBLE FOR THE TECHNICAL,
OPERATIONAL AND MANAGEMENT
CONTROLS THAT ARE NECESSARY TO
SAFEGUARD THEIR INFORMATION AND
SYSTEM AND SUPPORTING THEIR
SERVICES AND BUSINESS
OPERATIONS.
THESE THREE NEW REPORTED SYSTEMS
ALIGN MORE CLOSELY WITH OUR
DIVISION'S SPECIFIC
AUTHORIZATION BOUNDARIES.
THIS BETTER MEETS THE SECURITY
COMPLIANCE REQUIREMENTS.
IN JANUARY WE LAUNCHED THE DATA
SET CATALOG.
IT'S A DISCOVERY TOOL CALLED THE
DATA SET METADATA MODEL OR DATMM
TO PROVIDE A COMMON DATA MODEL
FOR DESCRIBING DATA SETS IN
REPOSITORIES.
IT WILL BE AN ESSENTIAL
FRAMEWORK FOR DOING DISTRIBUTED
OR DATA SYSTEM CATALOGING
RESEARCH SETS ACROSS THE
INTERNET AND BETWEEN NLM AND OUR
COLLABORATING REPOSITORIES.
WE CURRENTLY HAVE SEVEN
REPOSITORIES IN THE DATA SET
CATALOG INCLUDING DB GAP,
IMPORT, DRIAD.
IN 2025 THE CATALOG TO ADD MORE
AND IMPLEMENT ENHANCEMENTS AND
UPGRADE THE ENVIRONMENT AND
REDUCE LOADING TIME AND
FRAMEWORK FOR EXPANSION.
NOW NEWS FROM THE NLM DIGITAL
COLLECTION.
FIVE NEW DIGITIZED ARCHIVAL
COLLECTIONS ARE LISTED HERE AND
AVAILABLE AND TWO DIGITIZED IN
COLLABORATION WITH ADAM MATTHEW
PUBLISHING AND TWO CIVIL WAR
COLLECTIONS AND OVER 26,000
PAGES FROM THE BACTERIOLOGIST
WHO CONTRIBUTED TO THE 1964
SURGEON GENERAL'S REPORT ON
SMOKING AND HEALTH.
NLM IS MAKING THEM AVAILABLE IN
A DIGITAL FORM TO ALL
DISCIPLINE.
AND I'M EXCITED TO ANNOUNCE
NLM'S ENVIRONMENT EXHIBITION
THIS LEAD IS KILLING US, A
HISTORY OF CITIZENS FIGHTING
LEAD POISONING RECEIVED AN
AAWARD FROM HIAA AND EXHIBITS
PAST ERTS TO PREVENT LEAD
EXPOSURE AND FROM DUMPING AND
LED PIPES.
THROUGH THE AWEIRD -- AWARD IT
SEEKS OTHER VIRTUAL EXHIBITS AND
IT WORKED WITH THE OFFICE KNOWN
OR ORWH FOR WOMEN'S HEALTH
RESEARCH.
THE NEW PRODUCT IS CALLED
DISCOVERY WHR AND PUBLICALLY
LAUNCHED IN SEPTEMBER.
IT FACILITATE THE DISCOVERY OF
RESEARCH ON LITERATURE ON HEALTH
ISSUES PRIMARILY AFFECTING WOMEN
SUCH AS MENOPAUSE AND POLY
CYSTIC OVARY SYNDROME AND AUTO
IMMUNE DISORDERS AND RESEARCHERS
AND THE PUBLIC ARE ABLE TO
EASILY DISCOVER THE LATEST
FINDINGS AND ONGOING RESEARCH
ACTIVITIES INCLUDING NIH
FUNDING, LITERATURE AND
INFORMATION ON RELEVANT TOPICS
THAT AFFECT WOMEN'S HEALTH.
INITIALLY, THE MVP FEATURES A
FEW SELECT TOPICS WITH MORE TO
COME IN THE MONTHS AND YEARS.
I'D LIKE TO THANK YOU FOR YOUR
TIME TODAY AND NOW I'LL HAND THE
DISCUSSION BACK TO RICHARD
SCHEUERMANN.
THANK YOU.
>> THANKS, STEVE.
ALL RIGHT.
WELL, LET ME START BY THANKING
THE MEMBERS OF THE BOARD OF
SCIENTIFIC COUNSELORS.
I KNOW IT TAKES A FAIR AMOUNT OF
TIME AND EFFORT TO REVIEW OUR
RESEARCH BUT I CAN TELL YOU THAT
WE ALL REALLY APPRECIATE THE
FEEDBACK AND RECOMMENDATIONS WE
GET THROUGH THIS PROCESS
INCLUDING ALL OF OUR
INVESTIGATORS AND SO I REALLY
WANT TO EXPRESS MY APPRECIATION
FOR THE WORK THAT YOU DO FOR THE
NATIONAL LIBRARY OF MEDICINE.
SO, JUST TO REMIND PEOPLE THAT
IN APRIL, YOU ALL REVIEWED TWO
OF OUR INVESTIGATORS DINA
DEMNER-FUSHMAN AND DR. LU AND
PROMOTE TO INVESTIGATOR FOR
TENURE.
WE'RE IN THE PRFLGS OF PULLING
THAT TOGETHER AND PREPARING TO
SUBMIT THAT TO THE NIH TENURE
COMMITTEE HOPEFULLY BY THE END
OF THIS CALENDAR YEAR.
SO THANK YOU FOR THE
RECOMMENDATIONS.
TODAY, YOU'LL BE REVIEWING TWO
OF OUR SENIOR INVESTIGATORS,
TERESA PRZKTYCK AND EUGENE
KOONIN AND HAVE THE MEETINGS SET
FOR MAY AROUND OCTOBER OF 2025
AND LIST THE INVESTIGATORS UP
FOR REVIEW AT THOSE UPCOMING
MEETINGS.
STEVE ALREADY KIND OF NICELY
SUMMARIZED THIS RECENT
RE-ORGANIZATION WE COMPLETED.
WE WERE PREVIOUSLY KNOWN AS THE
INTRAMURAL RESEARCH PROGRAM WITH
WHO HOUSES HOUSED IN TWO
DIVISIONS WIN NLM.
AS A RESULT OF A BLUE RIBBON
PANEL RECOMMENDATION FROM 2018,
THE PANEL RECOMMENDED WE BRING
THE TWO RESEARCH BRANCHS
TOGETHER UNDER A SINGLE
UMBRELLA.
AND I'M HAPPY TO ANNOUNCE THAT
THAT PROCESS HAS BEEN COMPLETED.
WE'RE NOW KNOWN AS THE DIVISION
OF INTRAMURAL RESEARCH AT THE
NATIONAL LIBRARY OF MEDICINE.
AND WE HAVE RECEIVED OFFICIAL
APPROVAL FROM NIH IN SEPTEMBER
OF THIS YEAR.
ON THE RIGHT-HAND SIDE YOU CAN
SEE THE NEW ORGANIZATIONAL
STRUCTURE WHERE OUR DIVISION IS
WIN OF THE FIVE MAIN DIVISIONS
WITHIN NLM AND INCLUDES AN
OFFICE OF THE DIRECTOR AND THEN
THESE TWO RESEARCH BRANCHES, THE
COMPUTATIONAL HEALTH RESEARCH
BRANCH AND THE COMPUTATIONAL
BIOLOGY BRANCH.
SO THAT PROCESS HAS BEEN
COMPLETED.
JUST TO GIVE YOU A BRIEF SUMMARY
OF THE OVER ALL RESEARCH
PRODUCTIVITY OF OUR DIVISION.
WE COMPLIED A LIST OF THE
PUBLICATIONS THAT WE'VE
PUBLISHED IN THE LAST MONTHS
INCLUDING PRIMARY PAPERS AND
REVIEW ARTICLES AND PEER REVIEW
JOURNALS AND PRE-PRINT SERVERS.
THERE'S 189 OF PAPERS THAT OUR
INVESTIGATORS HAVE PUBLISHED IN
THE LAST 12 MONTHS AND I JUST
PUT TOGETHER A LIST OF SOME OF
THE JOURNALS THAT THE PAPERS
WERE PUBLISHED IN AND YOU CAN
SEE THAT OUR INVESTIGATORS ARE
PUBLISHING IN TOP TIER JOURNALS
BOTH GENERAL JOURNALS LIKE PANS
AND NATURE COMMUNICATIONS AND
MORE SPECIFIC INFORMATIC RELATE
JOURNALS AND BIO INFORMATICS AND
JOURNAL OF COMPUTATIONAL BIOLOGY
AND PLOS AT CONTINUE TO BE
PRODUCTIVE.
WE RECEIVED ACKNOWLEDGEMENTS
THROUGH AWARDS AND HONORS AND
THE TWO INVESTIGATORS YOU'LL BE
REVIEWING TODAY WERE RECENTLY
AWARDED THESE OR RECEIVED THE
AWARDS.
EUGENE KOONIN WAS SELECTED AS A
FELLOW OF THE SOCIETY OF
COMPUTATIONAL BIOLOGY EARLIER
AND TERESA RECEIVE THE FRANKLIN
SPECIAL AWARD IN SCIENCE FOR ONE
OF HER RECENT PUBLICATIONS IN
THE JOURNAL OF COMPUTATIONAL
BIOLOGY.
SO IT'S NICE TO HAVE THE
EXTERNAL RECOGNITION OF THE WORK
OUR INVESTIGATORS ARE DOING.
WE ARE IN THE PROCESS OF
EXPANDING OUR GROUP OF ADVOC
ADVOCAADVOCATE
INVESTIGATORS AND COMPLETED A
RECRUITMENT OF A NEW
INVESTIGATORS IN EXPANDING OUR
POOL OF INVESTIGATORS WE'RE
TAKING A TWO PRONG STRATEGY AND
IDENTIFIED KEY RESEARCH AREAS WE
WANT TO EXPAND INTO IN OUR
DIVISION.
AND WE'RE ALSO TAKING AN
OPPORTUNISTIC PERSPECTIVE WHERE
WE LOOK AT SEMIFINAL EFFORTS
THROUGH THE STADTMAN PROGRAM TO
IDENTIFY INVESTIGATORS COMING
THROUGH THE PROGRAM WHO MAY BE A
GOOD FIT FOR THE NLM DIVISION OF
RESEARCH.
IN TERMS OF THE STRATEGIC
APPROACH, WE IDENTIFIED THAT WE
WANTED TO BRING IN SPECIALIZED
EXPERTISE IN THE APPLICATION AND
DEVELOPMENT OF COMPUTATIONAL,
STATISTICAL AND A.I. METHODS
FOCUSSED ON SINGLE CELL
PHENOTYPING AND SPATIAL
TRANSCRIPTOMICS AND SINGLE CELL
EPIGONE EM -- EPIGENOMICS AND
FOUR APPLICANTS WERE SELECTED AS
FINALISTS AND WE HAD IN-PERSON
INTERVIEWS FOR ALL FOUR
FINALISTS COMPLETED IN SEPTEMBER
AND AS A RESULT OF THAT, THOSE
INTERVIEWS WE MADE AN OFFER TO
ONE OF THOSE INDIVIDUALS,
DR. YUN ZANG AND SHE'S AGREED TO
JOIN US IN THE BEGINNING OF
DECEMBER.
