S T ABL E OF CONT E NT AGE NDA DAY 1 DAY 2 GOAL S OF GE - - PDF document

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Ge no mic Me dic ine VIII: NHGRIs Ge no mic Me dic ine Po r tfo lio S T ABL E OF CONT E NT AGE NDA DAY 1 DAY 2 GOAL S OF GE NOMIC ME DICINE VIII ME E T ING OBJE CT IVE S RE L T AE D T O GE NOMIC ME DICINE

SLIDE 1

SLIDE 2

Ge no mic Me dic ine VIII: NHGRI’s Ge no mic Me dic ine Po r tfo lio T ABL E OF CONT E NT S

AGE NDA DAY 1 DAY 2 GOAL S OF GE NOMIC ME DICINE VIII ME E T ING OBJE CT IVE S RE L T AE D T O GE NOMIC ME DICINE PROGRAMS BARRIE RS T O GE NOMIC ME DICINE PROGRAMS IMPACT F UL PUBL ICAT IONS F OCUS PROGRAM SUMMARIE S

Clinic al Ge nomic s Re sour

c e (ClinGe n) inc luding NCBI’s ClinVar

Clinic al Se que nc ing E

xplor ator y Re se ar c h (CSE R) inc luding intr amur al ClinSe q

le c tr

nic Me dic al Re c or

ds and Ge nomic s Ne twor k (e ME RGE )

Ge nomic Me dic ine Me e tings Pr
gr

am as a whole (GM MT GS)

Global Ge nomic Me dic ine Collabor

ative (G2MC)

Imple me nting Ge nomic s into Pr

ac tic e (IGNIT E )

Ne wbor

n Se que nc ing in Ge nomic Me dic ine and Public He alth (NSIGHT )

Undiagnose d Dise ase s Ne twor

k (UDN) RE L AT E D PROGRAM SUMMARIE S

CMG
CPIC
E

NCODE

GAPH
GA4GH
GGR
GS- IT
GT

E x

H3AF

RICA

HMORN
IOM
L

SAC

ISCC
MVP
NCI- AL

CHE MIST

NCI- MAT

PAGE
PCORne t
PGRN
Phe nX
PMI

HOT E L AND T RAVE L L OGIST ICS INF ORMAT ION GE NOMIC ME DICINE VIII ME E T ING – CONT ACT L IST S

SLIDE 3

Ge no mic Me dic ine VIII: NHGRI’s Ge no mic Me dic ine Po r tfo lio

June 8- 9, 2015 Hilton - Washington DC / Roc kville 1750 Roc kville Pike , Roc kville , MD 20852 (301) 468- 1100

Monday, June 8th L OCAT ION: Hilton – Washington DC / R

c kville Hote l

WE BCAST : Ge nome T V - http:/ / www.ge no me .go v/ Ge no me T V/ T WIT T E R: #Ge nomic Me d8

7:30 AM Re g istra tio n a nd Bre a kfa st Re g istra tio n T a b le 8:30 AM We lc o me , I ntro d uc tio ns, a nd Go a ls o f the Me e ting Ho wa rd Mc L e o d E ric Gre e n 8:45 AM Ove rvie w o f NHGRI Ge no mic Me d ic ine Pro g ra ms T e ri Ma no lio 9:15 AM

PANE L 1: K

e y Una d d re sse d E vid e nc e Ga ps in Ge o ff Ginsb urg * I mple me nting Ge no mic Me d ic ine Jo na tha n Be rg Pie rre Me ulie n Gurva ne e t Ra nd ha wa 10:15 AM BRE AK 10:45 AM

PANE L 2: Co nsiste nc y o f Inte rpre ta tio n o f Va ria nts Ac ro ss

Da n Ro d e n* E xpe rt L a b s / Gro ups, ClinVa r Sub missio ns? Ga il Ja rvik Ro b e rt Gre e n 11:45 AM

PANE L 3: Cha ng e s in E

vid e nc e a nd T hus Upd a ting Ho wa rd Ja c o b * Re c o mme nd a tio ns, T re a tme nt He id i Re hm Sha ro n Plo n K a trina Go d d a rd 12:45 PM Wo rking L unc h 1:30 PM

PANE L 4: Me tric s o f Pro g re ss a nd Me a sure s o f I

mpa c t Ma rc Williams* I nc lud ing Co st-E ffe c tive ne ss, Outc o me s to Va lue to Pa ye rs, Wa rwic k And e rso n I nflue nc ing Quality o f Ca re T hro ug h L e a rning He a lthc a re E rwin Bo tting e r Syste ms Ruth Bre nne r 3

SLIDE 4

Ge no mic Me dic ine VIII: NHGRI’s Ge no mic Me dic ine Po r tfo lio

June 8- 9, 2015 Hilton - Washington DC / Roc kville 1750 Roc kville Pike , Roc kville , MD 20852 (301) 468- 1100

Monday, June 8th (Continue d) L OCAT ION: Hilton – Washington DC / R

c kville Hote l

WE BCAST : Ge nome T V - http:/ / www.ge no me .go v/ Ge no me T V/ T WIT T E R: #Ge nomic Me d8

2:30 PM

PANE L 5: E

nha nc ing F unc tio na lity o f E HRs fo r Ge no mic Re x Chisho lm* Re se a rc h, Inc lud ing E

Phe no tying , Inte g ra ting Ge no mic

Ale xa Mc Cra y Da ta , T ra nsp o rta b le CDS, Priva c y T hre a ts Chris Chute 3:30 PM BRE AK 4:00 PM

PANE L 6: I

nc re a sing Dive rsity Amo ng Pa tie nt Po pula tio ns Ca ro l Bult* a nd Ca re Syste ms Cynthia Po we ll Ve nc e Bo nha m Cra ig Ha nis 5:00 PM F irst Da y Summa ry a nd Disc ussio n T e ri Ma no lio Ho wa rd Mc L e o d 6:00 PM

ADJOURN

All Atte nd e e s – On yo ur o wn fo r d inne r
Ge no mic Me d ic ine Wo rking Gro up ONL

Y - Se e yo ur e ma il ab o ut e ve ning d e ta ils 4

SLIDE 5

Ge no mic Me dic ine VIII: NHGRI’s Ge no mic Me dic ine Po r tfo lio

June 8- 9, 2015 Hilton - Washington DC / Roc kville 1750 Roc kville Pike , Roc kville , MD 20852 (301) 468- 1100

T ue sday, June 9th L OCAT ION: WE BCAST : T WIT T E R: Hilton – Washington DC / Roc kville Hote l Ge nome T V - http://www.genome.gov/GenomeTV/ #Ge nomic Me d8

7:30 AM Bre a kfa st 8:30 AM F irst Da y Re c a p Ho wa rd Mc L e o d T e ri Ma no lio 8:45AM

PANE L 7: Stre a mlining Clinic al Wo rkflo w, T

ra nspo rta b ility Ho wa rd Mc L e o d * to Othe r Syste ms, ClinVa r Sub missio ns? Mike Ga zia no Ste phe n K ing smo re E rin Ramo s 9:45 AM

PANE L 8: Clinic ia n E

d uc a tio n (E spe c ia lly Re sid e nts Ma ry Re lling *

n Ro ta tio n, Ge ne tic Co unse lo rs), Re po rting Re sults to

Julie Jo hnso n Clinic ia ns Bo b Wild in We nd y Rub inste in 10:45 AM BRE AK 11:15 AM

PANE L 9: Pa tie nt-F

a c ing Info rma tio n T

o ls,

Co unse ling / Co nse nt, Re p o rting Re sults to Pa tie nts L a ura Ro drig ue z* Ste ve Jo ffe Ja ne t Willia ms

William Lawrence

12:15 PM WORK ING L UNCH 12:45 PM Se c o nd Da y Summa ry a nd Disc ussio n Ho wa rd Mc L e o d T e ri Ma no lio 1:30 PM Ne xt Ste ps T e ri Ma no lio Ho wa rd Mc L e o d 2:30 PM

ADJOURN

SLIDE 6

Ge no mic Me dic ine VIII: NHGRI’s Ge no mic Me dic ine

Po rtfo lio

Glossar y of Abbr e viations

AF MSA – Air F

rc e Me dic a l Se rvic e s Ag e nc y

ClinGe n – Clinic a l Ge no mic s Re so urc e CMG – Ce nte rs fo r Me nde lia n Ge ne tic s CPIC – Clinic a l Pha rma c o g e ne tic s I

mple me nta tio n Co nso rtium

CSE R – Clinic a l Se q ue nc ing E

xplo ra to ry Re se a rc h

e ME R GE Ne twor k – E

le c tro nic Me dic a l Re c o rds a nd Ge no mic s Ne two rk

E NCODE – E

nc yc lo pe dia o f DNA e le me nts

G2MC – Glo b a l Ge no mic Me dic ine Co lla b o ra tive GA4GH – Glo b a l Allia nc e fo r Ge no mic s a nd He a lth GAPH – Ge no me Ca na da / Ca na dia n I

nstitute s o f He a lth Re se a rc h Ge no mic s a nd Pe rso na lize d He a lth

GGR – Ge no mic s o f Ge ne Re g ula tio n GS- IT – Ge no me Se q ue nc ing I

nfo rma tic s T

o ls

GT E x – Ge no type T

issue E xpre ssio n Pro je c t

H3Afr ic a – Huma n He a lth a nd He re dity in Afric a HMOR N – He a lth Ma inte na nc e Org a niza tio n Re se a rc h Ne two rk IGNIT E – Imple me nting Ge no mic s into Pra c tic e IOM – I

nstitute o f Me dic ine

ISCC – I

nte r-So c ie ty Co o rdina ting Co mmitte e fo r Pra c titio ne r E duc a tio n in Ge no mic s

L SAC – L

a rg e -Sc a le Ge no me Se q ue nc ing a nd Ana lysis Ce nte rs pro g ra m

MVP – Millio n Ve te ra ns’ Pro g ra m NCI- AL CHE MIST – Adjuva nt L

ung Ca nc e r E nric hme nt Ma rke r I de ntific a tio n a nd Se q ue nc ing T ria ls, g e ne tic a lly dire c te d Na tio na l Ca nc e r I nstitute tria l

NCI- MAT CH – Mo le c ula r Ana lysis fo r T

he ra py Cho ic e , g e ne tic a lly dire c te d Na tio na l Ca nc e r Institute tria l

NHGR I GMWG- NHGRI Ge no mic Me dic ine Wo rking Gro up NSIGHT

– Ne wb o rn Se q ue nc ing in Ge no mic Me dic ine a nd Pub lic He a lth

PAGE – Po pula tio n Arc hite c ture using Ge no mic s a nd E

pide mio lo g y

PCOR ne t – Pa tie nt-Ce nte re d Outc o me s Re se a rc h Ne two rk PGR N – Pha rma c o g e ne tic s Re se a rc h Ne two rk Phe nX – Phe no type s a nd E

xpo sure s T

o lkit

PMI – Pre c isio n Me dic ine Initia tive UDN – Undia g no se d Dise a se s Ne two rk USAF – U.S. Air F

rc e

SLIDE 7

Go als and Pr

ams

T he Ge no mic Me dic ine Wo rking Gro up c o nve ne s its ne xt me e ting in the GM se rie s, G M VI I I : “NHGRI ’ s Ge no mic Me dic ine Pro g ra ms.” GM VI I I ha s a sse mb le d le a de rship fro m NHGRI g e no mic me dic ine pro g ra ms a nd re pre se nta tive s fro m o the r NI H I Cs a nd e xte rna l g ro ups to e xa mine the NHGRI g e no mic me dic ine po rtfo lio in lig ht o f e vo lving sc ie ntific kno wle dg e a nd

ppo rtunitie s.

Ob je c tive s fo r GM VI I I a re to :

1. Re vie w NHGRI

’ s o ng o ing g e no mic me dic ine po rtfo lio a nd ide ntify g a ps a nd o ppo rtunitie s fo r c o lla b o ra tio ns a mo ng the se pro g ra ms

2. I

de ntify re la te d pro g ra ms o f o the r NIH I nstitute s/ Ce nte rs o r o the r fund e rs a nd o ppo rtunitie s fo r c o lla b o ra tio ns with NHGRI pro g ra ms

3. I

de ntify re se a rc h ne e d s in g e no mic me d ic ine fo r NHGRI a nd pa rtne r fe d e ra l a g e nc ie s to pursue

4. E

nha nc e a ppro a c he s to c a p turing a nd d isse mina ting b e st p ra c tic e s fo r g e no mic me d ic ine

5. E

xa mine po te ntia l me tho d s fo r a sse ssing impa c t o f pro g ra ms F

c us Pro g ra ms to b e a d d re sse d d ire c tly in the a g e nd a inc lude :
Clinic al Ge no mic s Re so urc e (ClinGe n) inc lud ing NCBI

's ClinVa r

Clinic al Se q ue nc ing E

xplo ra to ry Re se a rc h (CSE R) inc lud ing intra mural ClinSe q

le c tro nic Me d ic al Re c o rd s a nd Ge no mic s Ne two rk (e ME RGE )

Ge no mic Me d ic ine Me e ting s pro g ra m a s a who le
Glo b al Ge no mic Me d ic ine Co lla b o ra tive (G2MC)
I

mple me nting Ge no mic s into Pra c tic e (I GNIT E )

Ne wb o rn Se q ue nc ing in Ge no mic Me d ic ine a nd Public He alth (NSIGHT

)

Und ia g no se d Dise a se s Ne two rk (UDN)

Re la te d Pro g ra ms to info rm the d isc ussio n, b ut no t e xa mine in d e p th, inc lud e :

Big Da ta to K

no wle dg e (BD2K) c linic al sub se t

Clinic al Pha rma c o g e ne tic s I

mple me nta tio n Co nso rtium (CPIC)

nc yc lo pe d ia o f DNA e le me nts (E NCODE )

Ge ne tic a lly d ire c te d NCI

tria ls inc lud ing MAT CH a nd AL CHE MI ST

Ge no type T

issue E xpre ssio n Pro je c t (GT E x)

Ge no me Se q ue nc ing Info rma tic s T
o ls (GS-IT

)

Ge no me Ca na d a / CI

HR Ge no mic s a nd Pe rso na lize d He alth (GAPH)

Ge no mic s o f Ge ne Re g ula tio n (GGR)
Glo b al Allia nc e fo r Ge no mic s a nd He alth (GA4GH)
Huma n He alth a nd He re d ity in Afric a (H3Afric a )
HMO Re se a rc h Ne two rk (HMORN) inc lud ing HMO Co lla b o ra to ry
I

nstitute o f Me d ic ine (IOM) Ge no mic s Ro und ta b le inc lud ing E MR Ac tio n Co lla b o ra tive

nte r-So c ie ty Co o rd ina ting Co mmitte e fo r Pra c titio ne r E d uc a tio n in Ge no mic s (I SCC)

a rg e -Sc a le Ge no me Se q ue nc ing pro g ra m, inc lud ing Ce nte rs fo r Me nd e lia n Ge ne tic s 7

SLIDE 8

Millio n Ve te ra ns’ Pro g ra m (MVP)
Pa tie nt-Ce nte re d Outc o me s Re se a rc h Ne two rk (PCORne t)
Pha rma c o g e ne tic s Re se a rc h Ne two rk (PGRN)
Phe no type s a nd E

xpo sure s T

o lkit (Phe nX)
Po pula tio n Arc hite c ture using Ge no mic s a nd E

pid e mio lo g y (PAGE )

Pre c isio n Me d ic ine I

nitia tive (PMI)

U.S. Air F
rc e Pe rso nalize d a nd Pre c isio n Ca re

SLIDE 9

Objectives of major genomic medicine programs related to implementation of genomic medicine. Objectives Related to Genomic Medicine Implementation Focus Programs Related Programs UDN NSIGHT CSER eMERGE IGNITE ClinGen GM Mtgs G2MC AFMS CMG CPIC GA4GH GAPH IOM ISCC LSAC PAGE PhenX Improve genomic diagnostic methods X X X X Facilitate research in undiagnosed and/or Mendelian diseases X X X Expand scale of genomic data available in newborns X Advance understanding of disorders of newborns X Research ethical/legal/social issues in genome sequencing X X X Interpret sequence data in variety of clinical contexts X X Integrate genomic data into patient care X X X X X Incorporate actionable variants into EMR, develop CDS X X X X X Educate clinicians and patients on genomics in clinical care X X X X X X X X

Develop electronic phenotypes X

Identify variants related to complex traits X X X X X X Characterize pharmacogenetic variants and use in care X X X Assess outcomes of using genomic information in clinical care X X X X Assess penetrance of potentially actionable variants X Translate implementation outside highly specialized centers X X Define and share processes of implementation, sustainability X X X X X X X Share genotype/phenotype info through open databases X X Standardize clinical annotation and interpretation X

Improve understanding of variation in diverse populations X X X Assess actionability of genes and variants for clinical use X X Identify, address barriers to genomic medicine implementation X X X X Promote interaction and collaboration, reduce duplication X X X X X X X X Serve as clearinghouse, knowledge base for genomic medicine X X X Use genomics to enable new drug development X X Create genomics-enabled learning health care systems X X X Develop evidence base for clinical use of novel diagnostics X UDN NSIGHT CSER eMERGE IGNITE ClinGen GM Mtgs G2MC CMG CPIC GA4GH GAPH IOM ISCC LSAC PAGE PhenX