SO WE'RE VERY EXCITED ABOUT THIS
NEW ADDITION TO OUR TENURE TRACK
INVESTIGATOR GROUP AND WE'LL
HAVE A CHANCE TO MEET HER IN ONE
OF THE BOARD OF SCIENTIFIC
COUNSELOR MEETINGS.
ON DECK WE HAVE THE
COMPUTATIONAL RESEARCH BRANCH
AND THE COMPUTATIONAL BIOLOGY
BRANCH.
DAVID LANDSMAN HAS BEEN THE CBB
BRANCH CHIEF AND SERVING AS THE
ACTING BRANCH CHIEF FOR CHRB SO
WE'RE KEEN ON FINDING AND
RECRUITING A NEW BRANCH CHIEF
FOR CHRB SO THAT PROCESS WE'RE
IN THE MIDDLE OF PULLING THOSE
MATERIALS TOGETHER, PUTTING
TOGETHER A POSITION DESCRIPTION
AND WE ARE IN THE PROCESS OF
SUBMITTING THAT INFORMATION TO
NIH FOR APPROVAL TO RECRUIT A
NEW BRANCH CHIEF.
SO WE WILL KEEP YOU POSTED ON
THE PROGRESS THAT WE'RE MAKING
THERE BUT I THINK ONCE WE HAVE
APPROVAL AND HAVE THE
INFORMATION AVAILABLE WE ARE
PLANNING ON SHARING THAT WITH
THE BOARD IN CASE YOU KNOW OF
ANY STRONG CANDIDATES THAT MIGHT
BE APPROPRIATE FOR THAT
PARTICULAR POSITION.
AND FINALLY I WANTED TO TELL YOU
A LITTLE BIT ABOUT THE WORK THAT
WE'VE BEEN DOING TO ASSEMBLE A
ROAD MAP FOR THE FUTURE
DIRECTION OF THE DIVISION OF
INTRAMURAL RESEARCH.
PREVIOUSLY, WE'VE DESCRIBED THIS
AS A STRATEGIC PLAN.
WE DECIDED TO CHANGE THE LABEL
FOR VARIOUS REASONS BECAUSE
STRATEGIC PLANS AT NIH ARE
TYPICALLY DONE AT THE IC LEVEL
AND NOT AT THE DIVISION LEVEL.
AND SO TO AVOID ANY KIND OF
CONFUSION WE JUST BASICALLY
CHANGED THE NAME TO ROAD MAP
RATHER THAN STRATEGIC PLAN.
THE OVER ALL GOALS I THINK ARE
THE SAME TO PROVIDE A ROAD MAP
FOR THE FUTURE DIVISION.
WE PUT TOGETHER A PLANNING
COMMITTEE END OF 2023 INCLUDING
A MIXTURE OF SENIOR AND JUNIOR
FACULTY MEMBERS AND MALE AND
FEMALE FROM THE RESEARCH BRANCHS
AND BEGAN THE PROCESS OF
DEBATING ABOUT THE DIFFERENT
COMPONENTS WE WOULD WANT TO
INCLUDE IN THE STRATEGIC PLAN OR
IN A ROAD MAP AND START WORKING
ON THAT PROCESS.
IN THE SUMMER WE HOSTED A TWO
HAD OF DAY ON SITE RETREAT THAT
INCLUDED NOT ONLY OUR
INVESTIGATORS AND SELECT STAFF
MEMBERS AND POSTDOCTORAL
TRAINEES, OUT ALSO KEY MEMBERS
OF THE NLM LEADERSHIP.
WE ALSO INVITED THE BOARD OF
SCIENTIFIC COUNSELORS AND
SEVERAL OF YOU ALSO ATTENDED A
DEDICATED SESSION FOR THE BOARD
TO PROVIDE YOUR PERSPECTIVE ON
STRATEGIC DIRECTION FOR US.
THROUGH THAT PROFESSION WE
CONDUCTED ANALYSIS TO DEFINE THE
CURRENT STRENGTHS AND WEAKNESSES
OF OUR DIVISION AND IDENTIFIED
OPPORTUNITIES AND THREATS ABOUT
HOW WE MIGHT WANT TO PROCEED
MOVING FORWARD.
AS A RESULT OF THAT, WE PUT
TOGETHER SOME KEY GOALS AND
OBJECTIVES AND PUT TOGETHER A
MISSION AND VISION STATEMENT
THAT WE ARE USING AS KIND OF THE
FOUNDATION FOR THIS ROAD MAP.
SO WE'RE IN THE MIDDLE OF THE
PROCESS NOW AND ONGOING
REFINEMENT TO THE ROAD MAP BUT I
WANTED TO GIVE YOU A QUICK
SUMMARY OF THE VISION AND
MISSION STATEMENTS SO YOU CAN
KIND OF SEE WHERE WE STAND WITH
DEVELOPING THOSE COMPONENTS OF
THE ROAD MAP.
THESE ARE DRAFTS BUT WE SPENT A
FAIR AMOUNT OF TIME GOING
THROUGH THESE.
IN TERMS OF OUR VISION, WE WANT
TO GROW AS A CENTER OF
EXCELLENCE FOR INNOVATION AND
COMPUTATIONAL BIOLOGY AND HEALTH
INFORMATICS RESEARCH WHERE
INVESTIGATORS ENGAGE IN A
VIBRANT, DIVERSE COLLABORATIVE
COMMUNITY TO ADVANCE BIOMEDICAL
KNOWLEDGE AND IMPROVE HUMAN
HEALTH.
TO REALIZE THAT VISION, OUR
MISSION IS TO RESEARCH AND
DEVELOP COMPUTATIONAL APPROACHES
TO BROAD RANGE OF INFORMATION
AND DATA SCIENCE PROBLEMS IN
BIOLOGY, BIO MEDICINE AND HUMAN
HEALTH LEVERAGING THE UNIQUE
RESOURCES WE HAVE HERE AT THE
NATIONAL LIBRARY OF MEDICINE.
AS PART OF THIS MISSION, WE
PROMOTE THE FIELDS OF
COMPUTATIONAL BIOLOGY AND HEALTH
INFORMATICS THROUGH OUTREACH AND
TRAINING OPPORTUNITIES TO FOSTER
AN ENVIRONMENT THAT ATTRACTS THE
DIVERSE TALENT AND PERSPECTIVE
NEEDED TO TACKLE THESE
CHALLENGING BIOMEDICAL PROBLEMS.
SO THERE'S A LOT OF INFORMATION
PACKED INTO THESE VISION AND
MISSION STATEMENTS BUT WE REALLY
FEEL LIKE THESE REFLECT WHERE WE
WANT TO TAKE OUR DIVISION MOVING
FORWARD.
TO COMPLIMENT THOSE VISION AND
MISSION STATEMENTS WE IDENTIFIED
SIX HIGH-LEVEL GOALS WITH A
NUMBER OF SPECIFIC OBJECTIVES
FOR EACH GOAL.
I'M NOT GOING TO GO THROUGH ALL
THE DETAILS IN THIS SLIDE.
I'LL BE HAPPY TO SHARE THE
SLIDES WITH THE BOARD AFTER THE
MEETING BUT THE SIX MAIN GOALS
ARE TO FIRST AND FOREMOST GROW
THE DIVISION'S COMPUTATIONAL
RESEARCH PORTFOLIO.
THE SECOND IS TO ADVANCE
INNOVATIVE PROJECTS BY
COLLABORATING WITH THE
ENGINEERING BRANCHES AT THE
NATIONAL LIBRARY OF MEDICINE.
TO TRANSLATE SOME OF OUR
VALIDATED COMPUTATIONAL METHODS
AND RESOURCES TO PRODUCTION
LEVEL SYSTEMS AS WE DO ROUTINELY
THROUGH NCBI AND LISTER HILL.
AND THE THIRD GOAL IS TO
CONTINUE TO TRAIN THE NEXT
GENERATION OF INFORMATICS
RESEARCHERS.
THE FOURTH IS TO RAISE THE
VISIBILITY OF THE RESEARCH THAT
WE ENGAGE IN IN OUR DIVISION
THROUGH DIFFERENT KIND OF
OUTREACH ACTIVITIES.
THE FIFTH IS TO ENABLE A ROBUST
DEI ENVIRONMENT WHERE WE
RECOGNIZE THE VALUE OF DIVERSE
PERSPECTIVES AND FOSTERING THE
RESEARCH THAT WE PURSUE IN OUR
DIVISION AND FINALLY, AS PART OF
THE REORGANIZATION OF OUR
DIVISION TO MODERNIZE HOW WE
ADMINISTER THAT DIVISION TO
INCLUDE THINGS LIKE USING MODERN
APPROACHES FOR BUDGET MANAGEMENT
TO COMPUTE THE RESOURCES WE NEED
AND OTHER ASPECTS OF DIVISIONAL
ADMINISTRATION.
AND ON MY LAST SLIDE, THIS IS
WHERE WE STAND WITH THE ROAD MAP
NOW AND THE NEXT STEPS.
SO WE ARE IN THE PROCESS OF
COMPLETING AN INITIAL DRAFT OF
THE ROAD MAP DOCUMENT.
AND WE'RE HOPING TO HAVE THAT
COMPLETED SOME TIME IN DECEMBER
SO NEXT MONTH.
ONCE WE HAVE A DRAFT OF THE ROAD
MAP, WE ARE PLANNING ON SHARING
THAT WITH NLM LEADERSHIP, WITH
OUR BOARD OF REGENTS AND WITH
YOU ALL AS THE BOARD OF
SCIENTIFIC COUNSELORS TO SOLICIT
YOUR FEEDBACK AND
RECOMMENDATIONS ABOUT ANY
ADJUSTMENTS WE MIGHT WANT TO
MAKE WITH THE ROAD MAP BASED ON
YOUR PERSPECTIVES.
AND THEN AS WE ARE DOING THAT
FINAL REVIEW, WE WILL ALSO BE
ADDING INTO THE ROAD MAP AN
IMPLEMENTATION PLAN AND METRICS
TO HAVE SPECIFIC GUIDANCE HOW
WE'RE PLANNING TO IMPLEMENT THE
GOALS AND OBJECTIVES AND WHAT
METRICS WE'LL USE TO ASSESS
WHETHER WE'RE ACHIEVING THE
GOALS AND OBJECTIVES AS WE
PROCEED WITH THE ROAD MAP.
SO WE'RE HOPING TO HAVE THE
FINAL ROAD MAP DOCUMENT
COMPLETED BY MARCH AND BEGIN THE
IMPLEMENTATION IN APRIL OF 2025.
SO WITH THAT, I'M HAPPY TO
ANSWER ANY QUESTIONS FROM THE
BOARD AND AGAIN, THANKS FOR YOUR
CONTRIBUTIONS.
PETER, I'LL TURN IT BACK TO YOU.
>> I'LL GIVE A SECOND IF THERE'S
ANY QUESTIONS FROM THE BOARD
OTHER MEMBERS OF THE AUDIENCE.
>> I HAVE A QUICK QUESTION FOR
RICHARD IF YOU CAN TELL US ABOUT
THE SCOPE OF THE COMPUTATIONAL
HEALTH BRANCH COMPARED TO THE
COMPUTATIONAL BIOLOGY BRANCH.
>> THANKS FOR THAT QUESTION.
THE COMPUTATIONAL HEALTH
RESEARCH BRANCH HAS BEEN
FOCUSSED ON A LOT OF THE
CLINICAL APPLICATIONS OF
INFORMATICS METHODS.