SLIDE 10

Barriers to genomic medicine implementation as identified by focus and related programs. Barriers Identified Focus Programs Related Programs UDN NSIGHT CSER eMERGE IGNITE ClinGen GM Mtgs G2MC CMG CPIC GAPH GTEx GS-IT IOM ISCC LSAC MVP PAGE PCORNet PhenX PGRN DATA/INFORMATION NEEDS Evidence base for implement’n incl long-term outcomes X X X X X Common data elements X X X Development, validation of phenotypes X X Specific drug response phenotypes to add to trials X Publicly available genotype/phenotype info X X X Framework for classifying/curating actionable variants X X Unclear penetrance of actionable genes X Impact of variants in ancestrally diverse populations X RAPIDLY EVOLVING NATURE OF GENOMIC INFO Evolving molecular testing panels X Changes in evidence and subsequent treatment X Division between discovery and implementation X CLINICAL IMPLEMENTATION ISSUES High cost of sequencing, data processing X X Targeted testing vs genome-scale sequencing X Limited use of standardized EMR terms, ontologies X X Concise, comprehensive, interoperable lab reports X X Integration of genomic data in learning healthcare system X Turnaround in clinically emergent settings X Use cases for genomic CDS development X Limited usefulness and interoperability of CDS X X X X Rapidly evolving EMRs X Limited transportability of clinical workflows, protocols X Differing education needs across professional levels X Returning incidental findings X UDN NSIGHT CSER eMERGE IGNITE ClinGen GM M G2MC CMG CPIC GAPH GTEX GS-IT IOM ISCC LSAC MVP PAGE PCORNe PhenX PGRN X 10

SLIDE 11

Barriers Identified Focus Programs Related Programs UDN NSIGHT CSER eMERGE IGNITE ClinGen GM Mtgs G2 G2MC CMG CPIC GAPH GTEX GS-IT IOM ISCC LSAC MVP PAGE PCORNet PhenX PGRN REGULATORY NEEDS Central IRB X Sharing identifiable data across collaborating sites X Privacy threats (FISMA compliance for UDN) X X Regulations impeding return of results X X Need for cloud computing X Reimbursement policies and regulations OTHER Lack of centralized iPS cell repository X Installing and using sequence analysis software X Different tools for variant calling give different results X Finding and interpreting CNVs and SVs X Difficulty focusing on specific genes in massive BAMs X Need secure systems enabling access by many users X Harnessing social media and crowdsourcing methods X Increasing visibility and use of tools; tracking uptake X Need for bedside back to bench research X Publication standards for rapid research results X Worldwide ascertainment of Mendelian families X UDN NSIGHT CSER eMERGE IGNITE ClinGen GM Mtgs G2 G2MC CMG CPIC GAPH GTEX GS-IT IOM ISCC LSAC MVP PAGE PCORNet PhenX PGRN X X X 11

SLIDE 12

IMPACT F UL PUBL ICAT IONS – GE NOMIC ME DICINE VIII ME E T ING E nhanc e d CARE for RARE Ge ne tic Dise ase s in Canada (K

im Bo yc o tt a nd Ale x Ma c K e nzie )

T he c linic al utility of whole - e xome se que nc ing in the c onte xt of r ar e dise ase s – the c hanging tide s of me dic al pr ac tic e .

Ng uye n MT ,Cha rle bo is K , 2014-11-25, Clinic al Ge ne tic s Who le -e xo me se q ue nc ing (WE S) c a rrie s the po te ntia l to fa c ilita te the id e ntific a tio n o f d ise a se c a using g e ne s. T his is pa rtic ula rly re le va nt c o nc e rning ra re d ise a se s, whic h pro ve s pa rtic ula rly d iffic ult fo r physic ia ns to d ia g no se . Ho we ve r, the c o mple xity o f this te c hno lo g y re nd e rs its a pplic a b ility o nto the c linic al se tting unc e rta in. Our stud y thus a ims to und e rsta nd physic ia ns' pe rspe c tive s re g a rd ing the c linic al utility o f WE S, pa rtic ula rly fo r pro vid ing a d ia g no sis fo r pa tie nts with ra re d ise a se s.

Mutations in PNPL A6 ar e linke d to photor e c e ptor de ge ne r ation and var ious for ms of c hildhood blindne ss.

K mo c h S,Ma je wski J,Ca o S, F a himiniya S, Re n H, Ma c Do nald I M, L

pe z I, Sun V,

K e ser V, Khan A, Stránecký V, Hartmannová H, Přistoupilová A, Hodaňová K,

Piherová L, Kuchař L, Baxová A, Chen R, Barsottini OG, Pyle A, Griffin H, Splitt M,

Sallum J, T

lmie JL

, Sa mpso n JR, Chinne ry P, Ba nin E , Sha ro n D, Dutta S, Gre b le r R, He lfric h-F

e rste r C, Pe d ro so JL

, K re tzsc hma r D, Ca yo ue tte M, K

e ne ko o p RK

, Ca re 4Ra re Ca na d a 2015-01-09, Na ture Co mmunic a tio ns

Autism Spe c tr um Disor de r s: Ge nome s to Outc ome s (Ste phe n Sc he re r a nd Pe te r

Sza tma ri)

Autism spe c tr um disor de r : advanc e s in e vide nc e - base d pr ac tic e

E vd o kia Ana g no sto u MD, L

nnie Zwa ig e nb a um MD, Pe te r Sza tma ri MD, E

ric F

mb o nne MD, Brid g e t A. F

e rna nd e z MD, Ma rc Wo o d b ury-Smith MD PhD, Je ssic a Bria n PhD, Susa n Bryso n PhD, I sa b e l M. Smith PhD, Ire ne Drmic PhD, Ja ne t

A. Buc ha na n PhD, We nd y Ro b e rts MD, Ste phe n W. Sc he re r PhD

Ca na d ia n Me d ic al Jo urna l, Ja nua ry 13 2014 I n this re vie w, we o utline the c urre nt und e rsta nd ing o f ASD a nd sug g e st b e st pra c tic e s fo r prima ry c a re a nd spe c ialize d c linic s b a se d o n e vid e nc e fro m ra nd o mize d c o ntro lle d tria ls (RCT s) o r syste ma tic re vie ws, if a va ila ble .

SLIDE 13

Br ain- e xpr e sse d e xons unde r pur ifying se le c tion ar e e nr ic he d for de novo mutations in autism spe c tr um disor de r

Mo hamme d Ud d in, K ristiina T a mmimie s, Gio va nna Pe lle c c hia, Ba b a k Alipa na hi, Ping zha o Hu, Zhuo zhi Wa ng , Da lila Pinto , L yne tte L a u, T ho ma s Nalpa tha mkala m, Christia n R Ma rshall, Be nja min J Ble nc o we , Bre nd a n J F re y, Da nie le Me ric o , Rya n K C Yue n & Ste phe n W Sc he re r Na ture Ge ne tic s 46, 742–747 (2014) A unive rsal c halle ng e in g e ne tic stud ie s o f a utism spe c trum diso rd e rs (ASDs) is d e te rmining whe the r a g ive n DNA se q ue nc e alte ra tio n will ma nife st a s d ise a se . Amo ng d iffe re nt po pula tio n c o ntro ls, we o b se rve d , fo r spe c ific e xo ns, a n inve rse c o rre la tio n b e twe e n e xo n e xpre ssio n le ve l in b ra in a nd b urd e n o f ra re misse nse muta tio ns. F

r g e ne s tha t ha rb o r d e no vo muta tio ns pre d ic te d to b e

d e le te rio us, we fo und tha t spe c ific c ritic a l e xo ns we re sig nific a ntly e nric he d in ind ivid uals with ASD re la tive to the ir sib ling s witho ut ASD. Our re sults sug g e st tha t b ra in-e xpre sse d e xo ns und e r purifying se le c tio n sho uld b e prio ritize d in g e no type -phe no typ e stud ie s fo r ASD a nd re la te d ne uro d e ve lo pme nta l c o nd itio ns.

PACE

‘Omic s: Pe r

sonalize d, Ac c e ssible , Cost- E ffe c tive Applic ations of ‘Omic s T e c hnologie s (Chisto phe r Mc Ca b e a nd T

a nia Bub e la )

Value - E ngine e r e d T r anslation: De ve loping Biothe r ape utic s T hat Align With He alth- Syste m Ne ed s

T a nia Bub e la , PhD, JD, a nd Christo phe r Mc Ca b e , PhD http :/ / www.a jmc .c o m/ jo urnals/ e vid e nc e -b a se d -d ia b e te s- ma na g e me nt/ 2014/ july-a ug ust-2014/ Va lue -E ng ine e re d -T ra nslatio n-De ve lo ping - Bio the ra pe utic s-T ha t-Alig n-With-He a lth-Syste m-Ne e d s# stha sh.66MQ1q 6U.d puf AJMC July 21, 2014 He re we d e sc rib e the Va lue -E ng ine e re d T ra nsla tio n (VET ) fra me wo rk tha t c o uple s d e ve lo pme nt d e c isio ns alo ng the tra nsla tio na l c o ntinuum with the pro d uc tio n o f a “re imb ursa ble e vid e nc e d o ssie r.” It a ssists te c hno lo g y d e ve lo p- e rs in c o mpre he nd ing the e vid e nc e re q uire me nts o f he a lthc a re pa ye rs, b o th public a nd priva te , in d iffe re nt ma rke ts. Co nc o mita ntly, it suppo rts pa ye rs in e va lua ting a b ro a d e r ra ng e o f fa c to rs fo r no ve l b io -the ra pe utic s tha t ma y a d d re ss unme t he a lthc a re ne e d s. F inally it b e ne fits the pub lic a nd pa tie nts, who re q uire b e tte r a nd mo re c o st-e ffe c tive the ra pe utic s a nd d ia g no stic s, b y info rming d e c isio ns o n he alth insura nc e c o ve ra g e a nd o ut-o f-po c ke t e xpe nse s.

Se e mo re a t: http :/ / www.a jmc .c o m/ jo urnals/ e vid e nc e -b a se d -d ia b e te s-

SLIDE 14

ma na g e me nt/ 2014/ july-a ug ust-2014/ Va lue -E ng ine e re d -T ra nslatio n-De ve lo ping - Bio the ra pe utic s-T ha t-Alig n-With-He a lth-Syste m- Ne e d s# stha sh.66MQ1q 6U.Ac kxl6o o .d puf

Innovative Che moge nomic T

ols to Impr
ve Outc ome in Ac ute Mye loid

L e uke mia (Guy Sa uva g e a u a nd Jo sé e Hé b e rt) Ide ntific ation of small mole c ule s that suppor t human le uke mia ste m c e ll ac tivity e x vivo

Ca ro line Pa b st, Ja na K ro sl, I ma n F a re s, Ge ne viè ve Bo uc he r, Ré je a n Rue l, Anne Ma rinie r, Sé b a stie n L e mie ux, Jo sé e Hé b e rt & Guy Sa uva g e a u Na ture Me tho d s 11, 436–442 (2014) L e uke mic ste m c e lls (L SCs) a re c o nsid e re d a ma jo r c a use o f re la pse in a c ute mye lo id le uke mia (AML ). De fining pa thwa ys tha t c o ntro l L SC se lf-re ne wal is c ruc ial fo r a b e tte r und e rsta nd ing o f und e rlying me c ha nisms a nd fo r the d e ve lo pme nt o f ta rg e te d the ra pie s. Ho we ve r, c urre ntly a va ilable c ulture c o nd itio ns d o no t pre ve nt sp o nta ne o us d iffe re ntia tio n o f L SCs, whic h g re a tly limits the fe a sib ility o f c e ll-b a se d a ssa ys. T

o ve rc o me the se c o nstra ints we

c o nd uc te d a hig h-thro ug hput c he mic al sc re e n a nd id e ntifie d small mo le c ule s tha t inhib it d iffe re ntia tio n a nd suppo rt L SC a c tivity in vitro . Simila r to re p o rts with c o rd blo o d ste m c e lls, se ve ra l o f the se c o mpo und s suppre sse d the a ryl- hyd ro c a rb o n re c e p to r (AhR) pa thwa y, whic h we sho w to b e ina c tive in vivo a nd ra pidly a c tiva te d e x vivo in AML c e lls. We a lso id e ntifie d a c o mpo und , UM729, tha t c o lla b o ra te s with AhR suppre sso rs in pre ve nting AML c e ll d iffe re ntia tio n. T

g e the r, the se find ing s pro vid e ne wly d e fine d c ulture c o nd itio ns

fo r impro ve d e x vivo c ulture o f prima ry huma n AML c e lls.

Vir al and Human Ge ne tic Pr e dic tor s of Re sponse to HIV T he r apie s (Ric ha rd

Ha rrig a n a nd Julio Mo nta ne r)

Ge ogr aphic and T e mpor al T r e nds in the Mole c ular E pide miology and Ge ne tic Me c hanisms of T r ansmitte d HIV- 1 Dr ug Re sistanc e : An Individual- Patie nt- and Se que nc e - L e ve l Me ta- Analysis.

S Me d . 2015 Apr 7; 12(4):e 1001810. d o i: 10.1371/ jo urna l.pme d .1001810.

e Co lle c tio n 2015. Rhe e SY, Bla nc o JL , Jo rd a n MR, T a ylo r J, L e me y P, Va rg he se V, Ha me rs RL , Be rta g no lio S, Rinke d e Wit T F , Ag ho ke ng AF , Alb e rt J, Avi R, Avila -Rio s S, Be sso ng PO, Bro o ks JI, Bo uc he r CA, Brumme ZL , Busc h MP, Bussma nn H, Cha ix ML , Chin

SLIDE 15

BS, D'Aq uin T T , De Ga sc un CF , De ra c he A, De sc a mps D, De shpa nd e AK , Djo ko CF , E shle ma n SH, F le ury H, F ra ng e P, F ujisa ki S, Ha rrig a n PR, Ha tto ri J, Ho lg uin A, Hunt GM, I c himura H, K a le e b u P, K a tze nste in D, K ie rtib ura na kul S, K im JH, K im SS, L i Y, L utsa r I, Mo rris L , Nd e mb i N, Ng K P, Pa ra nja pe RS, Pe e te rs M, Po lja k M, Pric e MA, Ra g o nne t-Cro nin ML , Re ye s-T e rá n G, Ro lla nd M, Sirivic ha ya kul S, Smith DM, So a re s MA, So ria no VV, Sse mwa ng a D, Sta no je vic M, Ste fa ni MA, Sug iura W, Sung ka nupa rph S, T a nuri A, T e e K K , T ruo ng HH, va n d e Vijve r DA, Vid a l N, Ya ng C, Ya ng R, Ye b ra G, I

a nnid is JP, Va nd a mme AM, Sha fe r RW.

Re g io na l a nd sub typ e -spe c ific muta tio na l pa tte rns o f HIV-1 tra nsmitte d d rug re sista nc e (T DR) a re e sse ntia l fo r info rming first-line a ntire tro viral (ARV) the ra p y g uid e line s a nd d e sig ning d ia g no stic a ssa ys fo r use in re g io ns whe re sta nd a rd g e no typ ic re sista nc e te sting is no t a ffo rd a ble . We so ug ht to und e rsta nd the mo le c ula r e pid e mio lo g y o f T DR a nd to id e ntify the HIV-1 d rug -re sista nc e muta tio ns re spo nsib le fo r T DR in d iffe re nt re g io ns a nd virus sub type s.

PE GASUS: Pe r sonalize d Ge nomic s for Pr e natal Ane uploidy Sc r e e ning Using Mate r nal Blood (F

ra nç o is Ro usse a u a nd Sylvia L a ng lo is)

Ide ntific ation of tr isomy 18, tr isomy 13, and Down syndr

me fr
m mate r

nal plasma.

Ge ka s J1, L a ng lo is S2, Ra vitsky V3, Aud ib e rt F 4, va n d e n Be rg DG5, Ha id a r H3, Ro usse a u F 6. Appl Clin Ge ne t. 2014 Jul 7;7:127-31. d o i: 10.2147/ T ACG.S35602. e Co lle c tio n 2014. Ab stra c t Curre nt pre na ta l d iag no sis fo r fe ta l a ne uplo id ie s (inc lud ing triso my 21 [T 21]) g e ne ra lly re lie s o n an initia l b io c he mic al se rum-b a se d no ninva sive pre na ta l te sting (NIPT ) a fte r whic h wo me n who a re d e e me d to b e a t hig h risk a re o ffe re d a n inva sive c o nfirma to ry te st (a mnio c e nte sis o r c ho rio nic villi sa mpling fo r a fe ta l ka ryo type ), whic h is a sso c ia te d with a risk o f fe ta l misc a rria g e . Re c e ntly, g e no mic s-b a se d NIPT (g NIPT ) wa s pro po se d fo r the a na lysis o f fe ta l g e no mic DNA c irc ula ting in ma te rna l blo o d . T he d iffusio n o f this te c hno lo g y in ro utine pre na ta l c a re c o uld b e a ma jo r b re a kthro ug h in pre na ta l d iag no sis, sinc e initia l re se a rc h stud ie s sug g e st tha t this no ve l a ppro a c h c o uld b e ve ry e ffe c tive a nd c o uld re d uc e sub sta ntia lly the numb e r o f inva sive pro c e d ure s. Ho we ve r, the limita tio ns o f g NIPT ma y b e und e ra ppre c ia te d . In this re vie w, we e xamine c urre ntly publishe d lite ra ture o n g NIPT to hig hlig ht a d va nta g e s a nd limita tio ns. At this time , the pe rfo rma nc e o f g NIPT is re la tive ly we ll-d o c ume nte d o nly in hig h-risk pre g na nc ie s fo r T 21 a nd triso my 18. T his a d d itio na l sc re e ning te st ma y b e a n

SLIDE 16

p tio n fo r wo me n c la ssifie d a s hig h-risk o f a ne uplo id y who wish to a vo id inva sive

d ia g no stic te sts, b ut it is c ruc ial tha t p ro vid e rs c a re fully c o unse l pa tie nts a b o ut the te st's a d va nta g e s a nd limita tio ns. T he g NIPT is c urre ntly no t re c o mme nd e d a s a first-tie r pre na ta l sc re e ning te st fo r T

21. Sinc e g NIPT

is no t c o nsid e re d a s a d ia g no stic te st, a po sitive g NIPT re sult sho uld alwa ys b e c o nfirme d b y a n inva sive te st, suc h a s a mnio c e nte sis o r c ho rio nic villus sampling . Va lid a tio n stud ie s a re ne e d e d to o p timally intro d uc e this te c hno lo g y into the e xisting ro utine wo rkflo w o f pre na ta l c a re .