THEY ARE WORK WITH ELECTRONIC
HEALTH RECORD SYSTEMS, WITH
CLAIMS DATA, A LOT OF DATA
RELATED TO PATIENT MANAGEMENT
AND CLINICAL APPLICATIONS OF
INFORMATICS.
THE COMPUTATIONAL BIOLOGY
BRANCHES FOCUS MORE ON THE
MOLECULAR AND BASIC
COMPUTATIONAL RESEARCH LIKE
LOOKING AT PARKING STRUCTURE
PREDICTIONS, LOOKING AT AND
YOU'LL HEAR MORE FROM TERESA AND
EUGENE PART OF THAT CBB BRANCH
LOOKING AT THINGS LIKE VIRUS
EVOLUTION AND MUTATIONS IN THE
SETTING OF CANCER AND TRYING TO
UNDERSTAND THE MECHANISTIC UNDER
PINNINGS OF THOSE DISEASES.
THE THING I'M EXCITED ABOUT
WITHIN THE ORGANIZATION IS I
THINK THOSE AREAS HAVE BEEN S
SILOED IN THE PAST AND HAVE AN
OPPORTUNITY TO THINK HOW TO
BRING TOGETHER THE MOLECULAR
MECHANISTIC FEATURES AND HELP
UNDERSTAND WHAT'S GOING ON IN
THE CLINIC WITH PATIENTS AND
PROVIDE THE TRANSLATION BETWEEN
BASIC AND CLINICAL RESEARCH
THROUGH OUR NEW COMBINED
DIVISION.
I THINK THAT'S ONE OF THE
OPPORTUNITIES PRESENTING ITSELF
TO US.
>> GREAT, TO KEEP ON TRACK I'D
LIKE TO INVITE DR. KOONIN TO
GIVE HIS PRESENTATION.
>> THANK YOU.
I'D LIKE TO ECHO DR. SCHEUERMANN
IN THANKING MEMBERS OF THE BOARD
FOR THE IMPORTANT WORK AND I
APPRECIATE THIS OPPORTUNITY TO
SHARE SOME OF THE RESULTS OF THE
RESEARCH DONE IN MY GROUP FOR
THE LAST FOUR YEARS.
LET ME SHARE MY SCREEN.
CAN YOU SEE MY SCREEN?
>> YES, WE CAN.
>> EXCELLENT.
FOR MY PRESENTATION TODAY BASE
KWLI -- I'LL SPEAK TO THE
DISCOVERY OF NOVEL VIRUSES AND
ANTIVIRUS IMMUNE AND METAGENOME
MINING AND LOOKING AT THE
EVOLUTION OF THE RESEARCH.
BEFORE I PROCEED DIRECTLY TO THE
TOPIC OF MY PRESENTATION TODAY,
I WOULD LIKE TO LIST THE
RESEARCH DIRECTIONS OF MY
RESEARCH GROUP.
YOU HAVE THE BOARD MEMBERS ROOM
AND DESCRIPTIONS OF THE BOARD
AND THERE'S A CHANCE IN THE
SPACE TO COVER ALL OF THIS AND
THE SUBJECT OF THE PRESENTATION
AND ADDITIONAL SLIDES CAN BE
SEEN LATER IN THE POSTER
PRESENTATION OF DR. LEE AND THE
EVOLUTION AND TAXONOMY OF
VIRUSES AND EVOLUTION AND
INTERVENTION OF ANTIVIRUS
DEFENSE SYSTEMS AND THEORY OF
MICROBIAL GENOME AND EVOLUTION
OF CANCER AND EVOLUTION OF
BIOLOGY COMPLEXITY AND HEAR
ABOUT THE REPORT.
SO, STARTING WITH THE SUBJECT,
THIS IS SOMETHING THAT HAS
HAPPENED AND BEING PUBLISHED IN
THE PREVIOUS RESEARCH CYCLE
2017.
AND THERE'S BEEN VIRUSES AND
GENOMES ASSEMBLED FROM
METAGENOMIC AND
METATRANSCRIPTOMIC DATA AND THIS
WAS A NECESSARY DECISION BECAUSE
EVEN AT THE TIME SEVERAL YEARS
AGO, METAGENOMIC AND
TRANSCRIPTOMICS BECAME BY FAR
THE MOST IMPORTANT SOURCE IN THE
DISCOVERY OF NEW VIRUSES.
AND THIS CAN BE ILLUSTRATED BY
THIS PLOT SHOWING THE VIRUSES
AND YOU CAN SEE THE SAMPLE OF
THOSE NOT ONLY FROM
METAGENOMICS.
YOU CAN SEE AND I DIDN'T DATE
THE SLIDE BUT IF I DID YOU WOULD
NOTICE THESE DOTS BECAUSE
OVERWHELMINGLY WE LOOK AT
METAGENOMICS AND
TRANSCRIPTOMICS.
THE FIRST TO HIGHLIGHT I WANT TO
BRING TO YOUR ATTENTION TODAY IS
EXTENSIVE ANALYSIS OF MORE THAN
3,000 TRANSCRIPTOMICS AND
REPRESENT
REPRESENTING THE DISCOVERY OF
NOVEL RNA VIRUSES.
FOR ALL THESE INVESTIGATIONS
THERE'S COMPUTATION AND THEY
ESSENTIALLY USE THE PROFILES OF
POLYMERASES THE GENE SHARED BY
ALL RNA VIRUSES TO IDENTIFY THE
METATRANSCRIPTOMICS AND WHAT WE
DISCOVERED HERE I DID HIGHLIGHTS
ON THE NEXT SLIDE OR TWO BUT I
WANT TO EMPHASIZE THE MAIN
MESSAGE THAT WE GREATLY EXPANDED
THE DIVERSITY AND CHEER NUMBER
OF.
AGENTS AND RNA VIRUSES THAT CAN
SEE AND THE EUKARYOTIC SEQUENCES
AND THE MAIN COMPONENT AND THE
PRESENCE OF THE BACTERIA YOU
SHOULD SEE IN THE PAPER THIS IS
SIMPLY NOT SO.
AND THIS HAS BEEN INVOLVED IN
PREVIOUS STUDIES AND THE VIRUSES
FROM ALL OVER THE WORLD AND IN
BOTH KINDS OF SYSTEMS.
SO, IT'S FIVE TO SIX FOLD
INCREASE OF THEIR DIVERSITY OF
RNA VIRUSES.
AND WE ASSESSED THE VIRUSES AND
WE HAVE ONLY A SMALL AND THERE
WAS A STANDARD INCREASE IN THE
DIVERSITY OF RNA BEFORE WE HAD
THE STUDY.
AND WE SHOW HERE AND THESE ARE
WHAT I WANT TO BRING THE MOST
ATTENTION TO AND THE RNA VIRUS
AND GENOME INDICATING IN TERMS
OF THE DIVERSITY OF THE SPECIES
WE'RE STILL SCRATCHING THE
SURFACE AND WE TALK ABOUT THESE
WHERE WE DISCOVERED THE RNA
VIRU
VIRUSES THEY'RE ASSOCIATED WITH
BACTERIA AND WHAT IS MOST
INTERESTING IS THERE'S
POLYMERASE SHOWN AND WE PRESENT
AN INTERMEDIATE STAGE OF
EVOLUTION BETWEEN THE POLYMERASE
AND TRANSCRIPTASE AND TWO OF THE
VIRUS THAT NEEDS TO BE
DISCOVERED.
I WILL NOW SWITCH TO SOMETHING
EVEN MORE UNUSUAL AND DON'T USE
THIS SLIDE FROM THE QR CODE
PUBLISHED AND INTRODUCE THESE
AROUND VIROID ARE AND BASICALLY
MAKE RNA AND LOOK AT THESE AND
OTHERWISE WE RELY ON UNUSUAL
REPLICATORS OF AGENTS AND mRNA
AND RIBOZYVIRUS AND THIS
INTERESTING AND THEY'RE
IMPORTANT AND THEY'RE ASSOCIATED
WITH HEPATITIS B AND AND CAN
CAUSE DISEASE BUT THESE DO NOT
GET VERY MUCH TRACTION.
WE DECIDED TO TRY TO FIGURE OUT
BY TRANSCRIPTOMES COULD IT BE A
MUCH GREATER DIVERSITY OF AGENTS
WELL BEFORE EMBARKING DIRECTLY
ON THE OF AND THE DATABASE CAN
BE USED FOR THE SEQUENCES AND
DISCOVER RIBO ZY RNA AND
DISCOVER TO IDENTIFY THE RNA AND
MAKE SURE THEY ACTUALLY DETECT
THOUGH THE VIROID HAS BEEN
DEVELOPED AND WE APPLIED IT FOR
THE DISCOVERY OF RNA VIRUSES.
AND THEY ALSO EVOLVED BY THE
EXTENSION OF VIROID LIKE RNAs
BUT THE MOST IMPORTANT HAS BEEN
DISCOVERED MANY ARE DEVOID OF
ANYMORE MATERIAL SUGGEST IING T
DIVERSITY OF EDGES ARE LIKELY TO
IMPACT THESE AND HAVE TO SHOW
SOME ARE TARGETED INDICATING
THEY PRODUCE PROKARYOTES.
SO THERE'S ROUGHLY SIX FOLD
EXTENSION OF THE DIVERSITY AND
CLOSE RNAs.
AND SOME ARE LIKELY VIRUSES AND
HAVE ENORMOUS AMOUNTS OF DARK
MATTER AND NEED TO BE
INVESTIGATED.
SO, WE DISCOVERED THE NUCLEIC
ACID AND THIS IS DISCOVERED IN
THIS SPACE.
VERY INTERESTING WE ALSO
IDENTIFIED A NOVEL VARIETY OF
VIRUSES AND THIS WAS PREVIOUSLY
KNOWN WITH THE FUNGI BUT HAVEN'T
BEEN REALIZED CONTAINING
RIBOZYMES AND MANY SEQUENCES OF
SUCH.
THEY ENCODE AND THE GENOME HAVE
BEEN INVOLVED AND VIRUSES PUT
THE TAXONOMY NEEDS TO BE
RESOLVED.
SO OUR HYPOTHESIS THERE'S VIROID
LIKE ROLES AND RNAs AND RIBO
VIRUSES THAT ARE PROTEIN ENCODED
GENES THESE FINDINGS AND TO DATE
THERE'S DISCOVERIES OF THE
DIVERSITY OF SUCH AGENTS AND I
THINK THE IDEA NEED TO BE SEEN
AND WE NEED TO TALK ABOUT THE
MOST ABUNDANT HUMAN ASSOCIATED
VIRUSES.
SO THE MOST IMPORTANT HUMAN
ASSOCIATED VIRUS IS THE
SO-CALLED CRASSPHAGE AND THIS
CAN BE DISCOVERED AND THE
VIRUSES CAN COMPRISE UP TO 90%
OF VIRUS SEQUENCES IN OUR GUT
MICROBIOME AND WE'RE INTERESTED
IN THESE VIRUSES AND WE NEED TO
ANALYZE THE GENOMES AND DISCOVER
THE PROMISE OR IMPORTANTLY
DISCOVER THE WHOLE FAMILY OF
THESE VIRUSES BEING ASSOCIATED.
WITH THIS EXTENDED THE STUDIES
ARE COMPRISED IN THE ORDER OF
VIRUSES AND WE LOOK AT MANY
INTERRUPTED GENES AND GENETIC
CODES AND MORE AND MORE THAT
REMAINS TO BE INVESTIGATED.