SLIDE 17

F OCUS PROGRAMS

SLIDE 18

Ge no mic Me dic ine VIII – Summar y o f F

c us Pr
gr

am CL INGE N

am Name and We b site : Clinic a l Ge no me Re so urc e , www.c linic a lg e no me .o rg PIs and F unde d Site s:

U41 HG006834-01 He idi L . Re hm, Ph.D., Brig ha m a nd Wo me n's Ho spita l, Bo sto n, MA Christa L . Ma rtin, Ph.D. Da vid H. L e db e tte r, Ph.D. Ge ising e r He a lth Syste m, Da nville , PA Ge ising e r He a lth Syste m, Da nville , PA Ro b e rt L . Nussb a um, M.D. Unive rsity o f Ca lifo rnia , Sa n F ra nc isc o , C A U01 HG007437-01 Jo na tha n S. Be rg , M.D., Ph.D Ja me s P. E va ns, M.D., Ph.D Mic ha e l S. Wa tso n, Ph.D. Da vid H. L e db e tte r, Ph.D. Unive rsity o f No rth Ca ro lina , Cha pe l Hill, NC Unive rsity o f No rth Ca ro lina , Cha pe l Hill, NC ACMG, Be the sda , MD Ge ising e r He a lth Syste m, Da nville , PA U01 HG007436-01 Ca rlo s D. Busta ma nte , Ph.D. Sta nfo rd Unive rsity, Pa lo Alto , C A Sha ro n E. Plo n, M.D., Ph.D., Ba ylo r Co lle g e o f Me dic ine , Ho usto n, T X ClinVa r Me lissa L a ndrum, Ph.D. Ste ve She rry, Ph.D. NCBI I ntra mura l Pro g ra m, Be the sda , MD Missio n: Building a g e no mic kno wle dg e b a se to impro ve pa tie nt c a re Ob je c tive s: 1. Sha re g e no mic a nd phe no typic da ta thro ug h a c e ntra l da ta b a se fo r c linic a l a nd re se a rc h use 2. De fine the re vie w le ve l fo r ClinVa r sub missio ns a nd re vie w e xpe rt pa ne l a pplic a tio ns 3. Sta nda rdize the c linic a l a nno ta tio n a nd inte rpre ta tio n o f g e no mic va ria nts 4. I mpro ve o ur unde rsta nding o f va ria tio n in dive rse po pula tio ns to impro ve inte rpre ta tio n o f g e ne tic te sting o n a g lo b a l sc a le 5. De ve lo p ma c hine -le a rning a lg o rithms to impro ve the thro ug hput o f va ria nt inte rpre ta tio n 6. I mple me nt e vide nc e -b a se d e xpe rt c o nse nsus fo r c ura ting g e ne s a nd va ria nts 7. Asse ss the a c tio n a b ility o f g e ne s a nd va ria nts to suppo rt the ir use in c linic a l c a re syste ms 8. Disse mina te the kno wle dg e a nd re so urc e s fo r unre stric te d use in the c o mmunity F unding Pe rio d and F Y14 T

tal:

* Co -funding fro m NCI & NI CHD Curre nt I ntra-Pro g ram Wo rking Gro ups: 1.

IT Sta nda rds & Da ta Submission: F

a c ilita te sub missio n o f da ta to ClinVa r. 2.

Struc tura l Va ria tion: De ve lo p a do sa g e ma p o f the huma n g e no me thro ug h g e ne c ura tio n, c o lle c t c o py numb e r

da ta fro m c linic a l la b o ra to rie s a nd pub lic g e no mic s e ffo rts, a nd b uild to o ls to suppo rt sta nda rdiza tio n o f c o p y numb e r inte rpre ta tio n. 3.

Se que nc e Va ria tion: Re c ruit the sub missio n o f c ura te d se q ue nc e va ria nts to ClinVa r a nd le a d a c tivitie s to

impro ve the q ua lity a nd utility o f sha re d da ta . 4.

Phe notype : Suppo rt the c o lle c tio n a nd sub missio n o f phe no typic da ta to ClinGe n re so urc e s.

E duc a tion, E ng a g e me nt, a nd Ac c e ss: F

ste r c o mmunity e ng a g e me nt in a ll a spe c ts o f the ClinGe n pro je c t

thro ug h e duc a tio n, o utre a c h, a nd re so urc e de ve lo pme nt. 6.

Conse nt a nd Disc losure Re c omme nda tions (CADRe ): E

xplo re the E L SI issue s re la ting to re po rting a c tio na b ility o f pa rtic ula r va ria nts. 7.

Ge ne Cura tion: De ve lo p e vide nc e -b a se d me tho ds fo r e va lua ting g e ne -dise a se a sso c ia tio ns to info rm the

c o mmunity o n the stre ng th o f the se a sso c ia tio ns fo r g e ne s o ffe re d fo r te sting . 8.

Ac tiona bility: I

de ntify tho se huma n g e ne s tha t, whe n sig nific a ntly a lte re d, c o nfe r a hig h risk o f se rio us dise a se tha t c o uld b e pre ve nte d o r mitig a te d if the risk we re kno wn. 9.

Clinic a l Doma ins: Cre a te a c o mpre he nsive , sta nda rdize d kno wle dg e b a se o f g e ne s a nd va ria nts re le va nt to the

do ma ins o f Cardio vasc ular Dise ase , He re ditary Canc e r, So matic Canc e r, I nb o rn E rro rs o f Me tab o lism, and Pharmac o g e no mic s.

F Y13 F Y14 F Y15 F Y16 T

ta l*

$5.8M $7.5M $7.5M $7.2M $28.0M

SLIDE 19

10.

Informa tic s: Co o rdina te the a c q uisitio n, a na lysis, a nd disse mina tio n o f ClinGe n re so urc e da ta .

11.

Da ta Mode l: Pro vide a c o mmo n se t o f de finitio ns a nd c o nsiste nt re pre se nta tio n o f c o re c o nc e pts, a ttrib ute s, a nd

te rmino lo g y to suppo rt ClinGe n & ha rmo nize with re le va nt e ffo rts. 12.

E le c tronic He a lth Re c ord (E HR): Aims to e nsure tha t the ClinGe n re so urc e is de sig ne d to b e a c c e ssib le to

pro vide rs a nd pa tie nts thro ug h e le c tro nic he a lth re c o rd a nd re la te d syste ms. Majo r Co llab o ratio ns and T he ir Go als:

CSER: F

a c ilita ting ClinVa r sub missio ns, pilo ting pa tho g e nic ity c a lc ula to r, c ro ss-re pre se nta tio n o n ClinGe n’ s So ma tic Ca nc e r WG

Cro ss-re pre se nta tio n o n ma ny re la te d (inc luding the Glo b a l Allia nc e fo r Ge no mic s a nd He a lth, DE

CI PHE R, Ma tc hma ke r I nitia tive , I OM, ACMG, CPI C, F re e -the -Da ta ) to e nha nc e c o mmunic a tio n a nd c o lla b o ra tio n. Re so urc e s and T

o ls Pro duc e d:

1. Ge no me Co nne c t: ClinGe n’ s pa tie nt po rta l (a va ila b le o nline ) 2. Clinic a l va lidity fra me wo rk (a va ila b le o nline ) 3. Ac tio na b ility sc o ring pro c e ss a nd e vide nc e summa rie s (a va ila b le o nline ) 4. E HR we b re so urc e s (a va ila b le o nline ) Ke y Pub lic atio ns: 1. Re hm HL , Be rg JS, Bro o ks L D, Busta ma nte CD, E va ns JP, L a ndrum MK, L e d b e tte r DH, Ma g lo tt DR, Ma rtin CL , Nussb a um RL , Plo n SE, Ra mo s E M, She rry ST , Wa tso n MS, o n b e ha lf o f ClinGe n. ClinGe n: T he Clinic a l Ge no me Re so urc e . I n Pre ss. 2. Ra mo s E M, Din-L

vine sc u C, Be rg JS, e t al., Willia ms MS., Cha ra c te rizing Ge ne tic Va ria nts fo r Clinic a l Ac tio n.

Ame ric an Jo urnal o f Me dic al Ge ne tic s Part C: Se minars in Me dic al Ge ne tic s (spe c ia l issue o n imple me nta tio n o f g e no mic me dic ine ), 166, No . 1, pp . 93-104. 2014. Majo r Ob stac le s o r Ne e ds E nc o unte re d:

Ma jor Ne e ds Approa c he s Imple me nte d/ Propose d to O ve rc ome Obsta c le s

Co nse nsus fra me wo rks & ro b ust c ura tio n e nviro nme nt fo r a sse ssing c linic a l sig nific a nc e o f g e ne s & va ria nts Cre a te d a c linic a l va lidity ma trix a nd de ta ile d sc o ring pro c e ss; Cre a te d se mi-q ua ntita tive a c tio na b ility me tric ; I nfo rma tic s te a m is de ve lo ping v1

f a n o nline c ura tio n inte rfa c e

Ric h g e no typic & phe no typic info rma tio n in pub lic re po sito rie s to info rm c ura tio n E xplo ring de ve lo pme nt o f a c o ntro lle d-a c c e ss re p o sito ry fo r c a se -le ve l da ta Co nsiste nt use o f o nto lo g ie s a nd dise a se te rms Se le c ting o nto lo g ie s a nd te rm lists to use a c ro ss ClinGe n syste ms a nd ClinVa r sub missio ns NHGRI Pro g ram Offic ials: E rin Ra mo s, L isa Bro o ks, Ca ro lyn Hutte r, K e n Wile y

SLIDE 20

Ge no mic Me dic ine VIII – Summar y o f F

c us Pr
gr

am CSE R

Pro g ram Name and We b site : Clinic a l Se q ue nc ing E xplo ra to ry Re se a rc h (CSE R) Co nso rtium, We b site : https:/ / c se r-c o nso rtium.o rg / PI s and Funde d Site s (U-Grants and Co o rdinating Ce nte r) Sha ro n Plo n, Will Pa rso ns Ba ylo r Co lle g e o f Me dic ine (BCM) Ro b e rt Gre e n Brig ha m a nd Wo me n’ s Ho spita l I a n K ra ntz, Na nc y Spinne r Childre n’ s Ho spita l o f Phila de lphia (CHOP) L e vi Ga rra wa y, Pa si Ja nne Da na F a rb e r Ca nc e r I nstitute (DF CI )/ Bro a d I nstitute Gre g Co o pe r, Ric k Mye rs Hudso nAlpha K a trina Go dda rd , Be n Wilfo nd K a ise r Pe rma ne nte Arul Chinna iya n Unive rsity o f Mic hig a n Ja me s E va ns, a nd o the rs Unive rsity o f No rth Ca ro lina , Cha pe l Hill Ga il Ja rvik Unive rsity o f Wa shing to n Ga il Ja rvik, a nd o the rs Unive rsity o f Wa shing to n (Co o rdina ting Ce nte r) R-Gra nts: 9 g ra nts fo c use d o n re turn o f re sults, funde d b y the Divisio n o f Ge no mic s & So c ie ty NHGRI I ntra mura l: L e s Bie se c ke r, ClinSe q study Ob je c tive s: 1. Ge ne ra te a nd inte rpre t g e no mic se q ue nc e da ta o n pa tie nts in a va rie ty o f c linic a l c o nte xts; 2. De ve lo p me tho ds fo r inte g ra ting c o mpre he nsive g e no mic se q ue nc e da ta into pa tie nt c a re , inc luding : a ) g e ne ra ting a nd a pplying g e no mic se q ue nc e da ta within the c linic a l wo rkflo w; b ) inte rpre ting a nd tra nsla ting se q ue nc e da ta fo r re fe rring c linic ia ns; a nd c ) c o mmunic a ting se q ue nc ing re sults to the pa tie nt, pro vide r a nd fa mily. 3. E xa mine the e thic a l, le g a l, a nd psyc ho so c ia l implic a tio ns o f b ring ing se q ue nc e da ta to the c linic . I de ntify the b e ne fits a nd ha rms o f g e no mic se q ue nc ing whe n a pplie d in dive rse c linic a l c o nte xts. F unding Pe rio d and F Y14 T

tal: (U g rants o nly)

F Y2011-F

Y2017. $15.4M HG ($2.9M NCI

) in F Y14 Curre nt I ntra-Pro g ram Wo rking Gro ups: 1. Ac tio na b ility-Re turn o f Re sults 2. E le c tro nic He a lth Re c o rds (E HR) 3. Ge ne tic Co unse lo rs 4. I nfo rme d Co nse nt a nd Go ve rna nc e 5. Outc o me s a nd Me a sure s 6. Pe dia tric s 7. Phe no typing Me a sure s a nd Ana lysis 8. Se q ue nc ing Sta nda rds 9. T umo r Se q ue nc ing Majo r Co llab o ratio ns and T he ir Go als:

e ME

RGE : sha re e xpe rie nc e a nd le sso ns le a rne d , ide ntify prio ritie s fo r (re turn o f re sults, E HR)

ClinGe n: c o o rdina te va ria nt sub missio n; pro vide sc ie ntific e xpe rtise (tumo r, g e ne / va ria nt WGs)
Ge no me Se q ue nc ing Pro g ra m (L

SAC/ CMG/ GS-I T ): jo int me e ting s in 2012-2013 Re so urc e s and T

o ls Pro duc e d (re pre se ntative sample ):

1. ClinVa r de po sitio n (N = 2171 c o mple te d o r pe nding sub missio ns) 2. T ARGET da ta b a se o f c a nc e r g e ne s; PHIAL a na lysis pla tfo rm (DFCI ; PMI D 24836576) 3. So ftwa re / pla tfo rm fo r c linic a l e xo me s (BCM; PMI D 24088041) 4. Pro b a nd pe dig re e a pp (http:/ / pro b a nda pp.c o m/ ) (CHOP) 5. Disse mina tio n o f e xpe rtise , pro to c o ls a nd le sso ns le a rne d via hig h visib ility sc ie ntific c o nfe re nc e s (ACMG, ASHG, NSGC, ASCO, AACR, ASBH) a nd e xpe rt c o nsulta tio ns F ive Ke y Pub lic atio ns (3 CSER-wide , 2 sing le -site , fro m >140 p ub lic atio ns): 1. Ame ndo la L M, e t a l. Ac tio na b le e xo mic inc ide nta l finding s in 6503 pa rtic ipa nts: c ha lle ng e s o f va ria nt c la ssific a tio n. Ge no me Re s. 2015. PMI D 25741865

SLIDE 21

2. Ga lle g o CJ, e t a l. Ne xt-Ge ne ra tio n Se q ue nc ing Pa ne ls fo r the Dia g no sis o f Co lo re c ta l Ca nc e r a nd Po lyp o sis Syndro me s: A Co st-E ffe c tive ne ss Ana lysis. J Clin Onc o l. 2015. PMI D: 25940718 3. Gra y SW, e t a l. So c ia l a nd b e ha vio ra l re se a rc h in g e no mic se q ue nc ing : a ppro a c he s fro m the CSER Co nso rtium Outc o me s a nd Me a sure s Wo rking Gro up . Ge ne t Me d. 2014. PMI D: 24625446 4. Mc L a ug hlin HM, e t a l. A syste ma tic a ppro a c h to the re po rting o f me dic a lly re le va nt finding s fro m who le g e no me se q ue nc ing . BMC Me d Ge ne t. 2014. PMI D: 25714468 5. Shirts, e t a l. CSER a nd e ME RGE: Curre nt a nd Po te ntia l Sta te o f the Displa y o f Ge ne tic I nfo rma tio n in the E le c tro nic He a lth Re c o rd . I n pre ss, JAMI A.