THESE ARE EXTREMELY ABUNDANT IN
OUR GUT AND UP TO 90% OF THE
VIRUS SEQUENCES.
NOW RECENTLY WITH OUR COLLEAGUES
FROM THE UNITED KINGDOM HAVE
INVOLVED IN STRUCTURAL
CHARACTERIZATION OF THE VIRUSES
AND CREATING THE STAGE AND
REPEATING VERY INTERESTING
UNUSUAL FEATURE OF MULTIPLE
PROTEINS INJECTED IN THE
INFECTED CELLS AND THE VIRAL
GENE INCLUDING THE POLYMERASE OF
EARLY GENES AND BEFORE I FINISH
THE DISCUSSION DISCOVER THE
METAGENOMES AND TRANSCRIPTOMES I
WANT TO INTRODUCE THIS
INFORMATIVEST --INFORMATIVE
ESTIMATES AND LOOK AT THE NUMBER
OF VIRUSES ASSOCIATED UNEACH
SPECIES AND THIS IS A LARGE
NUMBER AND AROUND THE NUMBER OF
DISTINCT VIRAL GENES THEY
PROBABLY EXCEED BY DECENT ORDER
OF MAGNITUDE THE NUMBER OF GENES
THAT ARE TARGETS INDICATED THE
VIRUS IN PARTICULAR ARE THE MAIN
RESERVOIR OF GENETIC DIVERSITY.
BEFORE I FINISH MY TALK, LAST
BUT NOT LEAST I WOULD LIKE TO
HIGHLIGHT THIS WORK IN
COLLABORA
COLLABORATION AND THE DISCOVERY
OF ANTIVIRAL DEFENSE SYSTEMS
WE'VE BEEN TALKING ABOUT FOR 25
MINUTES OR SO NOW WE LOOK AT THE
DEFENSE SYSTEMS AND I DON'T
THINK I NEED TO INTRODUCE CRISPR
DISCOVERY AS THE MOST EFFICIENT
AND WE CAN INCREASE DISCOVERY
FOR MANY YEARS BUT HERE IN
COLLABORATION TO TAKE THIS
ANALYSIS TO A DIFFERENT LEVEL
AND ANALYZE GENOMIC SEQUENCES TO
DISCOVER NOVEL PERSISTENCE WE
CAN INTRODUCE AN EFFICIENT
METHOD OF MILLIONS OF SEQUENCES
FROM METAGENOME OTHERWISE THIS
SIMPLY CANNOT HANDLE THE SEARCHS
OF THESE DATAS.
SO WE LOOK AT THE DISCOVER AND
DEVELOPED RESULTING IN THE
DISCOVERY OF NOVEL CRISPR
VARIANTS AND CRISPR ASSOCIATED
GENES AND THIS TIME LINE HERE
SHOWS WHAT WE DISCOVER IN THE
PAPER AND THE DATABASES.
WE CAN SEE THE MAJORITY OF THERE
IN THE LAST DECADE EMPHASIZING
CRUCIAL IMPORTANCE OF THE
IMPORTANCE OF METAGENOMIC
DATABASES.
ONE OF THE DISCOVERIES IS
ANOTHER TYPE OF CRISPR AND THIS
CONTAINS A LOT OF EFFECT OF THE
NUCLEASE NOT PREVIOUSLY DETECTED
IN SYSTEMS AND OUR COLLEAGUES
ACTUALLY DEMONSTRATED THIS
EFFECT.
SO MY SYSTEMS ARE IMPORTANT AND
IN PARTICULAR LOOKING AT IN
PARTICULAR CRISPR AROUND WHAT
NEEDS TO BE DEVELOPED NEW
METHODS AND LIKE WHAT IS BEING
DEVELOPED ALTOGETHER THEY
DISCOVER NEARLY PREVIOUSLY
REPORTED CRISPR GENE MODULES AND
SOME OF WHICH ARE INCLUDE D CAN
BE VALIDATED IN THE WORK.
LET ME MAKE SOME GENERAL
CONCLUSIONS.
THIS REVEALS DIVERSITY OF
VIRUSES AND OTHER GENETIC
ELEMENTS AND VIRUSES AND
CONVERSELY THE VIRUS DEFENSE
SYSTEMS.
THE REVIEW BY METAGENOMICS AND
META TRANSCRIPTOMICS IS NOT ONLY
QUALITATIVE BUT QUANTITATIVE AND
NEW AGENTS AND TYPES OF CRISPR.
IT HAS TO BE NOTED HOWEVER, THAT
THE MOST ADVANCED GROUPS AND
TYPES OF CHRIS PER SYSTEMS ARE
ALREADY KNOWN FOR THEIR
STABILITY AND TAXONOMY OF THESE
VIRUSES AND SYSTEMS AND THEY'RE
NOW LOOKING AT THE DIVERSITY
DISTRIBUTION AND DOESN'T MAKE
THE DISCOVERIES LESS INTERESTING
AT ALL.
WE HAVE UNPRECEDENTED
OPPORTUNITIES FOR BIODIVERSITY
AND EVOLUTION WE'LL PURSUE
VIGOROUSLY.
SO AND WE HAVE RELEASED THREE
INSTALLMENTS OVER THE YEARS AND
DISCOVERY NEEDS TO BE DISCOVERED
AND APPROVED AND FUNCTIONALLY
IMPORTANT PROTEINS AND BACTERIA
A
AND OF COURSE I DEVIATE ON THE
IMMEDIATE SUBJECT OF THE TALK
AND DISCUSS THE EUKARYOTIC GENES
AND MORE PLANS EFFICIENT A.I.
BASED APPROACH FOR MINING META
GENOMES AND META TRANSCRIPT
OMICS AND EXTENDING BIODIVERSITY
AND CO-EVOLUTION OF GENETIC
PARASITES AND THEORY MODELS AND
ANALYSIS OF PATTERNS AND MORE
GENERAL STUDIES OF THE ORIGIN OF
LIFE AND I I MUST ACKNOWLEDGE
MEMBERS OF MY GROUP HERE.
AND LOOK AT THE RELATED RESEARCH
AND MY MANY COLLABORATORS FROM
MANY PARTS OF THE WORLD FOR WHOM
I'M GRATEFUL AND THANK YOU VERY
MUCH FOR YOUR ATTENTION AND I'LL
BE DELIGHTED TO ANSWER ANY
QUESTIONS YOU PLAY HAVE.
-- YOU MAY HAVE.
>> GREAT, WE TURNED OFF
DR. KOONIN'S VIDEO BECAUSE OF
BANDWIDTH BUT PERHAPS FOR Q&A WE
CAN PUT THE VIDEO BACK ON.
I'LL TURN IT OVER TO QUESTIONS
AND ANSWERS.
>> UNFORTUNATELY, MAY BE
>> OKAY.
SO WHY DON'T WE START WITH
ANYBODY FROM THE GENERAL
AUDIENCE.
SO, WE'VE GOT ABOUT 15 MINUTES
FOR QUESTIONS FROM THE BOARD OF
SCIENTIFIC COUNSELORS AND
GENERAL AUDIENCE AND AT 12:20
EASTERN WELL CUT OVER TO THE
POSTER SESSION AND POSTDOCTORAL
FELLOWS.
>> I HAVE A QUICK QUESTION.
>> GO FOR IT.
>> SO, EUGENE, YOU ELUDED TO THE
ORIGINS OF LIFE IN YOUR TALK.
COULD YOU EXPAND A LITTLE BIT
ABOUT THAT THEORY AND GO BACK AS
AS FAR AS POSSIBLE IN TIME OR
YOUR THOUGHTS.
>> WELL, YES, OF COURSE.
THERE'S A STUDY TRYING TO
DEVELOP IN TERMS OF EMPIRICAL
PROJECT I THINK THE NOVEL
RIBOZYMES THAT ENABLE ACTIVITIES
WE NEED UNDERSTANDING AND
THERE'S RECONSTRUCTION OF THE
PRIMORDIAL AND THEORETICAL
MODELS ON THE ORIGIN OF LIFE IT
INVOLVES THE SYMBIOTIC ORIGIN OF
LIFE AND SYMBIOTIC RELATIONSHIP
BETWEEN PRIMORDIAL REPLICATOR
CELLS THAT STILL LACK ANY GENOME
TO REPRODUCE BY SIMPLE PHYSICAL
DIVISION.
AND THE MOST DIFFICULT PROBLEM
IN BIOLOGY FROM A DIFFERENT
STANDPOINT.
>> THANKS.
>> I HAVE A QUESTION WHICH
RELATES TO YOUR TALKING ABOUT
HAVING IDENTIFIED THE NUMBER OF
UNREPORTED CRISPR-LIKE GENE
MODULES RAND I'D LIKE TO HEAR
MORE WHAT THE PRACTICAL
IMPLICATIONS OF HAVING
IDENTIFIED WHAT THESE ARE.
HOW DO YOU ENVISION THE
PRACTICAL LOCATIONS OF IT AND
THE SCIENTIFIC IMPLICATIONS OF
IT.
>> THEY'RE FUNDAMENTALLY
IMPLICATI
IMPLICAT
IMPLICATIONS IN TERMS OF
FUNDAMENTAL IMPLICATIONS, WE SEE
ADDITIONAL ENZYMES AND WE
DISCOVER VARIETIES OF THE
NUCLEASES INDICATING THAT THESE
ARE INDEPENDENT INVESTIGATION OF
THESE SYSTEMS AND LOOK AT THE
SYSTEM TYPES ARE QUITE OF THE
CRISPR COMMON IN NATURE AND FROM
AN EVOLUTIONARY STANDPOINT WE
UNDERSTAND SOME ARE SO
SUCCESSFUL AND OTHERS ARE MUCH
LOWER, MUCH LESS CALLED AND
THEY'RE MORE RARE VARIANTS DON'T
IMPLY IN PARTICULAR AND SOME OF
THEM ARE NEWLY DISCOVERED OVER
THE DECADES OF OBTAINING THE
SO-CALLED HMH NUCLEASE CAN BE
VERY PRECISE OF DNA AND
INTRODUCING OFF TARGET AND IT'S
NOT EASY TO INTRODUCE A NOVEL
TOOL BECAUSE THE POTENTIAL IS
THERE NEVERTHELESS THIS CAN BE
SIGNIFICANTLY DONE.
>> RICHARD AND THEN NOMI AND
THEN TIME FOR ONE OR TWO AFTER
THAT AS WE'RE TRYING TO WRAP UP
IN ABOUT SEVEN MINUTES.
>> GREAT, THANKS.
THANKS, EUGENE.
I WONDER IF YOU COULD COMMENT ON
THE IMPACT THAT SAMPLING BIAS
HAS ON YOUR ESTIMATES OF VIRUS
DIVERSITY.
>> IT'S ALWAYS AN ISSUE.
HOWEVER, I THINK IT'S RAPIDLY
BECOMING MUCH LESS.
BECAUSE THEY ARE HAVE
ENVIRONMENTS REPRESENTED AND
THERE'S MANY THOUSANDS OF
TRANSCRIPT OME S REPRESENTING
ALL KIND OF ENVIRONMENTS.
A
AND THEY'RE MOVING TOWARDS
UNBIASSED ANALYSIS.
THAT BEING SAID THOSE THE
DISTINCT ENVIRONMENT VERY
INTERESTING THINGS MOREOVER SOME
OPTIMISTIC BIAS SAMPLES ARE
DIFFERENT KINDS OF COSTS OF
DIFFERENT ANIMALS.