Majo r Obstac le s o r Ne e ds E nc o unte r e d: Ma jor Obsta c le s or Ne e ds Approa c he s Imple me nte d or Propose d to Ove rc ome Obsta c le s

De fine the c linic a l c ha ra c te ristic s tha t sig na l whe n g e no me -sc a le se q ue nc ing vs. ta rg e te d te sting a ppro a c he s a re e ffe c tive in pa tie nt c a re . Utilize the re sults a c ro ss the dive rse c linic a l se tting s in CSE R to de te rmine mo st a ppro pria te te st pla tfo rm. Ad dre ss the c a sc a de o f info rma tio n flo wing fro m se q ue nc e d pa tie nts to pa tie nts a nd fa milie s, la b s, a nd c linic ia ns, with c o nside ra tio n o f do wnstre a m c ha lle ng e s (e .g ., priva c y). I nc o rpo ra te into a le a rning he a lthc a re syste m a nd c o o rdina te do wnstre a m e ffe c ts o f c a re de live ry. Co o rdina tio n with o the r g e no mic me dic ine a nd le a rning he a lthc a re e ffo rts. Cha ra c te rize the c o mple xity le a rne d fro m dive rse c linic a l se tting s a nd ide ntify b e st pra c tic e s fo r imple me nta tio n o f c linic a l g e no mic s. De ve lo p a fra me wo rk fo r c la ssifying a nd sig ning o ut va ria nts. Addre ss ma nua l a nd a uto ma te d c ura tio n re so urc e ne e d s; insuffic ie nt kno wle dg e ; c ha ng ing kno wle dg e re q uiring upda ting a nd re a na lysis. De ve lo pme nt o f re so urc e s to stre a mline c ura tio n fo r tumo r a nd g e rmline . E mpiric a lly a sse ss va ria b ility in inte rpre ta tio n (va ria nt “b a ke -o ff”) a nd va lue o f re a na lysis. I nc re a se the e vide nc e b a se fo r g e no mic te sting b y e va lua ting the lo ng -te rm c linic a l, psyc ho so c ia l a nd e c o no mic o utc o me s o f prima ry a nd se c o nda ry finding s. Do so a c ro ss e thnic , so c io e c o no mic , a nd c linic a l c o nte xts. L

ng itudina l fo llo w-up with a c c e ss to c o mpre he nsive
utc o me da ta . De dic a te d re c ruitme nt a nd study o f

dive rse pa tie nt po pula tio ns. I de ntific a tio n o f c o mmo n a nd ro b ust me tric s. De ve lo p c o nc ise ye t c o mpre he nsive la b o ra to ry re po rts fo r g e no mic re sults a nd inte g ra te into E HR's to suppo rt hig h q ua lity c linic a l c a re . De ve lo pme nt a nd disse mina tio n o f suc h re po rts ta ilo re d to dive rse c linic a l se tting s. Optimize info rme d c o nse nt, a na lysis a nd inte rpre ta tio n g ive n inhe re nt c linic a l time c o nstra ints, e spe c ia lly in se tting o f dise a se s with po o r pro g no sis a nd sho rt windo ws fo r a c tio n. Asse ss a nd re p o rt o n c o mmo n the me s a c ro ss the CSER site s while c o mme nting o n the uniq ue c ha lle ng e s o f diffe re nt c linic a l c o nte xts.

NHG RI Pr

am Offic ials: L

uc ia Hindo rff, Ca ro lyn Hutte r (DGM); Je a n Mc E we n, Da ve K a ufma n (DG&S). Cha rlisse Ca g a -Ana n, She ri Sc hully (NCI ).

SLIDE 22

Ge no mic Me dic ine VIII – Summar y o f F

c us Pr
gr

am e ME RGE

am Name and We b site : E

le c tro nic Me dic a l Re c o rds a nd Ge no mic s (e ME RGE ) Ne two rk, https:/ / e me rg e .mc .va nde rb ilt.e du/

PIs and F unde d Site s:

Ha ko n Ha ko na rso n Childre n’ s Ho spita l o f Phila de lphia Jo hn Ha rle y, I sa a c K

ha ne

Cinc inna ti Childre n’ s Ho spita l Me dic a l Ce nte r a nd Bo sto n Childre n’ s Ho spita l Ca the rine Mc Ca rty, Murra y Brillia nt E sse ntia I nstitute o f Rura l He a lth with Ma rshfie ld Clinic Da vid Ca re y, Ma rc Willia ms Ge ising e r He a lth Syste m E ric L a rso n, Ga il Ja rvik Gro up He a lth Co o pe ra tive with Unive rsity o f Wa shing to n I ftikha r K ullo , Christo phe r Chute Ma yo Clinic E rwin Bo tting e r I c a hn Sc ho o l o f Me dic ine a t Mo unt Sina i Re x Chisho lm, Ma ure e n Smith No rthwe ste rn Unive rsity Da n Ro de n Va nde rb ilt Unive rsity (Clinic a l Site ) Pa ul Ha rris Va nde rb ilt Unive rsity (Co o rdina ting Ce nte r)

Obje c tive s:

1. I nc o rpo ra te a c tio na b le g e ne tic risk fa c to rs into e le c tro nic me dic a l re c o rds (E MRs) fo r c linic a l re se a rc h, c linic a l de c isio n suppo rt, a nd c linic a l c a re 2. De ve lo p , imple me nt, a nd e va lua te the pro c e ss o f c linic ia n-pa tie nt e duc a tio n a nd c o mmunity c o nsulta tio n fo r re turn o f a c tio na b le g e ne tic va ria nts to E MRs 3. De ve lo p a nd va lida te e le c tro nic phe no typing a lg o rithms a nd de fine hig h-fide lity a lg o rithms c a pa b le o f c la ssifying phe no type s o f inte re st fo r g e no mic re se a rc h using E MRs a nd b io re po sito ry sa mple s 4. I de ntify g e ne tic va ria nts re la te d to c o mple x tra its thro ug h a sso c ia tio n a na lyse s 5. Cha ra c te rize pha rma c o g e ne tic (PGx) va ria tio n a nd its phe no typic ma nife sta tio ns a nd use PGx va ria nts to impro ve c linic a l c a re

F unding Pe r iod and FY14 T

tal:

F Y2008-F Y2014, re ne wa l pe nding , $11.2M in F Y14

Cur r e nt Intr a-Pr

am Wo r king Gr

ups:

1. Co nse nt, E duc a tio n, Re g ula tio n, a nd Co nsulta tio n (CE RC) 2. E le c tro nic He a lth Re c o rds (E HR) I nte g ra tio n 3. Ge no mic s 4. Phe no typing 5. Pe dia tric s 6. Re turn o f Re sults 7. e ME RGE-PGx Pha rma c o g e no mic s I nitia tive

Major Collabo r ations and T he ir Goals:

US Air Fo rc e Me dic a l Se rvic e Pe rso na lize d Me dic ine Pro g ra m: a do pt e ME

RGE g e no mic me dic ine imple me nta tio n me tho ds in milita ry me dic a l syste m

NCODE : e xplo re phe no typic ma nife sta tio ns o f func tio na l va ria nts

CSER: sha re me tho ds fo r Ro R, E

HR inte g ra tio n

Bio b a nk: sha re me tho ds fo r o utc o me a sc e rta inme nt thro ug h E HRs

Re so ur c e s and T

o ls Pr
duc e d:

1. Mo de l c o nse nt la ng ua g e 2. MyRe sults.o rg : Pa tie nt info rma tio n a b o ut g e ne tic re sults 3. Phe K B: Va lida te d e -phe no typing a lg o rithms

SLIDE 23

4. e ME RGE Re c o rd Co unte r 5. e le MAP: ha rmo nize phe no type da ta 6. c T AK E S: na tura l la ng ua g e pro c e ssing syste m fo r info rma tio n e xtra c tio n fro m E MRs 7. SPHI NX : A da ta e xplo ring to o l fo r g e ne tic s re la te d drug re spo nse hypo the sis g e ne ra tio n 8. Phe WAS Ca ta lo g : A c a ta lo g c o nta ins the Phe WAS re sults fo r 3,144 sing le -nuc le o tide po lymo rphisms (SNPs) pre se nt in the NHGRI GWAS Ca ta lo g 9. Ge no mic Clinic a l De c isio n Suppo rt Artifa c t Re po sito ry (in de ve lo pme nt, g o live June 2015)

F ive Ke y Public atio ns:

1. Go tte sma n O, e t a l. T he E le c tro nic Me dic a l Re c o rds a nd Ge no mic s (e ME RGE ) Ne two rk: Pa st, Pre se nt a nd F uture . Ge ne t Me d 2013 Oc t;15(10):761-71. 2. Ja rvik GP, e t a l. Re turn o f Ge no mic Re sults to Re se a rc h Pa rtic ipa nts: T he flo o r, the c e iling , a nd c ho ic e s in-b e twe e n. Am J Hum Ge ne t 2014 94:818–826. T his pa pe r wa s c ho se n a s o ne o f the to p 10 pa pe rs in 2014 b y AJHG. 3. De nny JC, e t a l. Syste ma tic c o mpa riso n o f phe no me -wide a sso c ia tio n study o f E MR da ta a nd g e no me -wide a sso c ia tio n study da ta . Na t Bio te c hno l 2013. 4. De nny JC, e t a l. Va ria nts ne a r F OXE 1 a re a sso c ia te d with hypo thyro idism a nd o the r thyro id c o nditio ns. Am J Hum Ge ne t 2011. 5. L

ukide s G e t a l., Ano nymiza tio n o f E

MRs fo r va lida ting g e no me -wide a sso c ia tio n studie s. PNAS 2010.

Majo r Obstac le s o r Ne e ds E nc o unte r e d: Ma jor Obsta c le s or Ne e ds Approa c he s Imple me nte d or Propose d to Ove rc ome Obsta c le s

I nc re a sing a do ptio n o f sta nda rdize d E MR te rms E nha nc e c o lla b o ra tio ns with E MR ve ndo rs to pro mo te inte ro pe ra b ility Asse ssing o utc o me s o f g e no mic me dic ine imple me nta tio n De fine pro c e ss a nd he a lth/ c linic a l c a re

utc o me s, de ve lo p a nd disse mina te

a sse ssme nt to o ls Asse ssing pe ne tra nc e o f va ria nts in a c tio na b le g e ne s Assa y va ria nts in we ll-phe no type d pa rtic ipa nts with a de q ua te fa mily histo ry a nd o utc o me da ta Pro viding inte ro pe ra b le g e no mic CDS Sta nda rdize CDS to o ls a nd c re a te CDS lib ra ry Re d uc ing priva c y thre a ts De fine te c hnic a l a nd po lic y pro te c tio ns pro po rtio na l to thre a ts po se d b y da ta sha ring NHGRI Pro g ram Offic ials: Ro ng ling L i, K e nne th Wile y

SLIDE 24

Ge no mic Me dic ine VIII – Summar y o f F

c us Pr
gr

am G2MC

am Name and We b site : Glo b a l Ge no mic Me dic ine Co lla b o ra tive (G2MC), www.io m.e d u/ G2MC Ste e r ing Co mmitte e Me mbe r s:

Ma rc Ab ra mo wic z Unive rsité L ib re de Bruxe lle s, Be lg ium F a hd Al-Mulla K uwa it Unive rsity, Kuwa it Ste ve n Ble yl I nte rmo unta in He a lthc a re Wa sun Cha ntra tita Ra ma thib o di Ho spita l, Ba ng ko k, T ha ila nd Va jira Dissa nya ke Unive rsity o f Co lo mb o , Co lo mb o , Sri L a nka Ge o ffre y Ginsb urg Duke Unive rsity Anne K

lb e

Na tio na l He a lth Co mmitte e , Auc kla nd, Ne w Ze a la nd Bruc e Ko rf Unive rsity o f Ala b a ma Mic hia ki K ub o RI K E N, Yo ko ha ma , Ja pa n E rkki L e e g o Unive rsity o f T a rtu, T a rtu, E sto nia Ge rt Ma tthijs Unive rsity o f L e uve n, L e uve n, Be lg ium Ya a ko v Na pa rste k Ha da ssa h He b re w Unive rsity Ho spita l, Je rusa le m, I sra e l I re ne No rste dt I nno va tive Me dic ine s I nitia tive , Brusse ls, Be lg ium Ge o rg e Pa trino s Unive rsity o f Pa tra s, Pa tra s, Gre e c e Ga d Re nne rt Cla lit Na tio na l Pe rso na lize d Me dic ine Pro g ra m, Ha ifa , I sra e l Ro b yn Wa rd Unive rsity o f Que e nsla nd , St. L uc ia , Austra lia Jo hn Wo ng E u L i Na tio na l Unive rsity o f Sing a po re , Sing a po re

Obje c tive s: T

impro ve g lo b a l he a lth b y c a ta lyzing the imple me nta tio n o f g e no mic to o ls a nd

kno wle dg e into he a lth c a re de live ry g lo b a lly. Sp e c ific a lly, it is inte nde d to : 1. Se rve a s ne xus, c le a ring ho use , a nd kno wle dg e b a se fo r g e no mic me dic ine a c tivitie s g lo b a lly; 2. De ve lo p o pp o rtunitie s fo r g lo b a l g e no mic me dic ine de mo nstra tio n pro je c ts (imple me nta tio n a nd

utc o me s re se a rc h) a nd ;

3. Ca pture a nd disse mina te b e st pra c tic e s fo r g e no mic me dic ine (in b io info rma tic s, e duc a tio n, e vide nc e , pha rma c o g e no mic s, po lic y) a c ro ss the g lo b a l g e no mic me dic ine c o mmunity.

F unding Pe r iod and FY14 T

tal: No t a pplic a b le

Cur r e nt Intr a-Pr

am Wo r king Gr

ups:

1. Co mmunic a tio ns 2. Clinic ia n E duc a tio n 3. E vide nc e Ge ne ra tio n 4. I nfo rma tio n T e c hno lo g y/ b io info rma tic s 5. Pha rma c o g e no mic s 6. Po lic y

Majo r Collabo r ations and T he ir Goals:

Glo b a l Allia nc e fo r Ge no mic s a nd He a lth (G A4GH), to pro mo te c linic a l imple me nta tio n o f re le va nt
utputs o f G A4GH

Re so ur c e s and T

o ls Pr
duc e d:

1. Wo rksho p o n Re se a rc h Dire c tio ns in Ge ne tic a lly Me dia te d Ste ve ns Jo hnso n Syndro me / T

E pide rma l Ne c ro lysis, Ma rc h 2015, https:/ / www.g e no me .g o v/ 27560487

F ive Ke y Public atio ns:

1. Ma no lio T A e t a l., Glo b a l imple me nta tio n o f g e no mic me dic ine : We a re no t a lo ne . Sc ie nc e T ra nsla tio na l Me dic ine , in pre ss.

SLIDE 25

Majo r Obstac le s o r Ne e ds E nc o unte r e d: Ma jor Obsta c le s or Ne e ds Approa c he s Imple me nte d or Propose d to Ove rc ome Obsta c le s

L a c k o f e vide nc e o f imp a c t o f g e no mic me dic ine imple me nta tio n Pro mo te re se a rc h to fill e vide nc e g a ps Hig h c o st o f g e no mic te sting Co ntinue re se a rc h a nd de ve lo pme nt to drive c o sts do wnwa rd Ne e d fo r c linic ia n e duc a tio n a nd g e no mic c linic a l de c isio n suppo rt (CDS) Pro mo te c linic ia n e duc a tio n a t va rie ty o f le ve ls, ta ilo re d to multiple la ng ua g e s a nd c ulture s L a c k o f inte ro pe ra b ility o f c linic a l c a re syste ms within a nd a mo ng c o untrie s Asse ss mo de l pro g ra ms in nimb le se tting s whe re imple me nta tio n ha s wo rke d, a da pt a s fe a sib le

NHG RI and IOM Staff: T

e ri Ma no lio , Ada m Be rg e r, Me re dith Ha c kma nn

SLIDE 26

Ge no mic Me dic ine VIII – Summar y o f F

c us Pr
gr

am GM MT GS

Pro g ram Name and We b site : NHGRI Ge no mic Me dic ine Me e ting s a nd Wo rking Gro up (GMWG), http:/ / www.g e no me .g o v/ 27549225 GMWG Me mb e rs: Ca ro l Bult Ja c kso n L a b o ra to ry Re x Chisho lm No rthwe ste rn Unive rsity Ge o ff Ginsb urg Duke Unive rsity Ho wa rd Ja c o b Hudso nAlpha I nstitute fo r Bio te c hno lo g y Ma ry Re lling

St. Jude Childre n’ s Re se a rc h Ho spita l

Da n Ro de n Va nde rb ilt Unive rsity Ma rc Willia ms Ge ising e r He a lth Syste m

Obje c tive s: Assist in a dvising NHGRI

n re se a rc h ne e de d to e va lua te a nd imple me nt g e no mic me dic ine

1. Re vie w c urre nt pro g re ss, ide ntify re se a rc h g a ps a nd a ppro a c he s fo r filling the m 2. I de ntify a nd pub lic ize ke y a dva nc e s 3. Pla n g e no mic me dic ine me e ting s fo c using o n time ly the me s 4. F a c ilita te c o lla b o ra tio ns, c o o rdina tio n 5. E xplo re mo de ls fo r lo ng -te rm infra struc ture a nd susta ina b ility o f g ro ups a rising fro m g e no mic me dic ine me e ting s.

F unding Pe r iod and FY14 T

tal:

F Y2011-pre se nt, ro ug hly $80K in F Y14

pic s o f Ge no mic Me dic ine Me e tings 1- 8:

1. Ge no mic Me dic ine I mple me nta tio n in the U.S. (June 2011) 2. F

rming Co lla b o ra tio ns a nd Pilo t Pro je c ts (De c e mb e r 2011)

3. Wo rking with I mple me nta tio n Sta ke ho lde rs (Ma y 2012) 4. Physic ia n E duc a tio n in Ge no mic s (Ja nua ry 2013) 5. Wo rking with F e de ra l Sta ke ho lde rs (Ma y 2013) 6. Glo b a l L e a de rs in Ge no mic Me dic ine (Ja nua ry 2014) 7. Ge no mic Clinic a l De c isio n Suppo rt (Oc to b e r 2014) 8. NHGRI ’ s Ge no mic Me dic ine Po rtfo lio (June 2015)

Majo r Collabo r ations and T he ir Goals:

Na tio na l Ac a de my o f Me dic ine , Ge no mic s Ro undta b le a nd Glo b a l Ge no mic Me dic ine

Co lla b o ra tio n, to pro mo te c ritic a l e va lua tio n a nd sha ring o f a ppro a c he s to imple me nting g e no mic s in c linic a l c a re

Re so ur c e s and T

o ls Pr
duc e d:

1. ClinAc tio n Wo rksho p , De c e mb e r 2011, le a ding to ClinGe n so lic ita tio n a nd pro je c t, http:/ / c linic a lg e no me .o rg / 2. I nte r-So c ie ty Co o rdina ting Co mmitte e fo r Pra c titio ne r E duc a tio n in Ge no mic s, http:/ / www.g e no me .g o v/ 27554614 3. Glo b a l Ge no mic Me dic ine Co lla b o ra tio n (G2MC) in c o lla b o ra tio n with Na tio na l Ac a de my o f Me dic ine , www.io m.e d u/ G2MC 4. Wo rksho p o n Re se a rc h Dire c tio ns in Ge ne tic a lly Me dia te d Ste ve ns Jo hnso n Syndro me / T

E pide rma l Ne c ro lysis, Ma rc h 2015, https:/ / www.g e no me .g o v/ 27560487 , a rising fro m G2MC

F ive Ke y Public atio ns:

1. Ma no lio T A, e t a l. I mple me nting g e no mic me dic ine in the c linic : T he future is he re . Ge ne tic s in Me dic ine 2013; 15:258-67.

SLIDE 27

2. Ra mo s E M, e t a l., Cha ra c te rizing g e ne tic va ria nts fo r c linic a l a c tio n. Ame ric a n Jo urna l o f Me dic a l Ge ne tic s C Se mina rs in Me dic a l Ge ne tic s 2014; 166:93-104.ClinAc tio n 3. Ma no lio T A, Murra y MF, fo r the I nte r-So c ie ty Co o rdina ting Co mmitte e o n Pra c titio ne r E duc a tio n in Ge no mic s.. T he g ro wing ro le o f pro fe ssio na l so c ie tie s in e duc a ting c linic ia ns in g e no mic s. Ge ne tic s in Me dic ine 2014; 16:571-72. 4. Ma no lio T A e t a l., Glo b a l imple me nta tio n o f g e no mic me dic ine : We a re no t a lo ne . Sc ie nc e T ra nsla tio na l Me dic ine , in pre ss.

Majo r Obstac le s o r Ne e ds E nc o unte r e d: Ma jor Obsta c le s or Ne e ds Approa c he s Imple me nte d or Propose d to Ove rc ome Obsta c le s

L a c k o f e vide nc e o f imp a c t o f g e no mic me dic ine imple me nta tio n Pro mo te re se a rc h to fill e vide nc e g a ps L a c k o f re imb urse me nt fo r g e no mic te sting Wo rk with pa ye rs a nd o the r sta ke ho lde rs to ide ntify info rma tio n ne e de d to suppo rt re imb urse me nt Ne e d fo r c linic ia n e duc a tio n a nd g e no mic c linic a l de c isio n suppo rt (CDS) I mple me nt I SCC a nd re se a rc h pro g ra ms to pro vide g e no mic CDS Re stric tive re g ula to ry po lic ie s po o rly a da pte d to dyna mic na ture a nd sc a le o f g e no mic inte rve ntio ns Wo rk with fe de ra l a g e nc ie s to impro ve unde rsta nding a nd pro vide ne e de d e vide nc e Ne e d fo r b e dside b a c k to b e nc h re se a rc h pipe line fo r unde rsta nding g e no mic func tio n a nd furthe r a pplic a tio ns Pro mo te c o lla b o ra tio ns a mo ng b a sic a nd a pplie d pro g ra ms, suc h a s this GM8 me e ting

NHG RI E x Offic io Staff: E

ric Gre e n, T e ri Ma no lio , L a ura Ro drig ue z

SLIDE 28

Ge no mic Me dic ine VIII – Summar y o f F

c us Pr
gr

am IGNIT E

Pro g ram Name and We b site : I mple me nting Ge no mic s in Pra c tic e (I GNI T E ) Ne two rk, http:/ / www.ig nite - g e no mic s.o rg / PI s and Funde d Site s: E rwin Bo tting e r, Ca ro l Ho ro witz I c a hn Sc ho o l o f Me dic ine a t Mo unt Sina i Jo sh De nny, Mia L e vy Va nde rb ilt Unive rsity Da ve F lo c kha rt, Pa ul De xte r I ndia na Unive rsity Ge o ff Ginsb urg Duke Unive rsity Julie Jo hnso n Unive rsity o f F lo rida T

ni Po llin

Unive rsity o f Ma ryla nd a t Ba ltimo re Ste ve K imme l Unive rsity o f Pe nnsylva nia (Co o rdina ting Ce nte r)

Obje c tive s:

1. De ve lo p me tho d s fo r a nd e va lua te fe a sib ility o f inc o rp o ra ting a n ind ivid ua l’ s g e no mic info rma tio n

into his o r he r c linic a l c a re .

2. Inte g ra te g e no mic info rma tio n into the e le c tro nic me d ic a l re c o rd (EMR) a nd p ro vid e c linic a l

d e c isio n sup p o rt (C DS) fo r imp le me nta tio n o f a p p ro p ria te inte rve ntio ns o r c linic a l a d vic e .

3. C o ntrib ute to the e vid e nc e b a se re g a rd ing o utc o me s o f inc o rp o ra ting g e no mic info rma tio n into

c linic a l c a re .

4. De fine a nd sha re the pro c e sse s o f g e no mic me dic ine imple me nta tio n, diffusio n, a nd susta ina b ility in

dive rse se tting s.

F unding Pe r iod and FY14 T

tal:

F Y2013-F Y2017, $5.7M in FY14

Cur r e nt Intr a-Pr

am Wo r king Gr

ups:
1. Co mmo n Me a sure s
2. Disse mina tio n, Outre a c h, E

c o no mic s, a nd Susta ina b ility (DOE S)

3. E

duc a tio n

4. Pro vide r a nd Pa ye r Ad o p tio n (PPA)
5. Clinic a l De c isio n Suppo rt (CDS)
6. Clinic a l Va lidity a nd Utility (CVU)
7. Pha rma c o g e ne tic s (PGx)
8. Pub lic a tio ns

Major Collabo r ations and T he ir Goals:

e ME

RGE : sha re me tho ds fo r imple me nta tio n o f g e no mic me dic ine a nd c linic a l de c isio n suppo rt

CYP2C19/ Clo pido g re l: p e rfo rm multi-c e nte r a na lysis o f o utc o me s o f CYP2C19 te sting fo r c lo pido g re l

Re so ur c e s and T

o ls Pr
duc e d: No ne to da te

F ive Ke y Public atio ns: 1.

K imme l, S. e t a l., T

he Imple me nting G e nomic s in Pra c tic e Ne twork (IGNIT E ): A Coordina te d Effort to Study a nd Improve Imple me nta tion of Ge nomic s in Clinic a l Pra c tic e . Po ste r pre se nta tio n a t the

Ame ric a n So c ie ty fo r Huma n Ge ne tic s Annua l Me e ting , Sa n Die g o C A, Oc to b e r 2014.

L e vy, K e t a l., Pre re q uisite s to I mple me nting a Pha rma c o g e no mic s Pro g ra m in a L a rg e He a lth- Ca re Syste m. Clinic a l Pha rma c o lo g y & T he ra pe utic s 2014; 96:307-309.

Ginsb urg , G. Me dic a l G e nomic s: Ga the r a nd use g e ne tic da ta in he a lth c a re . Na ture 2014; 508:451-3.

Orla ndo , L . e t a l., I mple me nting fa mily he a lth histo ry risk stra tific a tio n in prima ry c a re : I mpa c t o f g uide line c rite ria o n po pula tio ns a nd re so urc e de ma nd. Ame ric a n Jo urna l o f Me dic a l Ge ne tic s Pa rt C: Se mina rs in Me dic a l Ge ne tic s 2014; 166:24-33.

SLIDE 29

We itze l, K. e t a l., Clinic a l pha rma c og e ne tic s imple me nta tion: Approa c he s, suc c e sse s, a nd

c ha lle ng e s. Ame ric a n Journa l of Me dic a l G e ne tic s Pa rt C: Se mina rs in Me dic a l Ge ne tic s 2014;

166:56-67.

Majo r Obstac le s o r Ne e ds E nc o unte r e d: Ma jor Obsta c le s or Ne e ds Approa c he s Imple me nte d/ Propose d to O ve rc ome Obsta c le s

Cha ng ing E HRs Ob ta in sub sta ntia l E HR te a m a nd re so urc e c o mmitme nt; purc ha se a dditio na l mo dule s o r b uild ne w pro g ra mming to suppo rt HL 7 c o nne c tio ns with ne w E HR syste m Site dive rsity – the sa me pro to c o l do e sn’ t wo rk fo r a ll site s De ve lo p diffe re nt pro to c o ls de pe nding o n the wo rkflo w o f the site Sc a la b ility a nd susta ina b ility o f g e no mic me dic ine Wo rk with pa ye rs to g e t re imb urse me nt fo r g e ne tic te sting Diffe ring e duc a tio n a nd tra ining ne e ds fo r sub g ro ups o f pro fe ssio na ls invo lve d in c linic a l imple me nta tio n; ro ta ting sta ff De ve lo p diffe re nt tra ining mo d ule s; c o ntinuo us e duc a tio n T urna ro und time fo r g e no mic re sults Pe rfo rm pro spe c tive g e no typing , b a se d o n risk c a lc ula tio ns CMS/ third pa rty pa ye rs suppo rt o f PGx a nd disc re te te sting ve rsus PGx pa ne ls Sub mit Curre nt Pro c e d ura l T e rmino lo g y (CPT ) Co d ing Cha ng e Re q ue st to the Ame ric a n Me dic a l Asso c ia tio n (AMA) fo r po lypha rma c y pha rma c o g e no mic s se q ue nc e a na lysis pa ne ls Cha ng e s in e vide nc e a nd thus c ha ng e s in tre a tme nt Upda te c linic a l de c isio n suppo rt b a se d o n ne w c linic a l a dviso rie s De ve lo ping a pplic a b le a nd use ful CDS la ng ua g e tha t will b e use d in diffe re nt c linic a l sc e na rio s De ve lo pe d CDS wo rking g ro up to disc uss a nd impro ve institutio na l CDS stra te g ie s b a se d o n c linic a l sc e na rio Mig ra tio n to ne w mo le c ula r te sting pa ne ls re q uire s infra struc ture e vo lutio n Co ntinuo us ite ra tive impro ve me nt in g e no mic re sults re pre se nta tio n a nd o ppo rtunity to re -e va lua te e me rg ing sta nda rds fo r g e no mic he a lth info rma tio n

NHG RI Pr

am Offic ials: E

b o ny Ma dde n, He a the r Junkins

SLIDE 30

Ge no mic Me dic ine VIII – Summar y o f F

c us Pr
gr

am INSIGHT

Pro g ram Name and We b site : Ne wb o rn Se q ue nc ing I n Ge no mic me dic ine a nd pub lic He a lT h (NSI GHT ), http:/ / www.g e no me .g o v/ 27558493 PI s and Funde d Site s:

Princ ipa l Inve stig a tor Institution T itle

Ro b e rt Gre e n a nd Ala n Be g g s Brig ha m a nd Wo me n’ s Ho spita l Ge no me Se q ue nc e -Ba se d Sc re e ning fo r Childho o d Risk a nd Ne wb o rn I llne ss Ste phe n K ing smo re Childre n’ s Me rc y Ho spita l Clinic a l a nd So c ia l I mplic a tio ns o f 2-da y Ge no me Re sults in Ac ute ly I ll Ne wb o rns Ste ve n Bre nne r, Ba rb a ra K

e nig , Puiya n K

wo k, Je nnife r Puc k Unive rsity o f Ca lifo rnia , Sa n F ra nc isc o Se q ue nc ing o f Ne wb o rn Blo o d Sp o t DNA to I mpro ve a nd E xpa nd Ne wb o rn Sc re e ning Cynthia Po we ll a nd Jo na tha n Be rg Unive rsity o f No rth Ca ro lina a t Cha pe l Hill NC NE XUS, No rth Ca ro lina Ne wb o rn E xo me Se q ue nc ing fo r Unive rsa l Sc re e ning

Obje c tive s:

1. Ac q uisitio n a nd a na lysis o f g e no mic da ta se ts tha t e xpa nd c o nside ra b ly the sc a le o f da ta a va ila b le fo r a na lysis in the ne wb o rn pe rio d. 2. Pe rfo rm c linic a l re se a rc h tha t will a dva nc e unde rsta nding o f spe c ific diso rde rs ide ntifia b le via ne wb o rn sc re e ning thro ug h pro mising ne w DNA-b a se d a na lysis 3. Co nd uc t re se a rc h re la te d to the e thic a l, le g a l a nd so c ia l implic a tio ns (E L SI ) o f the po ssib le imple me nta tio n o f g e no mic se q ue nc ing o f ne wb o rns

F unding Pe r iod and FY14 T

tal:

F Y2013-F Y2017, $4.73 in FY14 ($2.366M e a c h fro m NHGRI a nd NI CHD) So urc e F Y13 F Y14 F Y15 F Y16 F Y17 T

ta l

NHGRI $2.355M $2.366M $2.365M $2.361M $2.368M $11.815M NI CHD $2.355M $2.366M $2.365M $2.361M $2.368M $11.815M T OT AL $4.71M $4.73M $4.73M $4.72M $4.74M $23.63M

Cur r e nt Intr a-Pr

am Wo r king Gr

ups:

1. Co mmo n Da ta E le me nts (CDE ) 2. E thic a l, L e g a l a nd So c ia l I mplic a tio ns (E L SI )

Majo r Collabo r ations and T he ir Goals: No ne to d a te Re so ur c e s and T

o ls Pr
duc e d: No ne to da te

F ive Ke y Public atio ns: No ne to da te Majo r Obstac le s o r Ne e ds E nc o unte r e d: Ma jor Obsta c le s or Ne e ds Approa c he s Imple me nte d/ Propose d to Ove rc ome Obsta c le s

Re g ula tio n a ro und re turn o f g e no mic da ta to pa rtic ipa nts NHGRI in disc ussio ns with the F DA Cre a tio n o f Co mmo n Da ta E le me nt lists Da ta b a se o f e le me nts fo r studie s to use a c ro ss NHGRI

r NI

NHG RI Pr

am Offic ials: Ana sta sia Wise , T

iina Urv (NI CHD), Jo y Bo ye r, L uc ia Hindo rff, Je ffe ry Sc hlo ss, L u Wa ng

SLIDE 31

Ge no mic Me dic ine VIII – Summar y o f F

c us Pr
gr

am UDN

Pro g ram Name : Undia g no se d Dise a se Ne two rk, https:/ / c o mmo nfund .nih.g o v/ Dise a se s/ inde x

PIs and F unde d Site s: Coordina ting Ce nte r

Za k K

ha ne , Ra c he l Ra mo ni, a nd Ale xa Mc Cra y

Ha rva rd Me dic a l Sc ho o l

Se que nc ing Core s

Christine E ng Ba ylo r Co lle g e o f Me dic ine Ho wa rd Ja c o b Me dic a l Co lle g e o f Wisc o nsin w/ I llumina

Clinic a l Site s

Bre nda n L e e Ba ylo r Co lle g e o f Me dic ine Va nda na Sha shi a nd Da vid Go ldste in Duke Unive rsity w/ Co lumb ia Unive rsity Jo se ph L

sc a lzo

Ha rva rd T e a c hing Ho spita ls (inc luding Bo sto n Childre n’ s Ho spita l, Brig ha m a nd Wo me n’ s Ho spita l a nd Ma ssa c huse tts Ge ne ra l) E ua n Ashle y, Jo na tha n Be rnste in a nd Pa ul Gra ha m F ishe r Sta nfo rd Unive rsity E ric Vila in, K a trina Dipple , Sta nle y Ne lso n a nd Christina Pa lme r Unive rsity o f Ca lifo rnia , L

s Ang e le s

Jo hn Phillips a nd Jo hn Ne wma n Va nde rb ilt Unive rsity Me dic a l Ce nte r

Obje c tive s:

1. I mpro ve the le ve l o f dia g no sis a nd c a re fo r pa tie nts with undia g no se d dise a se s thro ug h c o mmo n pro to c o ls de sig ne d b y a la rg e c o mmunity o f inve stig a to rs 2. F a c ilita te re se a rc h into the e tio lo g y o f undia g no se d dise a se s b y c o lle c ting a nd sha ring hig h q ua lity c linic a l a nd la b o ra to ry da ta . 3. Cre a te a n inte g ra te d a nd c o lla b o ra te c o mmunity a c ro ss c linic a l site s a nd a mo ng la b o ra to ry a nd c linic a l inve stig a to rs.