FOR INSTANCE WITH YOU KNOW
LITTLE ABOUT THE VIRUSES
INFECTING ABOUT YEUKARYOTES AND
CAN BE DISCOVERED AND LESS
EXOTIC SAMPLES AND VARIETIES
COME UP.
SO THERE'S STILL A LOT THAT
NEED TO BE RECOVERED.
>> THANK YOU.
>> DR. KOONIN, THANK YOU FOR
YOUR PRESENTATION AND YOUR
RESEARCH.
THIS IS NOT MY AREA OF RESEARCH
AND MY QUESTION WAS SOMEWHAT
RELATED TO THE PREVIOUS QUESTION
WHICH IS AS YOU IDENTIFY THIS
DRAMATIC INCREASE IN VARIED
ELEMENTS AND THIS WAS BASED ON
THE DATA YOU HAD ACCESS TO WHICH
WAS DIVERSE BUT STILL A FINITE
SITE OF DATA.
WHAT IS YOUR EXPECTATION AS HOW
MANY MORE TYPES OF DATA WOULD BE
USEFUL TO LOOK AT AND YOU
MENTIONED JUST NOW DIFFERENT
ENVIRONMENTS IN TERMS OF THE
AMOUNT OF DATA, WHAT IS THE
SCALE YOU'RE LOOKING AT AND HOW
HARD IS IT TO ASSEMBLE THE DATA
SETS?
>> THANK YOU FOR THE QUESTION.
THERE'S A BUNCH OF THEM.
HERE WE HAVE EFFECT I THINK WE
CAN DEVELOP EFFECTIVE METHODS
AND I THINK AND COMING BACK TO
DR. SCHEUERMANN IT'S OF COURSE
IMPORTANT TO EXPLORE
TRANSCRIPTOMES AND HERE THEY'RE
STILL LAGGING BEHIND A LOT AND
NEEDS TO BE DONE AND EVEN IN THE
WORK WE HAVE DONE AS I
MENTIONED, THERE ARE PROBABLY
SEVERAL WHERE WE'RE TRYING TO BE
VERY SURE WE KNOW WHAT WE'RE
LOOKING.
BUT THERE'S AN ENORMOUS AMOUNT
OF DATA AND WE'RE LOOKING RIGHT
NOW AND WE HAVE OBSERVATIONS
WITH INTERESTING DISCOVERIES
WILL BE MADE.
SO, IT'S SORT OF DOUBLE EVEN IN
WHAT WE HAVE THERE IS STILL A
LOT TO DIG IN AND THEY'LL BE
INTERESTING FOR SURE.
BUT THERE'S ROOM FOR OR SO.
>> THANK YOU.
>> I DON'T KNOW -- IS IT OKAY IF
I ASK A QUESTION?
>> GO AHEAD.
>> HI, EUGENE, EXCELLENT TALK AS
ALWAYS.
NICE SEEING YOU THERE.
MY QUESTION IS IF YOU WERE TO
PREDICT WHAT WILL BE THE NEXT
NOBEL PRIZE IN YOUR AREA, WHAT
DO YOU THINK WOULD BE THE MAJOR
DISCOVERY AND HOW YOUR TEAM HAD
HELP TO DO THAT.
>> THAT'S AN IMPORTANT QUESTION.
THE NEXT NOBEL PRIZE IN MY
FIELD -- OKAY, LET ME SAY
SOMETHING THAT MAY NOT BE
DIRECTLY RELATED TO THE RESEARCH
BUT ACTUALLY -- OKAY.
I SEE IN MY OPINION SOME ARE
NOBEL WORTH.
SOME IS MRAET GENOMICS AND
TRANSCRIPTOMICS.
I FIND IT A BIT SCANDALOUS THAT
THESE ARE REVOLUTIONARY HAVE NOT
BEEN AWARDED JUST YET.
IT MAY BE DIFFICULT TO LOOK AT
PRINCIPLE AND THERE'S
CHARACTERIZATION OF THE
STRUCTURE AND THE DIVERSITY OF
THE VIRUS WHICH CAN BE ACHIEVED
IN THE LAST FEW YEARS INCLUDIN
THE DEVELOPMENT OF THE
COMPREHENSIVE TAXONOMY.
BUT THEN IF YOU'RE TALKING ABOUT
MAJOR ACHIEVEMENTS AND JUST THIS
YEAR THE NOBEL PRIZE IN
CHEMISTRY AND AT THE SAME TIME
THE DEVELOPMENT FOR SEQUENCE AND
THIS IS A BIT PARADOXICAL.
>> THANK YOU.
>> JOHN, DO YOU WANT TO ASK YOUR
QUESTION NOW OR WAIT UNTIL THE
CLOSED SESSION?
>> I CAN ASK MAYBE IT'S OFF
TOPIC BUT I WAS INTERESTED WHEN
YOU TALKED ABOUT USING
STATISTICAL MECHANICAL APPROACH
TO COMING UP WITH A GENERALIZED
THEORY FOR EVOLUTION.
AND A GENERALIZED VERSION OF THE
CENTRAL DOGMA AND IF IT'S NOT
TOO MUCH OFF TOPIC IF YOU HAVE A
FEW MOMENTS TO COMMENT ON THAT.
>> YES, OF COURSE.
I'M ALSO APPRECIATE IIVE OF THE
OPPORTUNITY.
I'M VERY INTERESTED IN THE
THEORY AND ONCE THESE HAVE
DEVELOPED IN THE LAST TWO, THREE
YEARS IS A GENERAL FRAMEWORK
THAT IS BASED ON AS A MOTIVE OF
MACHINE LEARNING THEORY AND
EVOLUTIONARY FIELD.
THE IDEA OF THE ANALOGY BETWEEN
EVOLUTION AND DYNAMICS GOES BACK
TO 1930s.
BUT THAT WAS VERY SYSTEMATICALLY
WITH A DIRECT RELATIONSHIP
BETWEEN KEY VARIABLES AND LOOK
AT ENTROPY AND TEMPERATURE IN
EVOLUTIONARY POTENTIAL IN
EVOLUTIONARY SYSTEMS.
AND WE HAVE IT AS A PROCESS OF
MULTILEVEL WHICH APPLIES NOT
ONLY TO BIOLOGY BUT TO VARIOUS
FORMS IN THE UNIT.
THERE'S MORE SELECTION FOR
STABILITY AND IT'S STILL
APPLICABLE.
SO RESEARCH IS YOU THINK OF
DIRECT RELEVANCE FOR TRYING TO
UNDERSTAND THE ORIGIN AT A
THEORETICAL LEVEL WITH RESPECT
TO THE CENTRAL DOGMA TO KEEP
UNMIND IS A KEY GENERALIZATION
OF THE INFORMATION WHICH IS
DERIVED.
WHAT WE SHOW HERE IS A
REQUIREMENT FOR A QUICK TRANSFER
OF INFORMATION FROM THE
ENVIRONMENT AND FLOW OF
INFORMATION TO THE ENVIRONMENTAL
CUES OPPOSED TO THE MUCH SLOWER
SYMMETRICAL FLOW OF INFORMATION
FROM THE ENVIRONMENT TO THE
ORGANISM THROUGH MUTATION AND
SELECTION WHICH THE SYMMETRY IS
NECESSARY AS A STABLE MEMORY IS
ESSENTIAL FOR SUCH EVOLUTION.
>> THANK YOU.
>> THANKS, THAT WAS GREAT.
SINCE WE ARE A LITTLE BIT BEHIND
SCHEDULE AT THIS POINT, WHAT I
WOULD PROPOSE IS WE SWITCH TO
THE CLOSED POSTER SESSION WITH
THE POSTDOCTORAL FELLOWS AND FOR
OTHERS, WE WILL RETURN FOR THE
CLOSED SESSION WITH DR. KOONIN
NOT AT 12:50 BUT AT 1:00.
SO, WELCOME BACK EVERYBODY
WE'RE NOW RECONVENING THE PUBLIC
SESSION FOR DR. PRZYTYCKA'S
PRESENTATION AND I'LL TURN IT
OVER TO YOU.
>> LOOKS GOOD.
>> YOU'RE ON MUTE, HOWEVER.
>> WE'RE SEEING YOUR LIPS MOVE
BUT --
>> THANK YOU VERY MUCH.
NOW WE CAN HEAR YOU AND SEE YOU
AND SEE THE SLIDES.
>> NOT THE PRESENTATION?
>> I SEE THE FULL SLIDE NOT THE
PRESENTER VIEW.
>> OKAY.
GREAT, THANK YOU.
SO GOOD AFTERNOON, EVERYONE.
IT'S MY PLEASURE TO PRESENT TO
THE BSC COMMITTEE THE GROUP IN
THE LAST FOUR YEARS.
MY GROUP WORKING ON METHODS IN
COMPUTATIONAL AND SYSTEMS
BIOLOGY AND CURRENTLY WE HAVE
SIX GROUP MEMBERS ON DIFFERENT
CAREER LEVELS INCLUDING TWO
STAFF SCIENTISTS, HERE ONE
GRADUATE AND ONE POST-BAC AND
OTHER WORK CONTRIBUTED TO THE
CONVERSATION.
THREES FOCUS ON DEVELOPING NOVEL
ALGORITHMS TO ADDRESS BIOLOGICAL
QUESTIONS AND WORK ON ANALYSIS
AND DATA.
AND TODAY I'M GOING TO FOCUS MY
PRESENTATION ON TOPICS RELATED
TO THE INTERACTION BETWEEN MUE
-- MUTAGENIC SIGNATURES AND IN
THE CONTEXT OF EVOLUTION.
TO SET THE CONTEXT THE CURRENT
UNDERSTANDING OF THE EVOLUTION
IS TUMOR EVOLVE SO-CALLED TUMOR
INITIATING CELL IS THE CELL THAT
OBTAINS THROUGH CANCER DRIVING
MUTATION GROWS ADVANTAGE AND
BECOMES A CELL THAT DIVIDES
MAYBE OBTAINING MUTATION AND
GIVING RISE AND ALSO ALSO
EPIGENETIC CHANGES AND OTHER
TRANSCRIPTIONAL CHANGES MAY LEAD
TO NEW.
WUNLZ THAT INTERACT WITH THE
ENVIRONMENT AND THE
IMMUNOSYSTEM.
IN ADDITION TO THE GROWING TUMOR
THE CELL ACCUMULATE ALSO
MUTATION.
AND AMONG THE CELLS ALL CELLS
ARE SUBJECT TO MUTAGENIC
PROCESSES RELATED TO
ENVIRONMENT.
SOMETIMES DURING TUMOR
PROGRESSION, ACQUIRED DNA
DEFICIENCY WHICH IS A NUMBER OF
MUTATION AND ADDITIONAL
TREATMENT SUCH AS CHEMOTHERAPY
ALSO INTRODUCE ADDITIONAL
MUTATIONS.
SO TODAY I'LL START MY
PRESENTATION BY TALKING ABOUT
OUR RESULT RELATED TO ADDITIONAL
PROCESSES AND SIGNATURE.
WE'LL MOVE TO METHOD TO LOOK AT
INTERACTIONS BETWEEN TUMOR AND
ENVIRONMENT.
NEXT I'LL MENTION FRAMEWORK ON
ADAPTATION OF GENE EXPRESSION IN
CLONAL EVOLUTION WITH
APPLICATION TO MELANOMA AND
BRIEFLY MENTION ANOTHER PROJECT.