F unding Pe r iod and FY14 T

tal: F

Y2013-F Y2017: F Y14 to ta l $19.6 M

Cur r e nt Intr a-Pr

am Wo r king Gr

ups:

1. Billing Wo rking Gro up 2. Bio re po sito ry a nd Bio spe c ime n Wo rking Gro up 3. Clinic a l Pro to c o ls Wo rking Gro up 4. E c o no mic s Wo rking Gro up 5. Ge ne tic Co unse ling & T e sting Wo rking Gro up 6. Se q ue nc ing Wo rking Gro up 7. T e c hno lo g y Wo rking Gro up

Majo r Collabo r ations and T he ir Goals: No ne to d a te Re so ur c e s and T

o ls Pr
duc e d: No ne to da te

F ive Ke y Public atio ns: No ne to da te Majo r Obstac le s and Ne e ds that Might be F ac ilitate d by G e no mic Me dic ine Re se ar c h: Ma jor Obsta c le s a nd Ne e ds Approa c he s Conside re d or Propose d to O ve rc ome Obsta c le s

E sta b lishme nt o f a Ce ntra l I RB L a ng ua g e in FOAs, c e ntra l I RB spe c ifie d up fro nt Sha ring o f ide ntifia b le da ta De ve lo pme nt o f la ng ua g e to sha re with c o mmunity F I SMA c o mplia nc e L a ng ua g e in FOAs, c le a r pa th fo r initia tive s with intra mura l c o mpo ne nts Re g ula tio n a ro und re turn o f g e no mic da ta to pa rtic ipa nts NHGRI in disc ussio ns with the F DA Ma tc hing pa tie nts to the mse lve s Co nside ring use o f GUI D

NHG RI Pr

am Offic ials: Ana sta sia Wise

SLIDE 32

RE L AT E D PROGRAMS

SLIDE 33

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am AF MS

Pro g ram Name and We b site : AF MS Pe rso na lize d Me dic ine Pro g ra m https:/ / kx2.a fms.mil/ kj/ kx2/ PC2ZGe no mic Me dic ine / Pa g e s/ ho me .a spx PI s and Funde d Site s:

Intra mura l Colla bora tors

De b ra Nie me ye r USAF 59th Me dic a l Wing Co l Mic ha e l Grinke me ye r USAF 711th Huma n Pe rfo rma nc e Wing Ca pt Ma uric io De Ca stro USAF 81st Me dic a l Gro up Zyg munt Ga ldzic ki Unifo rme d Se rvic e s Unive rsity o f the He a lth Sc ie nc e s

E xtra mura l Colla bora tors

Mic ha e l Christma n Co rie ll I nstitute De e pa k Vo o ra Duke Unive rsity Alliso n Vo rde stra sse Duke Unive rsity Andre w De wa n Ya le Unive rsity

Unive rsity Affilia te d Re se a rc h Ce nte r (UARC)

Ruth Vo g e l Jo hns Ho pkins Applie d Physic s L a b Chris Bra db urne Jo hns Ho pkins Applie d Physic s L a b L uc y Ca rruth Jo hns Ho pkins Applie d Physic s L a b Ba rt Pa ulha mus Jo hns Ho pkins Applie d Physic s L a b

Obje c tive s:

1. De ve lo p/ fa c ilita te ne c e ssa ry infra struc ture a nd e nviro nme nt fo r the de ve lo pme nt o f pe rso na lize d me dic ine within the AF MS 2. Ha rve st info rma tio n o n the me dic a l a pplic a tio n o f g e no mic me dic ine , a s we ll a s de te rmine Air F

rc e re le va nc y fo r furthe r inve stig a tio n

3. T ra nsla te g e no mic disc o ve rie s into ne w c linic a l pra c tic e s fo r Airme n a nd the ir b e ne fic ia rie s 4. Ad dre ss e d uc a tio na l g a ps fo r pa tie nts a nd pro vide rs 5. De te rmine the c linic a l va lue o f utilizing g e ne tic risk info rma tio n in pa tie nt c a re

F unding Pe r iod and FY14 T

tal:

F Y2011-F Y2018, re ne wa l unde r c o nside ra tio n: F Y14 to ta l $14.8M

Cur r e nt Intr a-Pr

am Wo r king Gr

ups:

1. Pre c isio n Ca re Ad viso ry Pa ne l (PCAP)

Pro vide s re c o mme nda tio ns o n the a dva nc e me nt o f pe rso na lize d me dic ine b y b ring ing

to g e the r a b ro a dly-de ve lo pe d a nd e ng a g e d c o a litio n o f re se a rc he rs, c linic ia ns, e d uc a to rs, c o unse lo rs, a nd p o lic y sp e c ia lists.

Pro vide s po lic y, sc ie ntific , a nd o pe ra tio na l re c o mme nda tio ns a nd a ppro a c he s fo r the Milita ry

He a lth Syste m in c o nc e rt with fe de ra l e ffo rts to sup po rt c linic a l g e ne tic sc re e ning , c o unse ling , a nd he a lth c a re se rvic e s fo r Se rvic e Me mb e rs a nd b e ne fic ia rie s. 2. Ge no mic Re se a rc h Wo rking Gro up (GRWG)

GRWG b ring s to g e the r Air F
rc e Ge no mic s Re se a rc he rs to disc uss c urre nt a nd future re se a rc h

pro je c ts.

Curre nt GRWG me mb e rship inc lude s:
AFMSA/ SG5P Re se a rc h a nd I

nno va tio ns

USAF

59th Me dic a l Wing

USAF

711th Huma n Pe rfo rma nc e Wing

USAF

81st Me dic a l Gro up

SLIDE 34

3. Ce nte r fo r Clinic a l L a b o ra to ry Me dic ine (CCL M) within the De fe nse He a lth Ag e nc y d e ve lo ps Clinic a l L a b o ra to ry I mpro ve me nt Ame ndme nts (CL IA) c o mpa ra b le re g ula tio ns a nd a dministe rs the Clinic a l L a b o ra to ry I mpro ve me nt Pro g ra m (CL I P); AF MS p a rtic ipa tio n is within the L a b Jo int Wo rking Gro up 4. Pro vide r E d uc a tio n Pa ne l de sig ns e d uc a tio na l re so urc e s fo r Milita ry He a lth Syste m (MHS) he a lthc a re pro vide rs

Majo r Collabo r ations and T he ir Goals:

1. E le c tro nic Me dic a l Re c o rds a nd Ge no mic s (e ME RGE ) Ne two rk: https:/ / e me rg e .mc .va nde rb ilt.e du/ 2. I mple me nta tio n, Ad o ptio n, a nd Utility o f F a mily Histo ry in Dive rse Ca re Se tting s: http:/ / www.ig nite - g e no mic s.o rg / ig nite _duke .html

Re so ur c e s and T

o ls Pr
duc e d:

1. Re q uire me nts ha ve b e e n e sta b lishe d fo r the AF MS Dig ita l Bio b a nk. A pro to type is c urre ntly in de ve lo pme nt; pro to type c o mple tio n is sc he dule d fo r 2016. 2. Co nside ra tio n o f te le g e ne tic s re so urc e to e nsure the ne c e ssa ry to o ls a nd re so urc e s a re ma de a va ila b le to pa tie nts a nd pro vide rs.

F ive Ke y Public atio ns:

1. Dise a ti L . e t al (2015). Co mmo n Ge ne tic Risk fo r Me la no ma E nc o ura g e s Pre ve ntive Be ha vio r Cha ng e . J Pe rs Me d . 2015 F e b 17;5(1):36-49. d o i: 10.3390/ jpm5010036.

SLIDE 35

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am CMG

Pro g ram Name and We b site : Ce nte rs fo r Me nde lia n Ge no mic s, http:/ / www.me nde lia n.o rg / PI s and Funde d Site s (U-Grants and Co o rdinating Ce nte r) Ric ha rd L ifto n (c o nta c t PI ), Mura t Gune l, Ma rk Ge rste in, Shrika nt Ma ne Ya le Unive rsity Ce nte r fo r Me nde lia n Ge no mic s (YCMG) Da vid Va lle (c o nta c t PI ), Jim L upski Ba ylo r-Ho pkins Ce nte r fo r Me nde lia n Ge no mic s (BHCMG) De b o ra h Nic ke rso n (c o nta c t PI ), Mic ha e l Ba msha d, Ja y She ndure Unive rsity o f Wa shing to n Ce nte r fo r Me nde lia n Ge no mic s (UWCMG), Co o rdina ting Ce nte r o f Ce nte rs fo r Me nde lia n Ge no mic s

Obje c tive s:

1. Disc o ve r a s ma ny “c a usa l g e ne s” fo r Me nde lia n diso rde rs a s po ssib le a t the funde d c e nte rs
2. I

mpro ve suc c e ss ra te s, c o sts, a nd e ffic ie nc y fo r c a usa l g e ne disc o ve ry

3. E

na b le o the rs to disc o ve r mo re c a usa l g e ne s thro ug h re so urc e sha ring

4. Co o rdina te with o the r re se a rc he rs a nd pro g ra ms wo rldwide o n diso rde rs to b e studie d a nd re so urc e

de ve lo pme nt

F unding Pe r iod and FY14 T

tal: (U gr

ants only) - F

Y2012-F

Y2019. $9.48M HG a nd $1.97M HL

in F Y14

Cur r e nt Intr a-Pr

am Wo r king Gr

ups:
Co mmunity E

ng a g e me nt/ I nq uiry Re sp o nse

Re g ula to ry Re vie w
Da ta Ana lysis/ Da ta Re le a se
Phe no type Re vie w
“So lve ” Ra te
Ra pid Pub lic a tio n

Majo r Collabo r ations and T he ir Goals:

Ge no me Se q ue nc ing Pro g ra m (L

SAC/ CMG/ GS-I T ): jo int me e ting s in 2012-2013

GA2GH - Ma tc hma ke r E

xc ha ng e fo r pro je c t c o o rdina tio n

Re so ur c e s and T

o ls Pr
duc e d (r

e pr e se ntative sample ):

1. phe no DB (https:/ / phe no db .o rg / ) 2. Ge ne Ma tc he r (https:/ / g e ne ma tc he r.o rg / ) 3. AL OF T (https:/ / www.g ithub .c o m/ g e rste inla b / a lo ft) 4. Me nde lia n Phe no type Va ria nt Co mpa riso n T

o l: http:/ / mpvc t.g s.wa shing to n.e du

5. PRI MUS (Pe dig re e Re c o nstruc tio n a nd I de ntific a tio n o f a Ma xima lly Unre la te d Se t (https:/ / primus.g s.wa shing to n.e d u/ primuswe b / ) 6. Se q ue nc e da ta se ts in db Ga P (https:/ / www.nc b i.nlm.nih.g o v/ g a p) 7. Ca usa l va ria nt info rma tio n in ClinVa r (http:/ / www.nc b i.nlm.nih.g o v/ c linva r/ ; to b e sc a le d up )

F ive Ke y Public ations (fr

m >170 public atio ns):

1. Ba msha d MJ, e t a l. T he Ce nte rs fo r Me nde lia n Ge no mic s: A ne w la rg e -sc a le initia tive to ide ntify the g e ne s unde rlying ra re Me nde lia n c o nditio ns. AJMG. 2012. PMI D: 22628075

Majo r Obstac le s o r Ne e ds E nc o unte r e d: Ma jor Ne e ds Approa c he s Imple me nte d/ to be Imple me nte d to Me e t the Ne e ds

Wo rldwide a sc e rta inme nt a nd phe no typic c ha ra c te riza tio n o f fa milie s with Me nde lia n c o nditio ns Co ntinuo us so lic ita tio n e ffo rts; phe no DB fo r c o lle c tio n, sto ra g e , a nd a na lysis o f phe no typic fe a ture s; Pro je c t Co o rdina tio n (e .g ., Ma tc hma ke r E xc ha ng e ) I mpro ve me nt o f suc c e ss ra te s fo r disc o ve ring c a usa l g e ne s/ va ria nts I mpro ve me nt o f study de sig ns; I mpro ve me nt o f se q ue nc ing q ua lity a nd c o sts; I mpro ve me nt o f a na lysis me tho ds; Pro je c t c o o rdina tio n

SLIDE 36

Ma ximizing the a c c e ssib ility a nd use fulne ss o f pub lic a lly re le a se d g e no mic da ta Sub mitting c a usa l va ria nt info rma tio n to ClinVa r; Re le a se a lle le fre q ue nc ie s a nd a sso c ia te d hig h le ve l phe no type info rma tio n fo r e a sy a c c e ss (pilo t e ffo rt o ng o ing ) Ra pid pub lic a tio n o f re se a rc h re sults o n pe e re d- re vie we d jo urna ls E sta b lishing minimum pub lic a tio n re q uire me nt with jo urna ls (e xplo ra to ry sta g e )

NHG RI Pr

am Offic ials: L

u Wa ng (DGSc i), Chris We lling to n (DGSc i), Nic o le L

c kha rt (DG&S)

SLIDE 37

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am CPIC

am Name and We b site : Clinic a l Pha rma c o g e ne tic s I

mple me nta tio n Co nso rtium (CPI C), https:/ / www.pha rmg kb .o rg / pa g e / c pic

PIs and F unde d Site s:

Ma ry Re lling

St. Jude Childre n’ s Re se a rc h Ho spita l

T e ri K le in Sta nfo rd Unive rsity

Obje c tive s:

T he g o a l o f the Clinic a l Pha rma c o g e ne tic s I mple me nta tio n Co nso rtium (CPI C) is to a c c e le ra te imple me nta tio n o f re se a rc h disc o ve rie s in pha rma c o g e no mic s into the c linic . A ke y a ssumptio n o f CPI C is tha t the g e ne tic te st re sults a re a lre a dy a va ila b le . CPI C do e s no t ta ke a po sitio n o n whe n te sts sho uld b e o rde re d , b ut ra the r ho w the y sho uld b e use d . 1. Cre a te , c ura te , a nd upd a te CPI C g e ne / drug g uide line s fo r a ll g e ne / drug g ro uping s tha t a re c linic a lly a c tio na b le ; e xpa nd the g uide line s to inc lude de finitive c linic a l re c o mme nda tio ns fo r no n-a c tio na b le drug s linke d to o the rwise a c tio na b le g e ne s.

fre e ly a va ila b le , pe e r-re vie we d, upda ta b le g uide line s
inc lude c o mpre he nsive ta b le s to tra nsla te g e no type info rma tio n to phe no type to fa c ilita te
c linic a l de c isio n suppo rt (CDS) in e le c tro nic he a lth re c o rds (E

HRs) 2. E nha nc e a c c e ss to a nd input into g uide line s b y e xte rna l g ro ups suc h a s NI H’ s Pha rma c o g e no mic s Re se a rc h Ne two rk, NI H’ s Ge no mic Me dic ine Wo rking g ro up , AHRQ’ s www.g uide line s.g o v, NI H’ s Ge ne tic T e st Re g istry, Pub Me d , F DA, ClinGe n, I OM’ s Ge no mic Me dic ine Ro undta b le , pro fe ssio na l so c ie tie s, a nd E HR ve nd o rs b y syste ma tic a lly e va lua ting c o mmunity usa g e o f CPI C g uide line s o n a q ua ntita tive , q ua lita tive , a nd o ng o ing b a sis to re spo nd to the c o mmunity a nd ma ke e nha nc e me nts a s ne e de d .