THE.
AND I'LL MENTION THEM IN THE
PLACES WHERE THEY MOST NATURALLY
ACCOMPLISH AS SUCH.
I'LL START TO THE FIRST TOPIC
WHICH IS MUTATION PROCESSES AND
MUTATION SIGNATURE.
MY GROUP HAS BEEN WORKING ON
THIS FOR QUITE SOME TIME SO
TODAY I'LL JUST PRESENT RESULTS
FROM THE LAST FOUR YEARS.
SO, THOUGH MUTATION THE IDEA OF
MUTATIONAL SIGNATURE HAS BEEN
AROUND FOR SOME TIME AND MAY NOT
BE BROADLY KNOWN SO LET THE
START BY EXPLAINING THE CONCEPT.
IT'S BEEN APPRECIATED FOR A LONG
TIME SPECIFIC MUTAGENIC
PROCESSES LEAVE SPECIFIC IMPRINT
ON THE DNA OF THE GENOME.
FOR EXAMPLE, IT'S KNOWN TO
PARTICULAR MUTATION WHERE IT'S
PROCEEDED BY T.
SMOKING WILL HAVE A DIFFERENT
OUTCOME AND HAS A CHARACTERISTIC
PATTERN.
THIS LED TO AN IDEA THAT PERHAPS
WE CAN ASSOCIATION MUTATIONAL
SIGNATURES TO LOOK AT THE GENOME
AND LOOK AT THE SIGNATURES AND
UNDERSTAND SOMETHING ABOUT THE
MUTAGENIC PROCESSES THAT MIGHT
HAVE INFLUENCED THE CURRENT
STATE OF THE GENOME.
WE START WITH THE CATEGORY WHERE
MUTATION POSITION LEFT AND RIGHT
INTRODUCE THE CONTEXT.
SO IN THIS WAY OTHER MUTATION
CAN BE ASSIGNED TO ONE CATEGORY
UNLESS WE HAVE MUTATION
CATEGORIES WE DEFINE SIGNATURE
AS A DISTRIBUTION OF MUTATIONAL
CATEGORIES WITH CHARACTERISTIC
TO A MUTAGENIC PROCESS AND WE
HAVE SIGNATURE EXPOSURE.
LOOKING AT THE INDIVIDUAL
GENOME, WE CAN NOW ASSIGN
VARIOUS MUTATIONS TO VARIOUS
SIGNATURES AND THE NUMBER IN THE
GENOME ATTRIBUTED TO THE
DIFFERENT SIGNATURE IS CALLED
THE EXPOSURE.
SOMETIMES WITH THE NUMBER
PROPORTION.
HERE YOU HAVE THE UV LIGHT
SIGNATURE ONE THIS MUTATION.
WHY DO WE CARE?
WELL, WE ARE LOOKING THROUGH THE
LENSES OF THE MUTATIONAL
SIGNATURES HOPING TO UNDERSTAND
MUTAGENIC PROCESSES THAT HAPPEN
IN CANCER.
IN ADDITION, MUTATIONAL
SIGNATURE ON THE GENOME HAVE
SHOWN TO BE PREDICTIVE OF THE
RESPONSE TO THERAPY WHICH IS
ALSO IMPORTANT.
THE MUTATION SIGNATURES ARE
INFERRED COMPUTATIONALLY AND FOR
EACH GENOME WE SIMPLY HAVE
MUTATION CATEGORIES AND THE IDEA
IS SIMILAR TO MANY OTHER
COMPOSITION IDEA AND THE MATRIX
WHERE EVERY ROLE IS A SIGNATURE
AND THE SECOND IS THE MATTERS OF
EXPOSURES.
THERE ARE TWO MAIN WAYS OF
LOOKING AND UTILIZING THE
SIGNATURES IN THE APPLICATION.
ONE, WHEN WE HAVE NEW DATA WE
CAN USE LOOK AT THE EXPOSURES
A
AND REMEMBER WITH EFFORT TO
INFER DATA SIGNATURES OF THE
MUTATION SIGNATURES SO WE MAY
HAVE A NEW DATA SET WHERE WE
ASSUME MUTATION SIGNATURE ARE
KNOWN AND INFER.
THEN THE CHALLENGE IS RELATED TO
THIS RESEARCH.
ONE IS THAT WE HAVE THE
APPLICATION SIGNATURE
COMPUTATIONALLY AND MANY
SIGNATURES ARE UNKNOWN.
THERE'S ALSO A HIDDEN MODEL THE
ASSUMPTION THAT MUTATION
SIGNATURE AS A MUTATIONAL
PROCESSES ARE INDEPENDENT WHICH
IS AN OVER SIMPLIFICATION AND I
MENTIONED THE TWO APPROACHES TO
UTILIZE THE SIGNATURES BUT THERE
ARE EXAMPLES THAT NONE ASSUME
THE IDEA.
TO MOVE OUR RESEARCH ASSIGNMENT
WE'VE BEEN WORKING ON THIS TOPIC
MANY YEARS AND I WILL START WITH
THE CHALLENGE THAT WAS KIND OF
FOR SOME TIME IS HOW TO MODEL
THE MUTATIONAL PROCESSES NOT
INDEPENDENT.
WE FOCUS ON DNA DAMAGE AND
DEFICIENCY AND CAME UP WITH THE
FOLLOWING MODEL.
WE REPAIR THE DEFICIENCY
INDEPENDENTLY AND ASSUME THE
AMOUNT OF DNA DAMAGE WILL COME
FROM PROFESSIONS LIKE UV LIGHT
AND OTHER PROCESSES OF THIS
TYPE.
THEY FEED INTO THE DNA REPAIR
PROCESS AND IF THE DNA REPAIR
PROCESS IS DEFICIENT, IT WILL
AMPLIFY SOME OF THOSE MUTATION
IN A WAY DEPENDENT ON THE TYPE
OF DNA REPAIR.
USUALLY DON'T SEE THOSE AND SEE
THE FINAL RESULT SO THE QUESTION
IS CAN GIVEN THE MUTATIONAL
PROFILE OF A GENOME, CAN WE DO
DNA REPAIR AND MODEL AND WE CAME
UP WITH THE COMPOSITE MODEL
WHERE WE MODEL MUTATIONS IN TWO
STEPS.
ONE IS THE PRIMARY PRESUMED TO
BE INDEPENDENT AND THEN THE
SECOND PROCESSES RELATED TO THE
DNA DAMAGE SO THE MODEL BY
CHANGING THE RESULT OF THE
PRIMARY PROCESSES.
NOW WE HAVE PARAMETERS AND
MOVING PARTS BUT LET ME JUMP TO
GO TO EVALUATIONS OF THIS
APPROACH THAT WORK.
WE LOOKED AT SIGNATURES IN
BREAST CANCER AND SUSPECTED THE
SIGNATURES IN ONE IS PART OF THE
MODELS AND CAN REPLACE THE FOUR
MUTATIONAL SIGNATURE AND GET
EVEN BETTER SMALLER
APPROXIMATION AND FOR THE
EXPERIMENTAL SIGNATURES WE CAN
CONFER OUR SIGNATURE IS SIMILAR
TO THIS ONE.
THIS IS THE FORMAL MODEL OF THE
DNA DAMAGE REPAIR AND MODEL THE
PROCESSES ON THE GENOMES WHICH
WILL NOT DISCUSS TODAY.
HOWEVER, I'D LIKE TO MOVE TO THE
SECOND CHALLENGE I MENTIONED.
THE RELATIONSHIP BETWEEN THE
PROFESSIONS INTO THOSE NOT
UNDERSTAND FOR SIGNATURE.
HOW CAN WE CHANGE THE FELT THE
BEST INFORMATION OBTAINED IS TO
SEE HOW THE MUTATIONAL
SIGNATURES INTERACT WITH
MOLECULAR PATHWAYS IN PARTICULAR
TYPES.
THE IDEA OF THE WORK WAS TO
REPRESENT THE INTERACTION
BETWEEN SIGNATURES AND GENE
EXPRESSION USING A DIRECT GRAPH.
AND THE UNDERPINNING WHY WE CAN
DO IS TO CONSIDER TYPES SAY
BREAST CANCER WITH EVERY GENE WE
CAN ASSOCIATE GENE EXPRESSION
AND ACROSS THE SAME COHORT OF
PATIENTS WE CAN ASSOCIATION THE
SIGNATURES EXPOSURES.
THOUGH WE HAVE TWO TYPES, MOST
CAN BE CHARACTERIZED ACROSS
PATIENTS.
WE CAN USE THE METHODS RELATED
TO THE NETWORK TO CONSTRUCT THE
DATA AND SPECIFIC METHODS AND
THERE'S ADDITIONAL MATRIX AND I
WON'T GO TO THE ADDITIONAL
TREATMENT DEVELOPED BUT YOU CAN
ASK ABOUT IT.
HERE'S THE RESULT FOR THE
RECONSTRUCTION OF THE NETWORK
FROM BREAST CANCER.
S THIS OF THIS IS FOCUSSED ON
THE MUTATIONAL SIGNATURE AND THE
GENES DIRECTING ADDED INTO OR
OUT OF THE SIGNATURES AND
THERE'S AN INFORMATION WE CAN
INFER FROM THAT AND WE FOCUS DID
WE EXPLAIN OPTIMIZATION AND
SIGNATURES AND WE DID.
AND WHEN WE LOOK AT THE
SIGNATURE WE COULD SEE THE DOWN
REGULATION OF GENES ARE IN THE
REPAIR PATHWAYS.
THERE'S ONE INTRIGUING QUESTION
THERE'S A MODEL OF THE SIGNATURE
ESPECIALLY WITH THE MUTATION.
WE COULD INFER THAT THIS IS A
COMBINATION WHICH IS A PRIMARY
SOURCE OF THE SIGNATURE IN
BREAST CANCER AND IT'S ATTACKING
THE SINGLE STRANDED DNA SO WE
HAVE A NEW METHOD AND TESTED
PREVIOUS METHODS FOR THE TASK
AND ALSO THE PARTICULAR
SUGGESTION WAS THE SIGNATURE AND
THERE ARE OTHER QUESTIONS AS WE
WOULD LIKE TO ANSWER.
ONE IS THIS AS WE WORK IN THE
AREA WE REALIZE THERE ARE CASES
THAT EITHER DE NOVO APPROACH IS
GOOD.
WE SUSPECT IT MAY CON TOWN A NEW
SIGNATURE BUT THE SIZE OF THE
DATA SET IS NOT BIG ENOUGH TO
UNLEASH DE NOVO SIGNATURE
DISCOVERY.
WORKING ON THE COMBINED APPROACH
WE CAN TAKE THE BENEFIT OF BOTH
AND BEING ABLE TO ADDRESS THE
NOVEL SIGNATURE EVEN WHEN THE
DATA SET'S NOT HERE.
THE SECOND THING SHE'S WORKING
ON IS TO LEVERAGE THE MODELS TO
START THE MUTATION SIGNATURE AND
OTHER APPROACHES AND IN
COLLABORATION WITH THE LAB.
NOW I'D LIKE TO MOVE TO THE
SECOND ASPECT OF OUR STUDIES
RELATED TOE TUMOR EVOLUTION
WHICH IS WHAT IS THE RELATION OF
THE TUMOR AND ENVIRONMENT.
AND THE FIRST THE RELATIONSHIP
TO THE GREEN ADJACENT IS AND
THERE'S A TUMOR ALTERATION TO
THE ADJACENT TISSUE CAN
CONTRIBUTE TO CANCER.
AND WE STARTED THIS TISSUE IN
THE CONTEXT OF IMPACT OF SMOKING
AND CAN SEE IT HAS CAUSED THIS
TISSUE.
AND THE QUESTION IS WHAT IS THE
RELATIONSHIP AND WHAT CAUSES THE
DIVISION OF THE ASSUMPTION THAT
THE NORMAL TISSUE IS CLOSER TO
TUMOR EXPECTED BY CHANCE?
IN TRYING TO ADDRESS THE SOURCE
OF THE RELATIONSHIP AGAIN THIS
IS REALLY IF TISSUE HAS CANCER
PROGRESSION WE SHOULD BE ABLE TO
PREDICT THE EXPRESSION OF TUMOR
GENES FROM THE EXPRESSION OF THE
GENES IN THIS NORMAL TISSUE OR
CONTROL SAMPLE.
HE OPTIMALIZED THE PREDICTIVE
POWER TO PREDICT THE GENES IN
THE TUMOR.
WE DIDN'T ATTEMPT TO PREDICT ALL
JUST THOSE DIFFERENTIALLY
EXPRESSED IN TUMOR AND NORMAL.
NOT ALL COULD BE PREDICTED.
NOT ALL THE GENES IN THE TISSUE
WERE AND ALLOWED US TO
UNDERSTAND WHO IS PREDICTING AND
THE GENES THAT PREDICTING CELL
TO CELL SIGNALLING AND
SIGNALLING AND OTHER ARE RELATED
TO RESPONSE OF ENVIRONMENT.
IT LED US TO CONCLUDE THE
RELATIONSHIP OF THOSE TISSUE ARE
MOSTLY DUE IT THE FACT THEY'RE
EXPOSED TO THE SAME ENVIRONMENT
AND SOME IS ALSO TUMOR
ENVIRONMENT THAT IS BEING
CREATED BY TUMOR.
WE HAVE A NEW METHOD ASSIGNMENT
PREDICTION SUGGESTED CUT TO THE
CASE THE IMPACT OF THE
ENVIRONMENT AND INTERESTINGLY
MANY OF THOSE PREDICTION WE HAD
KNOWN TO BE MARKERS OF TUMOR
PROGRESSION WHICH IS REALLY
INTERESTING TO SEE YOU CAN SEE
THE MARKERS OF TUMOR PROGRESSION
ALREADY IN THE ADDITIONAL NORMAL
TISSUE.
I'LL MOVE RELATED TO THE
RELATIONSHIP BETWEEN TUMOR
ENVIRONMENT.
OBVIOUSLY TODAY IN ONE OF OUR
IMPORTANT APPROACHES TO THE
TUMOR ENVIRONMENT IS TO LOOK AT
TRANSCRIPTOMIC AND WHAT I MEANT
TO SAY AT THE BEGINNING WHEN I
SWITCH TO GREEN IT'S A PROJECT
AND SOME IS FUTURE WORK.
HERE IS WORK STARTED BY THIS
QUESTION OF THE RELATIONSHIP
BETWEEN TUMOR AND ENVIRONMENT.
I WOULD LIKE TO BRIEFLY
SUMMARIZE THE TECHNOLOGY.
THIS IS A NEW TECHNOLOGY THAT
STARTS WITH A SLICE OF TISSUE
AND THEN IN THE SO-CALLED SPOTS
THAT CONTAIN ONE TO 10 CELLS
THEY'RE BEING SEQUENCED AND
INFORMATION ABOUT EACH FROM
WHICH IT IS PRESERVED.
MUCH OF THE WORK WAS RELATED TO
THE DATA AND TRYING TO
UNDERSTAND WHAT TYPE OF CELLS
ARE THERE AND TRYING TO SEE
WHICH CELLS ARE FOR WHICH ONE
AND HOW TO INTERPRET THE
RELATION.
HERE WE'D LIKE TO ASSIGN A
PHENOTYPE TO THOSE SPATIAL
REGIONS BUT THE MAIN IDEA IS IS
FOCUSSING ON THE
GCDA DATA AND TO INFER SPECIAL
TRANSCRIPTOMIC IS BASED ON THE
DATA THE PATIENT IS OBTAINED
WHERE WE KNOW THE PHENOTYPE AND
THAT COULD BE SURVIVAL TIME,
THAT COULD BE TUMOR PURITY, IT
COULD BE ANOTHER PHENOTYPE
AVAILABLE OR BEING THE TYPE OF
PHENOTYPE WE TRY TO TRANSFER TO
THE SPATIAL DATA.
USING THE REGRESSION MODEL WE
OBTAINED THE SO-CALLED EIGEN
PATIENT AND WE HAVE THE GENE AND
IT'S OUR LINK TO THE SPATIAL
DATA AND THE CORRELATION OF THE
EIGEN GENE TELLS US HOW IT'S
RELATED TO THE PHENOTYPE OF
INTEREST.
IS THAT WORK BEING?
THERE'S TWO EXAMPLES.
THEY OVERLAP NOT PERFECTLY BUT
HOWEVER WHEN WE WORK AS
PATHOLOGISTS WE UNDERSTAND THE
PATHOLOGICAL ANNOTATION OF THE
SLIDE AND TWO GROUPS OF CLUSTERS
OF THE CANCER-RELATED SPATIAL
LOCATION.
ONE RELATED TO IN SITU AND
NONINVASIVE.
AND LOOKING BACK TO THE TISSUE
WE IDENTIFY A CASE WHERE WE HAVE
THIS TUMOR ADJACENT TISSUE HERE
THIS IS AGAIN THE EXPLANATION
FROM THE PATHOLOGY UNIT THAT
HELP US INTERPRET THE DATA.
THE DATA SHOWS WE HAVE THIS AND
AS EXPLAINED WHAT WE SEE HERE IS
INDEED CELLS THAT DO MULTIPLY
AND EVERYTHING ABOUT THE CELLS
IS NORMAL IN TERMS OF HOW THEY
LOOK.
AND WE'RE STILL WORKING ON THAT
AND BY FOCUSSING ON THE
PHENOTYPE IT'S THE OPTIMAL
APPROACH AS PROPOSED BY OTHERS
AND IMPORTANT IS THE METHOD
SHOWS IT'S IMPORTANT TO LOOK AT
THE INTERACTION OF MANY
PHENOTYPES TO HAVE A HOLISTIC
VIEW AND TRANSFORM OTHER DATA
TYPES BETWEEN EACH OTHER AND
ALSO FOCUS ON THE ASSIGNMENT OF
THE PHENOTYPE TO LARGER AND
LARGER REGIONS.
FINALLY, LET ME BRIEFLY MENTION
ANOTHER VERY INTERESTING WORK
THAT WE UNDERTAKE WAS TO
UNDERSTAND THE EVOLUTION.
SO ALL THIS COMES AND THEY DO
EXIST AND THEY COMPETE AND HAVE
STRATEGIES OF ADAPTATION TO TAKE
ADVANTAGE AND OUR QUESTION WAS
DO THE DIFFERENT HAVE THE SAME
ADAPTATION OR DIFFERENT AND IS
THE ASSUMPTION USEFUL FROM THE
MEDICAL POINT OF VIEW WE CAN
LEARN ABOUT IT.
WE DECIDED TO LOOK AT THE
ADAPTATION FROM THE PERSPECTIVE
OF ADAPTATION OF GREEN
EXPRESSION.
WE NOTE THE GENE EXPRESSION
BECAUSE THEY CAN BE TREATED BUT
NEVERTHELESS THEY'LL INFLUENCE
GENE EXPRESSION AND FOR US WHEN
WITH HE SEE WHICH GENES ARE
BEING SELECTED FOR IT'S EASIER
TO INTERPRET WHEN LOOKING AT
WHAT IS AFFECTED.
AND ONE THE MODELLING OF
EVOLUTION OF SEQUENCE AND WE
LOOK AT THE MODELLING AND
EVOLUTION IS CHARACTERIZED BY
THE BROWNIAN MOTION AND THE
ADAPTIVE IS MOLTEDDELLED AND BEE
IT WILL BE IN THE POSTER I'LL
SKIP TO THE NEXT SLIDE AND
PREVIOU
PREVIOUSLY THEY DEVELOPED A
MODEL TO INFER THE MODEL FOR
GENE EXPRESSION EVOLUTION.
HIS INTEREST WAS ADAPTATION TO
DIET IN FLIGHT.
WE WERE INTERESTED WHETHER WE
CAN REALLY APPLY THE METHOD TO
TUMOR EVOLUTION AND ASKED OUR
FRIENDS IN CANCER INSTITUTE AND
FOUND A GROUP THAT HAD THE DATA
THAT WE NEED.
AGAIN, I HOPE GENE WILL TELL YOU
MORE ABOUT IT.
WHAT WE LEARN FROM APPLYING THIS
MODELLING TO UNDERSTAND THE
ADAPTATION OF GENE EXPRESSION IS
TWO MODES OF ONLY TO EXPRESSION
IN MELANOMA.
ONE IS ONE WE SEE INVESTMENT AND
THERE'S A SELECTION TO RIBOSOME
AND THINK THEY'RE RELATED AND
THERE WAS A SELECTION FOR
SIGNALLING AND WHEN TESTED THEY
TEND TO BE IMMUNOTHERAPY
SENSITIVE AND THEY TEND TO HAVE
THERAPY RESISTANT.
TO THE BEST OF OUR KNOWLEDGE
IT'S THE REGULAR STUDY OF GENE
EXPRESSION INTO EVOLUTION.
AND THE OBSERVATION WE OBTAINED
TO THE QUESTION IS YOU HAVE TWO
GROUPS OF BASIC TYPES THAT HAVE
DIFFERENT MODES OF ADAPTATION.
WHAT WILL HAPPEN AND HOW DO THEY
COMPETE?
SO OUR EXPERIMENTAL
COLLABORATORS SENT AN EXPERIMENT
AND THE LINES GENERATE THEM INTO
MOUSE WITH DIFFERENT PROPORTION
AND WE UNDERSTAND THE DYNAMICS
OF THIS EVOLUTION FOR
COMPETITION USING THERAPY AND
HERE IT'S HELPED BY A TALENTED
UNDERGRADUATE.
WHY IT'S IMPORTANT IS WE CAN
CONT
CONTROL.
AND IF YOU HAVE THIS TUMOR THAN
IT'S IMPORTANT THIS CAN PROVIDE
SOME INFORMATION OF THE PROGRESS
AND WE CAN KEEP THE CONTROL AND
THAT'S OUR RESEARCH AND I'M
RUNNING OUT OF TIME AND I WANTED
TO MENTION THERE'S OTHER IN THE
GROUP I COULDN'T DISCUSS BUT
WANT TO MENTION THE WORK WE HAVE
UNDERTAKEN FOR MANY YEARS NOW TO
STUDY THE AUTOMATIC STRUCTURES
OF DNA.
THIS IS COMBINED WORK OF
EXPERIMENTAL AND COMPUTATIONAL
GROUPS WHERE THEY ARE HAVE
COMPUTATIONAL APPROACHES AND
DOWN TO THE WIRE OF THE SIGNAL
TO HARVEST THIS AND WORKED ON
THIS DATA AND THE WORK OF ERMIN
AND HE'LL TELL YOU ABOUT IT AND
TOGETHER WE WORKED ON THE
REFINEMENT OF A QUESTION RELATED
TO SINGLE CELL DATA IN TUMOR AND
JOHN IS LINKING THE WORK.