F unding Pe r iod and FY14 T

tal:

F Y2012-F Y2015, re ne wa l unde r c o nside ra tio n: F Y14 to ta l $410,000/ ye a r dire c t

Cur r e nt Intr a-Pr

am Wo r king Gr

ups:
CPI

C I nfo rma tic s Wo rking Gro up https:/ / www.pha rmg kb .o rg / pa g e / c pic I nfo rma tic s

C Ste e ring Co mmitte e https:/ / www.pha rmg kb .o rg / pa g e / c pic

Majo r Collabo r ations and T he ir Goals:

Pha rmGK

B (www.pha rmg kb .o rg )

NHGRI

’ s Ge no mic Me dic ine Wo rking g ro up http:/ / www.g e no me .g o v/ 27549220

AHRQ’ s Na tio na l Guide line s Cle a ring ho use www.g uide line s.g o v
NCBI

’ s Ge ne tic T e st Re g istry http:/ / www.nc b i.nlm.nih.g o v/ g tr/

ClinGe n’ s Pha rma c o g e no mic Do ma in Wo rking Gro up http:/ / www.c linic a lg e no me .o rg / a b o ut/ wo rking -g ro ups/
I

OM’ s Ro undta b le o n T ra nsla ting Ge no mic -Ba se d Re se a rc h fo r He a lth https:/ / www.io m.e d u/ Ac tivitie s/ Re se a rc h/ Ge no mic Ba se dRe se a rc h.a spx

ASHP http:/ / www.a shp.o rg / me nu/ Pra c tic e Po lic y/ Po lic yPo sitio nsGuide line sBe stPra c tic e s/

Bro wse b yDo c ume ntT ype / E ndo rse dDo c ume nts.a spx

Ge ne tic s/ g e no mic s Co mpe te nc y Ce nte r http:/ / g -2-c -2.o rg / /
E

me rg e -PGx http:/ / www.g e no me .g o v/ 27540473 (info rma l c o nne c tio ns thro ug h CPI C I nfo rma tic s Wo rking Gro up;

Re so ur c e s and T

o ls Pr
duc e d:

1. CPI C g uide line s https:/ / www.pha rmg kb .o rg / vie w/ do sing -g uide line s.do ? so urc e =CPI C 2. Ge ne / drug list https:/ / www.pha rmg kb .o rg / c pic / pa irs 3. L ist o f pha rma c o g e ne tic va ria nts https:/ / www.pha rmg kb .o rg / c pic / a lle le s 4. CPI C T e rm Sta nda rdiza tio n fo r Clinic a l Pha rma c o g e ne tic T e st Re sults Pro je c t https:/ / www.pha rmg kb .o rg / pa g e / c pic T e rmPro je c t

F ive Ke y Public atio ns:

1. Ca udle K E , K le in T E , Ho ffma n JM, Mulle r DJ, Whirl-Ca rrillo M, Go ng L , Mc Do na g h E M, Sa ng kuhl K, T ho rn CF, Sc hwa b M, Ag und e z JA, F re imuth RR, Huse r V, L e e MT , I wuc hukwu OF, Cre ws K R, Sc o tt SA, Wa de lius M, Swe n JJ, T ynda le RF, Ste in CM, Ro de n D, Re lling MV, Willia ms MS, Jo hnso n SG. I nc o rpo ra tio n o f pha rma c o g e no mic s into

SLIDE 38

ro utine c linic a l pra c tic e : the Clinic a l Pha rma c o g e ne tic s I mple me nta tio n Co nso rtium (CPI C) g uide line de ve lo pme nt pro c e ss. Curre nt drug me ta b o lism. 2014;15(2):209-17. Pub Me d PMI D: 24479687 2. Re lling MV, K le in T E . CPI C: Clinic a l Pha rma c o g e ne tic s I mple me nta tio n Co nso rtium o f the Pha rma c o g e no mic s Re se a rc h Ne two rk. Clinic a l pha rma c o lo g y a nd the ra pe utic s. 2011;89(3):464-7. PMI D: 21270786 3. Re lling MV, Ga rdne r E E , Sa ndb o rn WJ, Sc hmie g e lo w K , Pui CH, Ye e SW, Ste in CM, Ca rrillo M, E va ns WE , K le in T E, Clinic a l Pha rma c o g e ne tic s I mple me nta tio n C. Clinic a l Pha rma c o g e ne tic s I mple me nta tio n Co nso rtium g uide line s fo r thio purine me thyltra nsfe ra se g e no type a nd thio purine do sing . Clinic a l pha rma c o lo g y a nd the ra pe utic s. 2011;89(3):387-91. Pub Me d PMI D: 21270794 4. Sc o tt SA, Sa ng kuhl K, Ste in CM, Hulo t JS, Me g a JL , Ro de n DM, K le in T E, Sa b a tine MS, Jo hnso n JA, Shuldine r AR, Clinic a l Pha rma c o g e ne tic s I mple me nta tio n C. Clinic a l Pha rma c o g e ne tic s I mple me nta tio n Co nso rtium g uide line s fo r CYP2C19 g e no type a nd c lo pido g re l the ra py: 2013 upda te . Clinic a l pha rma c o lo g y a nd the ra pe utic s. 2013;94(3):317-23. PMI D: 23698643 5. Jo hnso n JA, Go ng L , Whirl-Ca rrillo M, Ga g e BF, Sc o tt SA, Ste in CM, And e rso n JL , K imme l SE , L e e MT , Pirmo ha me d M, Wa de lius M, K le in T E, Altma n RB, Clinic a l Pha rma c o g e ne tic s I mple me nta tio n C. Clinic a l Pha rma c o g e ne tic s I mple me nta tio n Co nso rtium Guide line s fo r CYP2C9 a nd VK ORC1 g e no type s a nd wa rfa rin do sing . Clinic a l pha rma c o lo g y a nd the ra pe utic s. 2011;90(4):625-9. Pub Me d PMI D: 21900891

Majo r Obstac le s and Ne e ds that Might be F ac ilitate d by G e no mic Me dic ine Re se ar c h: Ma jor Obsta c le s a nd Ne e ds Approa c he s Conside re d or Propose d to O ve rc ome Obsta c le s

L a c k o f sta nda rdiza tio n o f te st re sults hinde ring E HR ve ndo r-re a dy so lutio ns CPI C T e rm Sta nda rdiza tio n fo r Clinic a l Pha rma c o g e ne tic T e st Re sults Pro je c t L imite d se t o f use c a se s fo r g e no mic c linic a l de c isio n suppo rt (CDS) CPI C pro vide s ve nd o r a g no stic re so urc e s to fa c ilita te imple me nta tio n o f CDS in E HRs

NIH Pr

am Offic ials: Ro c he lle L

ng (NI

GMS); T e ri Ma no lio (NHGRI )

SLIDE 39

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am E NCODE

am Name and We b site : E

nc yc lo pe dia o f DNA E le me nts (E NCODE) Pro je c t We b site : https:/ / www.e nc o de pro je c t.o rg / NHGRI We b site : https:/ / www.g e no me .g o v/ e nc o de / PI s and Funde d Site s:

Produc tion Ce nte rs

Bra dle y Be rnste in Bro a d I nstitute o f MI T a nd Ha rva rd T ho ma s Ging e ra s Co ld Spring Ha rb o r L a b o ra to ry Bre nto n Gra ve le y Unive rsity o f Co nne c tic ut He a lth Ce nte r Ric ha rd Mye rs Hudso nAlpha I nstitute fo r Bio te c hno lo g y Bing Re n L I CR/ Unive rsity o f Ca lifo rnia , Sa n Die g o Mic ha e l Snyde r Sta nfo rd Unive rsity Jo hn Sta ma to ya nno p o ulo s Unive rsity o f Wa shing to n, Se a ttle

Da ta Ce nte rs

Mic ha e l Che rry Sta nfo rd Unive rsity Zhiping We ng Unive rsity o f Ma ssa c huse tts Me dic a l Sc ho o l

Computa tiona l Ana lysis

Pe te r Bic ke l Unive rsity o f Ca lifo rnia Da vid Giffo rd Ma ssa c huse tts I nstitute o f T e c hno lo g y Sund uz K e le s Unive rsity o f Wisc o nsin, Ma diso n Ro b e rt K le in Mo unt Sina i Sc ho o l o f Me dic ine Jo na tha n Pritc ha rd Sta nfo rd Unive rsity Xinshu Xia o Unive rsity o f Ca lifo rnia , L

s Ang e le s

Obje c tive s:

1. I

de ntify a ll o f the c a ndida te func tio na l e le me nts in the huma n a nd mo use g e no me s b y e mplo ying hig h- thro ug hput, g e no me -wide e xpe rime nta l a nd c o mputa tio na l me tho ds

2. Ma ke the c a ta lo g o f c a ndida te func tio na l e le me nts fre e ly a va ila b le to the b io me dic a l c o mmunity
3. I

mple me nt sta nda rds to e nsure hig h-q ua lity da ta a nd de ve lo p no ve l a lg o rithms to fa c ilita te a na lysis

4. I

mpro ve hig h-thro ug hput me tho ds to ide ntify func tio na l e le me nts

5. De ve lo p ne w me tho ds to impro ve inte rpre ta tio n a nd a na lysis o f ENCODE

da ta

6. Co mb ine E

NCODE da ta with re la te d func tio na l da ta fro m o the r pro je c ts to drive ne w b io lo g ic a l insig hts

7. Use E

NCODE da ta to impro ve o n the a na lysis o f dise a se ma pping studie s to ide ntify c a usa l va ria nts

F unding Pe r iod and FY14 T

tal: F

Y2003-F Y2015, re ne wa l unde r c o nside ra tio n: F Y14 to ta l $26.2M

Cur r e nt Intr a-Pr

am Wo r king Gr

ups:
1. Ana lysis Wo rking Gro up

1.1 E NCODE a nd GWAS Wo rking Gro up 1.2 E NCODE a nd Ca nc e r Wo rking Gro up 1.3 3D Nuc le o me Wo rking Gro up 1.4 Re g ula tio n Wo rking Gro up

2. Huma n Re so urc e s Wo rking Gro up
3. Mo use Wo rking Gro up
4. Da ta Re le a se a nd Pub lic a tio ns Wo rking Gro up
5. Outre a c h Wo rking Gro up
6. F

unc tio na l Cha ra c te riza tio n/ Va lida tio n Wo rking Gro up

7. Binding Wo rking Gro up
8. RNA Wo rking Gro up
9. DNa se Wo rking Gro up

SLIDE 40

Majo r Collabo r ations and T he ir Goals:

1. Co mmo n F

und E pig e no mic s Pro je c t (L e a d I C: NI E HS a nd NI DA)

i. Pro je c t de sc riptio n: https:/ / c o mmo nfund .nih.g o v/ e pig e no mic s/
ii. Da ta po rta l: http:/ / www.ro a dma pe pig e no mic s.o rg /
2. I

nte rna tio na l Huma n E pig e no me Co nso rtium (I HE C): http:/ / www.ihe c -e pig e no me s.o rg /

3. Ge no type -T

issue E xpre ssio n (GT E x): https:/ / c o mmo nfund .nih.g o v/ GT E x/ ind e x

4. E

le c tro nic Me dic a l Re c o rds a nd Ge no mic s (e ME RGE ) Ne two rk: https:/ / e me rg e .mc .va nde rb ilt.e du/

Re so ur c e s and T

o ls Pr
duc e d:
1. E

NCODE Co nso rtium Da ta Po rta l: https:/ / www.e nc o de pro je c t.o rg /

2. E

NCODE tuto ria ls: http:/ / www.g e no me .g o v/ 27553900 F ive Ke y Pub lic atio ns: Se e : https:/ / www.e nc o d e pro je c t.o rg / p ub lic a tio ns fo r links to E NCODE

funde d pub lic a tio ns a nd to c o mmunity

pub lic a tio ns fro m g ro ups no t funde d b y ENCODE, inc luding se ve ra l hundre d huma n dise a se studie s (https:/ / www.e nc o de pro je c t.o rg / se a rc h/ ? type =p ub lic a tio n&pub lishe d_b y=c o mmunity&c a te g o rie s=huma n%20dise a se ).

1. Ma ura no , M.T

., e t a l (2012) Syste ma tic lo c a liza tio n o f c o mmo n dise a se -a sso c ia te d va ria tio n in re g ula to ry DNA. Sc ie nc e 337(6099):1190. do i: 10.1126/ sc ie nc e .1222794

2. Sc ha ub MA, Bo yle AP, K

unda je A, Ba tzo g lo u S, Snyde r M. (2012) L inking dise a se a sso c ia tio ns with re g ula to ry info rma tio n in the huma n g e no me . Ge no me Re s. 22(9):1748. d o i: 10.1101/ g r.136127.111

3. Bo yle , A.P., e t a l (2012) Anno ta tio n o f func tio na l va ria tio n in pe rso na l g e no me s using Re g ulo me DB. Ge no me Re s.

22(9):1790. d o i: 10.1101/ g r.137323.112

4. Wa rd, L

.D., a nd K e llis, M. (2012) Ha plo Re g : a re so urc e fo r e xplo ring c hro ma tin sta te s, c o nse rva tio n, a nd re g ula to ry mo tif a lte ra tio ns within se ts o f g e ne tic a lly linke d va ria nts. Nuc le ic Ac ids Re s. 40(Da ta b a se issue ):D930. do i: 10.1093/ na r/ g kr917

5. T

he E NCODE Pro je c t Co nso rtium (2012) An inte g ra te d e nc yc lo pe dia o f DNA e le me nts in the huma n g e no me . Na ture 489(7414): e 11247. d o i:10.1038/ na ture 11247 Majo r Ob stac le s and Ne e ds that Mig ht b e F ac ilitate d b y Ge no mic Me dic ine Re se arc h:

Ma jor Obsta c le s a nd Ne e ds Approa c he s Conside re d or Propose d to O ve rc ome Obsta c le s

No ne kno wn a t this time

NHG RI Pr

am Offic ials: E

lise F e ing o ld, Da n Gilc hrist, Mike Pa zin

SLIDE 41

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am GA4GH

am Name and We b site : Glo b a l Allia nc e fo r Ge no mic s a nd He a lth, http:/ / g e no mic sa ndhe a lth.o rg / Ste e r ing Co mmitte e Me mbe r s:

Da vid Altshule r Ve rte x Pha rma c e utic a ls Ma rtin Bo b ro w Unive rsity o f Ca mb ridg e K a thryn No rth Murdo c h Childre n’ s Re se a rc h I nstitute Dixie Ba ke r Ma rtin, Bla nc k a nd Asso c ia te s Ric ha rd Durb in We llc o me T rust Sa ng e r I nstitute Pa ul F lic e k E uro pe a n Bio info rma tic s I nstitute Pe te r Go o dha nd Glo b a l Allia nc e fo r Ge no mic s a nd He a lth Da vid Ha ussle r Unive rsity o f Ca lifo rnia , Sa nta Cruz T ho ma s Hudso n Onta rio I nstitute fo r Ca nc e r Re se a rc h K a zuto K a to Osa ka Unive rsity Ba rtha K no ppe rs Ce ntre o f Ge no mic s a nd Po lic y Bra d Ma rg us A-T Childre n’ s Pro je c t E liza b e th Na b e l Brig ha m a nd Wo me n’ s Ho spita l Cha rle s Sa wye rs Me mo ria l Slo a n K e tte ring Ca nc e r Ce nte r

Obje c tive s: T

a c c e le ra te pro g re ss in huma n he a lth b y he lping to e sta b lish a c o mmo n fra me wo rk o f ha rmo nize d

a ppro a c he s to e na b le e ffe c tive a nd re spo nsib le sha ring o f g e no mic a nd c linic a l da ta , a nd b y c a ta lyzing da ta sha ring pro je c ts tha t drive a nd de mo nstra te the va lue o f da ta sha ring .

F unding Pe r iod and FY14 T

tal:

Cur r e nt Intr a-Pr

am Wo r king Gr

ups:

1. Clinic a l Wo rking Gro up 2. Da ta Wo rking Gro up 3. Re g ula to ry a nd E thic s Wo rking Gro up 4. Se c urity Wo rking Gro up

Majo r Collabo r ations and T he ir Goals:

1. BRC A Cha lle ng e : to po o l da ta o n va ria nts fro m c urre nt se q ue nc ing e ffo rts, c o uple d with phe no type da ta , a s a n inte rna tio na l da ta sha ring re so urc e to impro ve id e ntific a tio n o f c linic a lly a c tio na b le va ria nts. 2. Ma tc hma ke r E xc ha ng e : to a llo w re se a rc he rs a nd c linic ia ns wo rking in b o th g e rmline a nd c a nc e r to disc o ve r sa mple s with a g ive n ra re g e no type o r Me mb e r. 3. Be a c o n Pro je c t: to te st the willing ne ss o f inte rna tio na l site s to sha re g e ne tic da ta in the simple st o f a ll te c hnic a l c o nte xts.

Re sour c e s and T

o ls Pr
duc e d (se le c te d, se e http:/ / ge no mic sandhe alth.o r

g/ o ur-wor k/ c ur r e nt-initiative s for mor e c o mple te list):

1. Co nstitutio n o f the Glo b a l Allia nc e fo r Ge no mic s a nd He a lth 2. Ca ta lo g o f Ac tivitie s – e He a lth, Me nde lia n 3. Ge no mic s API 4. Ma tc hma ke r E xc ha ng e API 5. Me ta da ta Spe c ific a tio n 6. Co nse nt Po lic y a nd T

o ls

7. F ra me wo rk fo r Re spo nsib le Sha ring o f Ge no mic a nd He a lth-Re la te d Da ta 8. Po lic y T e mpla te 9. Priva c y a nd Se c urity Po lic y

F ive Ke y Public atio ns:

1. White Pa pe r: Cre a ting a Glo b a l Allia nc e to E na b le Re sp o nsib le Sha ring o f Ge no mic a nd Clinic a l Da ta 2. K no ppe rs BM. F ra me wo rk fo r re spo nsib le sha ring o f g e no mic a nd he a lth-re la te d da ta . T he HUGO Jo urnal 2014, 8:3. http:/ / www.the hug o jo urna l.c o m/ c o nte nt/ 8/ 1/ 3. d o i:10.1186/ s11568-014-0003-1.