WE'VE ALSO BEEN INVOLVED FOR
MANY YEARS IN THE FLY CELL ATLAS
WITH WORK AND MOSTLY WORK OF
SOUMITRA PAL AND FINALLY THIS IS
WORK FROM NETREX-CF BY A FORMER
MEMBER OF MY GROUP NOW AT
INDIANA UNIVERSITY.
YOU'VE SEEN THE FACES AS I WAS
DISCUSSING THE RESEARCH AND
MENTIONED THE COLLABORATORS
BECAUSE IT'S CRUCIAL AND OUR
COLLABORATOR ON SINGLE CELL AND
THIS IS WORK ON TUMOR EVOLUTION
AND HELPS IN MANY WAYS WHEN WE
NEED TO DO EXPERIMENTS AND HE'S
ALWAYS OPEN TO PROVIDING INSIGHT
AND WE HAVE A PATHOLOGIST WHO
HELPS US ANNOTATE THE SLIDE IN
THE CASES WHERE THEY ARE HAVEN'T
BEEN AND THESE HELPFUL IN THE
PRODUCT AND I MENTIONED HIM AND
WE HAVE A PROFESSOR AT
UNIVERSITY AND CONTINUES THE
WORK OF MUTATION OF G1 AND
PROFESSOR WANG FROM INDIANA
UNIVERSITY AND MATHEMATICAL
MODELLING COMBINED WITH MACHINE
LEARNING THAT WAS HIS IDEA.
AND WITH THAT, THANK YOU ALL AND
I'LL ASK IF THERE'S ANY QUESTION
AND MAYBE I'LL JUST PAUSE FOR
QUESTIONS AS YOU REMEMBER WHAT I
TALKED ABOUT.
THANK YOU.
6:
>> THANK YOU VERY MUCH.>> THANK.
I'LL TURN IT OVER.
LOOKS LIKE YOU'RE TALKING BUT
WE'RE NOT HEARING.
>> GO AHEAD ONE YOUR QUESTION.
>> EXCELLENT PRESENTATION.
REALLY MOVING FORWARD ONE WILL
ALL THE NEW TECHNOLOGY AND SUCH
AND KEEPING UP WITH THE
EXPERIMENTAL AND COMPUTATIONAL
IS A CHALLENGE IN OUR FIELD AND
YOU'RE DOING A GREAT JOB.
I WAS WONDERING, THIS MAY BE A
NAIVE QUESTION BUT WHEN YOU
STUDY MUTAGENIC AND MAYBE ALIE
TO OTHER SIGNATURES, DO YOU CARE
ABOUT THE PATIENT HAVING HAD ANY
PARTICULAR TREATMENT?
LIKE, ANY CHEMO THERAPY OR ANY
OF THE OTHER TREATMENTS
INFLUENCE IN ANY WAY YOUR
ANALYSIS AND HOW DO YOU DEAL
WITH THAT?
>> TREATMENT CAN INFLUENCE A
PATIENT.
OFTEN TREATMENT IS ALSO
INTRODUCING MUTATIONS.
IN THESE CASES WIRE ABLE TO PICK
UP A SPECIFIC TREATMENT RELATION
SIGNATURE.
WE KNOW BECAUSE IF WE SEE THE
SIGNATURE APPEARS IN A PATIENT
AND WE ASSUME THIS IS BECAUSE OF
TREATMENT.
AND ONE CAN PERFORM EXPERIMENTAL
CONFIRMENT AND WHEN THERE'S
NOVEL SIGNATURE THERE'S ALSO A
QUESTION, IS THERE ANYTHING IN
THE ENVIRONMENT PATIENTS WE
ANALYZE THAT MAY BE TRIGGERING
THIS SIGNATURE.
THIS IS BOTH.
SOMETIMES IT'S OBVIOUS.
SOMETIMES WHEN WE SEE THE COHORT
MAY BE IT'S A FACTOR TO BE
CONSIDERED OR IS THERE SOMETHING
THAT THE COHORT WAS EXPOSED AND
WE HAVE BEEN HOPE TO WORK WITH A
NOVEL COHORT BUT THERE'S
EXAMPLES OF THIS TYPE OF
INFERENCE.
>> THANK YOU, TERESA.
>> WHAT TO YOU MEAN BY
ENVIRONMENT?
>> ENVIRONMENT IN PLACES AND
THIS PLAY INFLUENCE THE TISSUE
EXPOSED TO SMOKING BUT ALSO THE
TUMOR ENVIRONMENT.
THAT'S PART OF THE ENVIRONMENT
TO WHAT'S HAPPENING IN TUMOR
ADJACENT MUTATION.
>> IN THIS CASE IT'S CAUSAL AND
NEIGHBORS?
>> AND HARDER TO SAY TO
ESTABLISH CAUSALITY BASED ON THE
KNOWLEDGE IT'S TUMOR THAT
GENERATES THE INTERESTING
ENVIRONMENT NOT THE NORMAL.
>> THERE'S AN IMPACT BUT HOW DO
YOU INTERPRET THE PATIENT AND
EIGEN GENE.
>> WE MODELIZE FROM THE DEAN
EXPRESSION OF THE PHENOTYPE AND
THAT PREDICTION IS SUMMARIZED AS
ONE NUMBER AND THE EIGEN GENE
YOU CAN COMPUTE AND HAVE THE
PROTECTION OF THE PHENOTYPE AND
FOR THE TRANSCRIPTOMIC AND I
THINK THIS IS AGAIN LIKE LET'S
TRANSFORM THE EIGEN GENE TO
EIGEN PATIENT.
AND AROUND GENE EXPRESSION AND
THE GENE EXPRESSIONS OPTIMALIZED
TO THE PHENOTYPE AND NOW WE USE
THE EIGEN PATIENT TO COMPUTE
WITH EXPRESSION IN SINGLE SPOT.
SO AND THERE MAY BE OTHER CASES
WHERE WE HAVE A MEASURE IN ONE
SETTING AND USE THE EIGEN
PATIENT AS A VEHICLE TO
TRANSLATE WHEN YOU HAVE GENE
EXPRESSION.
>> VERY NICE TALK BUT A LOT OF
INFORMATION.
THANK YOU.
>> I HAVE A QUESTION.
>> GO FOR IT.
>> I ALSO WANT TO THANK YOU
TERESA FOR A LUCID TALK AND I
AGREE IT WAS FUN TRYING TO KEEP
UP.
PICKING UN UP ON THE ENVIRONMENT
AND YOU ALLUDED TO VIOLATIONS OF
ADAPTIVITY AND MENTIONED BREAST
CANCER BUT WONDER IF YOU DO PAN
CANCER ANALYSIS AND PARTICULARLY
DO YOU SEE CANCER SPECIFIC
EFFECTS OF EXPOSURES ON MUTATION
SIGNATURES?
IN OTHER WORDS, ARE THERE
EXPOSURE BY CANCER INTERACTIONS?
>> OTHER PEOPLE LOOKED AT THOSE
AND THERE'S A CHANCE TO PREDICT
CANCERS BASED ON THE EXPOSURES.
ON AVERAGE A TUMOR TYPE HAS FIVE
AND BREAST CANCER HAS 15
DIFFERENT SIGNATURES AND RELATED
TO OTHERS BUT IT'S NOT EVERY
CANCER HAS THE POSSIBLE
SIGNATURE.
THERE'S SELECTIVITY.
AND ALSO AND THE ENVIRONMENT
INCLUDED IMMUNE RESPONSE AND
WHICH SIGNATURE COULD BE
TRIGGERED AND WE LEVERAGE THE
METHOD THAT COMBINES BOTH
BECAUSE WE KNOW SIGNATURES WILL
BE IN EVERY CANCER AND WE START
THERE.
SIGNATURE NUMBER 1 IS RELATED TO
RELATED TO TYPICAL STANDARD DNA
REPLICATION MECHANISM AND
THERE'S TRADITIONALLY SIGNATURE
ONE IS RELATED BECAUSE THEY
DEPEND LOU THEY ARE REPAIRED BUT
WHEN YOU HAVE TRANSLATION YOU
HAVE THE DNA AND THE PARTICLE
SNEAKS IN LATER IN THE
REPLICATION AND SOME ARE GENETIC
AND ACROSS MANY CANCER TYPE AND
SOME ARE CANCER TYPE SPECIFIC
BUT YOU HAVE COMBINATION AND
THERE'S CHARACTERISTIC OF BREAST
CANCER AND OVARIAN CANCER AND WE
SEE IT IN THE PROSTATE CANCER
AND MAYBE SOME OTHERS BUT I AM
NOT AWARE OF ALL OF THEM AND
THIS IS PREDICTIVE RESPONSE TO
PRP INHIBITER SO THERE'S A
MIXTURE.
SOME ARE UNIQUE.
WE DON'T SEE THIS ELSEWHERE.
>> THANK YOU.
FOR THE SAME ALGORITHM YOU
TALKED ABOUT THE DE NOVO
SIGNATURE DATA.
I WASN'T CLEAR IF YOU DO YOUR
OWN VARIANT CALLING BUT IF YOU
DO I WONDER IF YOU ANTICIPATE
ANY IMPACT OR CHALLENGES OF THE
DEVELOPMENT IN THE EMERGENCE OF
PANGENOME REFERENCES STRUCTURES
OPPOSED TO THE TRADITIONAL
RELIANCE ON A SINGLE REFERENCE
GENOME?
>> AH, UNONE WAY THIS IS ALSO A
CHALLENGE IN THE OPPORTUNITY
END.
IF YOU HAVE CANCER GENOME
SUBJECT TO THE COPY NUMBER AND
IN SOME WAY YOU MAY THINK IT'S
DIFFICULT TO ASSIGN THEM TO
PROPER PLACES BUT IF WE HAD
UNDERSTANDING THE WHOLE
CHROMOSOME HAVE CHANGED THEN WE
CAN USE IT AS TIMING AND SEE THE
MUTATIONS BEFORE AND AFTER AND
IT'S A POWERFUL WAY TO
UNDERSTAND THE DYNAMICS OF THE
SIGNATURE AND SEEING THE
SIGNATURE AS THEY ARE ARE, WE
DECENT HAVE THE TIME SCALE.
IF WE UNDERSTAND THEM WE CAN USE
THEM TO DO THE TIMING OF THE
SIGNATURE AND IF WE LOOK AT THE
INTERACTION BETWEEN SIGNATURES
AND YOU HAVE TWO THAT GENERATE A
LOT OF MUTATION AND THEY BOTH
HAVE SIGNATURE WE HAVE TO BE
ABLE TO ANALYZE TO SEE WHICH WAS
FIRST AND SECOND BY MODELLING
THE EVENT WHEN THEY ARE START TO
INTERACT.
>> THANK YOU.
>> DOES IT ANSWER THE QUESTION?
>> IT DOES.
IT'S A CHALLENGE AND OPPORTUNITY
AND WE'RE ALSO TRYING TO WRAP
OUR HEAD AROUND HOW IT MIGHT
AFFECT OUR WORK SO, YEAH.
>> SO WE'RE AT THE TIME TO HAVE
A CLOSED SESSION WITH THE
POSTDOCTORAL TRAINEE
PRESENTATIONS