SLIDE 42

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am GAPH

am Name and We b site : 2012 L

a rg e -Sc a le Ap plie d Re se a rc h Pro je c t Co mpe titio n in Ge no mic s a nd Pe rso na lize d He a lth (GAPH), http:/ / www.g e no me c a na da .c a / e n/ p o rtfo lio / re se a rc h/ 2012-c o mpe titio n.a spx

je c ts, L

e ad Ce ntr e s, Pro je c t L e ade r (s): Proje c t L e a d Ge nome Ce ntre / Co- L e a d Ce ntre Proje c t L e a de r(s)

Autism Spe c trum Diso rde rs: Ge no me s to Outc o me s Onta rio Ge no mic s I nstitute Sc he re r, Ste phe n Sza tma ri, Pe te r Bio ma rke rs fo r Pe dia tric Glio b la sto ma thro ug h Ge no mic s a nd E pig e no mic s Ge no me Que b e c Ja b a do , Na da Ma je wski, Ja c e k Clinic a l I mple me nta tio n a nd Outc o me s E va lua tio n o f Blo o d-b a se d Bio ma rke rs fo r COPD Ma na g e me nt Ge no me British Co lumb ia Sin, Do n Ng , Ra ymo nd E a rly De te c tio n o f Pa tie nts a t Hig h Risk o f E so pha g e a l Ad e no c a rc ino ma Onta rio Ge no mic s I nstitute Ste in, L inc o ln Go d fre y, T

E nha nc e d CARE fo r RARE Ge ne tic Dise a se s in Ca na da Onta rio Ge no mic s I nstitute Bo yc o tt, K ym Ma c ke nzie , Ale x I BD Ge no mic Me dic ine Co nso rtium (iGe no Me d): T ra nsla ting Ge ne tic Disc o ve rie s into a Pe rso na lize d Appro a c h to T re a ting I nfla mma to ry Bo we l Dise a se s Ge no me Que b e c Rio ux, Jo hn Bitto n, Ala in I nno va tive Che mo g e no mic T

o ls to I

mpro ve Outc o me in Ac ute Mye lo id L e uke mia Ge no me Que b e c Sa uva g e a u, Guy Hé b e rt, Jo sé e PACE

'Omic s: Pe rso na lize d, Ac c e ssib le , Co st-E

ffe c tive Applic a tio ns o f 'Omic s T e c hno lo g ie s Ge no me Alb e rta Mc Ca b e , Christo phe r Bub e la , T a nia PE GASUS: Pe rso na lize d Ge no mic s fo r Pre na ta l Ane uplo id y Sc re e ning Using Ma te rna l Blo o d Ge no me Que b e c , Ge no me

Br. Co lumb ia

Ro usse a u, F ra nc o is L a ng lo is, Sylvie Pe rso na lize d Ca nc e r I mmuno the ra py Ge no me Que b e c Pe rre a ult, Cla ude Ro y, De nis-Cla ude Pe rso na lize d Me dic ine in the T re a tme nt o f E pile psy Ge no me Que b e c Co sse tte , Pa tric k Mina ssia n, Be rg e Mic ha ud, Ja c q ue s Pe rso na lize d Me dic ine Stra te g ie s fo r Mo le c ula r Dia g no stic s a nd T a rg e te d T he ra pe utic s o f CVD Ge no me Que b e c T a rdif, Je a n-Cla ud e Dub é , Ma rie -Pie rre Pe rso na lize d Risk Stra tific a tio n fo r Pre ve ntio n a nd E a rly De te c tio n o f Bre a st Ca nc e r Ge no me Que b e c Sima rd , Ja c q ue s K no ppe rs, Ba rtha Pe rso na lize d T re a tme nt o f L ympho id Ca nc e r: British Co lumb ia a s Mo de l Pro vinc e Ge no me British Co lumb ia Co nno rs, Jo se ph Ma rra , Ma rc o Re d uc ing Stro ke Burde n with Ho spita l-Re a dy Bio ma rke r T e st fo r Ra pid T IA T ria g e Ge no me British Co lumb ia Pe nn, Andre w Bo rc he rs, Christo ph T he Mic ro b io ta a t the I nte stina l Muc o sa -I mmune I nte rfa c e : A Ga te wa y fo r Pe rso na lize d He a lth Onta rio Ge no mic s I nstitute Stintzi, Ala in Ma c k, Da vid Vira l a nd Huma n Ge ne tic Pre dic to rs o f Re sp o nse to HI V T he ra pie s Ge no me British Co lumb ia Ha rrig a n, Ric ha rd Mo nta ne r, Julio

Obje c tive s: T

de mo nstra te ho w g e no mic s-b a se d re se a rc h c a n c o ntrib ute to a mo re e vide nc e -b a se d a ppro a c h to

he a lth a nd impro ving the c o st-e ffe c tive ne ss o f the he a lth-c a re syste m. Sp e c ific a lly: 1. T

de ve lo p a n e vide nc e b a se o n ho w to a sse ss a nd, whe re a ppro pria te , inte g ra te inno va tive dia g no stic s

(inc luding la b o ra to ry dia g no stic s a nd me dic a l ima g ing ) into he a lth po lic y a nd pra c tic e .

SLIDE 43

2. T

stimula te the disc o ve ry, va lida tio n, a nd tra nsla tio n o f b io ma rke rs, ta rg e ts a nd g e no mic sig na ture s fo r risk

pre ve ntio n a nd fo r dise a se s, whic h ha ve the po te ntia l to impro ve the o utc o me s o f the ra pe utic inte rve ntio ns b y se le c ting ta ilo ring o f tre a tme nt c ho ic e s to individua l pa tie nt c ha ra c te ristic s? 3. T

fo ste r the de ve lo pme nt a nd va lida tio n o f dia g no stic s b a se d o n suc h b io ma rke rs, ta rg e ts a nd g e no mic

sig na ture s, a nd o f inno va tive de vic e s fo r the a pplic a tio n to pa tie nt pra c tic e .

F unding Pe r iod and FY14 T

tal: F

Y2013-F Y2016: $149.8M (Ge no me Ca na da , Ca na dia n I nstitute fo r He a lth Re se a rc h, re g io na l g e no me c e ntre s, o the rs), ~$37.5M in F Y14

Cur r e nt Intr a-Pr

am Wo r king Gr

ups: L

e ar ning Ne two r k in the pr

c e ss o f be ing de ve lo pe d and will be funde d by

Ge no me Canada Majo r Co llabor ations and T he ir Goals: Info r matic s Infr astr uc tur e for G e no mic s and He alth (aligne d with the Glo bal Allianc e for G e no mic s and He alth and funde d by Ge nome Canada and CIHR. Re so ur c e s and T

o ls Pr
duc e d: T

BD F ive Ke y Public atio ns: (to be adde d) Majo r Obstac le s o r Ne e ds E nc o unte r e d: Ma jor Obsta c le s or Ne e ds Approa c he s Imple me nte d or Propose d to Ove rc ome Obsta c le s

De ve lo p re c e pto r c a pa c ity fo r te c hno lo g y pull (c a pa c ity fo r c linic a l a nd tra nsla tio na l re se a rc h) E ng a g e with the re g io na l he a lth a utho ritie s a nd pro vinc ia l ministrie s o f he a lth (tho se tha t pa y fo r he a lth c a re de live ry in Ca na da ) to unde rsta nd the ir ne e ds a nd prio ritie s I nvo lve the priva te se c to r Cre a te fo rums whe re ind ustry pla ye rs c a n b e e xp o se d to wha t is ha ppe ning inside the pro je c ts E duc a te a nd tra in he a lthc a re pro fe ssio na ls to b e pro fic ie nt use rs o f the te c hno lo g y CI HR to fund tra ining ne two rks a s pa rt o f the ir Pa tie nt Orie nte d Re se a rc h initia tive E nsure info rma tio n syste ms a re sta te o f the a rt a nd ha rmo nize e -pa tie nt re c o rds E ng a g e with the ma jo r a c to rs in he a lth info rma tic s infra struc ture de ve lo pme nt (in Ca na d a se ve ra l pla ye rs a re invo lve d a nd the sc e ne is fra g me nte d). Alig n Ca na da mo re with the Glo b a l Allia nc e fo r Ge no mic s a nd He a lth (Ge no me Ca na da a nd CI HR to fund spe c ific a c tivitie s to “:g e t o ur a c t to g e the r” I nc re a se the ro le o f pa tie nts a nd a dvo c a c y g ro up s in de ma nding e vide nc e b a se d me dic ine I nvo lve pa tie nts a nd a dvo c a c y g ro up s within o ur pro je c ts (this is no t do ne syste ma tic a lly a s ye t) Apply ro b ust te c hno lo g y a sse ssme nts fo c use d

n impro ve me nt o f c linic a l o utc o me s a nd

e c o no mic b e ne fit a na lyse s Cre a te a le a rning ne two rk a c ro ss the 17 pro je c t in the GAPH po rtfo lio to c re a te ro b ust me tho do lo g ie s fo r HT A tha t de ve lo p c o nc re te “va lue pro po sitio ns”. Ge no me Ca na da will fund suc h a ne two rk tha t is in the pro c e ss o f b e ing put to g e the r

SLIDE 44

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am GGR

am Name and We b site : Ge no mic s o f Ge ne Re g ula tio n (GGR), http:/ / www.g e no me .g o v/ 27561317 PIs and F unde d Site s: Proje c ts (5):

Ale xa nd e r Ho ffma nn, Ph.D. a nd Do ug la s Bla c k, Ph.D. Unive rsity o f Ca lifo rnia , L

s Ang e le s

Christina L e slie , Ph.D. a nd Ale xa nde r Rude nsky, Ph.D. Me mo ria l Slo a n K e tte ring Ca nc e r Ce nte r Je re my L ub a n, M.D. a nd Ma nue l Ga rb e r, Ph.D. Unive rsity o f Ma ssa c huse tts Me dic a l Sc ho o l T imo thy Re ddy, Ph.D. Duke Unive rsity Mic ha e l Snyde r, Ph.D. Sta nfo rd Unive rsity

Da ta Ce nte r, ENCODE DCC:

J. Mic ha e l Che rry

Sta nfo rd Unive rsity

Obje c tive s:

T he g o a l o f the Ge no mic s o f Ge ne Re g ula tio n (GGR) pro je c t is to de ve lo p b e tte r me tho ds to c o nstruc t pre dic tive , a c c ura te g e ne re g ula to ry ne two rk mo de ls using g e no mic da ta . T he a b ility to ma ke a c c ura te pre dic tio ns fro m g e ne re g ula to ry ne two rks c o uld supp o rt g e no mic me dic ine a nd pre c isio n me dic ine , b y pro viding us o ne mo re to o l to unde rsta nd the c o nse q ue nc e s o f g e ne tic va ria tio n.

F unding Pe r iod and FY14 T

tal: F

Y15-17; F Y14 to ta l is $0

Cur r e nt Intr a-Pr

am Wo r king Gr

ups: No ne

Majo r Collabo r ations and T he ir Goals: No c o lla b o ra tio ns a t this time Re so ur c e s and T

o ls Pr
duc e d: No ne a t pre se nt

F ive Ke y Public atio ns: No ne a t pre se nt

Majo r Ob stac le s and Ne e ds that Mig ht b e F ac ilitate d b y Ge no mic Me dic ine Re se arc h:

Ma jor Obsta c le s a nd Ne e ds Approa c he s Conside re d or Propose d to O ve rc ome Obsta c le s

NONE

NHG RI Pr

am Dir e c tor : Mike Pa zin

SLIDE 45

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am GS-IT

Pro g ram Name and We b site : Ge nome Se que nc ing Informa tic s T

ols (GS- IT

)

GS-I T Pro g ra m: http:/ / www.g e no me .g o v/ 27546195 iSe q to o ls Po rta l: http:/ / ise q to o ls.o rg PI s and Funde d Site s: E ric Ba nks Bro a d I nstitute Ste ve Mc Ca rro ll Ha rva rd Me dic a l Sc ho o l Ali T

rka ma ni

T he Sc ripps Re se a rc h I nstitute Ga b o r Ma rth Unive rsity o f Uta h Go nc a lo Ab e c a sis Unive rsity o f Mic hig a n L i Ding Wa shing to n Unive rsity in St. L

T ing Che n, E wa De e lma n Unive rsity o f So uthe rn Ca lifo rnia Ob je c tive s: 1. De ve lo p re se a rc he r frie ndly se q ue nc e a na lysis to o ls a nd so ftwa re fo r a b ro a d c o mmunity o f sc ie ntist who re ly o n g e no mic s 2. Ac c e ss to the se to o ls is d e mo c ra tize d to pro vide e a sy a c c e ss to use ful a na lysis so ftwa re to inde pe nde nt re se a rc he rs 3. I nve st in e xisting to o ls o f kno wn utility to ma ke the m ro b ust, re lia b le , e a sy to use , a nd we ll-suppo rte d fo r e a sy a do ptio n b y re se a rc he rs 4. De ve lo pme nt o f inno va tive stra te g ie s o n the c lo ud to a id re se a rc he rs a c hie ve the ir g o a ls 5. De plo yme nt o f inte ra c tive visua liza tio n me tho ds to furthe r de mo c ra tize a c c e ss to se q ue nc e a na lysis to o ls a nd so ftwa re

F unding Pe r iod and FY14 T

tal: F

Y2012 - F Y2016, $4 M in F Y14

Cur r e nt Intr a-Pr

am Wo r king Gr

ups: Clo ud Wo rking Gro up

Majo r Collabo r ations and T he ir Goals:

Pilo ts with da ta pro duc e rs
Ce nte rs fo r Me nde lia n Ge no mic s – c o mple x inde ls
Undia g no se d Dise a se Pro g ra m – da ta sha ring

Re so ur c e s and T

o ls Pr
duc e d:

Ove rvie w a t iSe q T

o ls Po rta l: http:/ / ise q to o ls.o rg

Mo st re le vant to g e no mic me dic ine : 1. SG-ADVI SE R CNV: c o p y-numb e r va ria nt a nno ta to r/ inte rpre te r: https:/ / g e no mic s.sc ripps.e d u/ ADVI SE R/ 2. Ge no me ST RiP CNV: c o p y-numb e r va ria nt pre dic to r pipe line : http:/ / www.b ro a dinstitute .o rg / so ftwa re / g e no me strip/ 3. I OBI O: we b -b a se d, re a l-time , g e no mic a na lysis (se e vide o : http:/ / io b io .io ) 4. Co mb ine Va ria nts GK NO pipe line : Ac c ura te , g ra p h-b a se d me rg ing a nd e va lua tio n o f va ria nt c a lls: http:/ / g kno .me / 5. L a rg e -sc a le c lo ud-e na b le d se q ue nc e pro c e ssing : GAT K, Go tClo ud , GK NO, Ge no me VI P

F ive Ke y Public atio ns:

1. E

rikso n, G. A., De shpa nd e , N., Ke sa va n, B. G. & T

rka ma ni, A. “ SG-ADVI

SE R CNV: c o py-numb e r va ria nt a nno ta tio n a nd inte rpre ta tio n” Ge ne t. Me d. (2014) [T

rka ma ni]
2. Ha ndsa ke r, R. E. e t al. “L

a rg e multia lle lic c o py numb e r va ria tio ns in huma ns” Nat. Ge ne t. 47, 296–303 (2015) [Mc Ca rro ll]

3. Mille r, C. A., Qia o , Y., DiSe ra , T

., D’ Asto us, B. & Ma rth, G. T . “b a m.io b io : a we b -b a se d, re a l-time , se q ue nc e a lig nme nt file inspe c to r” Nat. Me tho ds 11, 1189 (2014) [Ma rth]

4. Jun, G., Wing , M.K., Ab e c a sis, G.R., K

a ng , H.M. An e ffic ie nt a nd sc a la b le a na lysis fra me wo rk fo r va ria nt e xtra c tio n a nd re fine me nt fro m po pula tio n sc a le DNA se q ue nc e da ta ” Ge no me Re se arc h (2015) d o i: 10.1101/ g r.176552.114 [Ab e c a sis]

5. Va n de r Auwe re G. A. e t al. “F

ro m F a stQ da ta to hig h-c o nfide nc e va ria nt c a lls: T he Ge no me Ana lysis T

o lkit Be st

Pra c tic e s pipe line ” Curre nt Pro to c o ls in Bio info rmatic s (2013) do i: 10.1002/ 0471250953.b i1110s43 [Ba nks]

SLIDE 46

Majo r Obstac le s o r Ne e ds E nc o unte r e d: Ma jor Obsta c le s or Ne e ds Approa c he s Imple me nte d/ Propose d to O ve rc ome Obsta c le s

Cha lle ng e fo r re se a rc he rs to insta ll a nd use g e no me se q ue nc e a na lysis so ftwa re with la rg e -sc a le da ta . T hre e -pro ng e d a ppro a c h to c o mb ine ro b ust so ftwa re e ng ine e ring , g o o d supp o rt o f use rs, a nd inno va tio n using c lo ud a nd a pp fra me wo rks. Diffe re nt to o ls fo r va ria nt c a lling do no t pro duc e the sa me re sults a nd it is ha rd to kno w wha t a re the true SNVs. T he b e st, mo st re lia b le pre dic tio ns fo r a pa rtic ula r g e ne c a n b e se le c te d using lo c a l g ra ph re a lig nme nt (se e GKNO Co mb ine Va ria nts) F inding a nd inte rpre ting CNVs a nd SVs is e ve n mo re c ha lle ng ing tha n SNVs. Po we rful ne w to o ls fo r de te c ting a nd a nno ta ting pa tho g e nic impa c t o f CNVs a nd SVs. Re se a rc he rs o fte n wa nt to fo c us o n a g e ne o r se ts o f g e ne s o f inte re st b ut a re fo rc e d to c o nte nd with ma ssive BAM file s. T he I OBI O a pp fra me wo rk pro vide s ra pid , inte ra c tive visua liza tio ns a nd is e a sy to c re a te ne w lig htwe ig ht, intuitive a pps fo r a na lysis.

NHG RI Pr

am Offic ial: He idi Sofia (PO) a nd Ale x L e e (Ana lyst)

SLIDE 47

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am GT E x

Pro g ram Name and We b site : Ge no type T issue E xpre ssio n Pro je c t (GT E x), https:/ / c o mmo nfund .nih.g o v/ GT E x/ inde x

PIs and F unde d Site s: Biospe c ime n Sourc e Site s

Jo hn L

nsda le a nd Je ffe ry T

ho ma s

Na tiona l Dise a se Re s Inte rc ha ng e

Ha ro ld Ma g a zine a nd Ma rk K a rtub

Sc ie nc e Ca re , Inc .

Ba rb a ra F

ste r

Roswe ll Pa rk Ca nc e r Institute Compre he nsive Biospe c ime n Re sourc e

Sc o tt Je we ll Va n Ande l Re se a rc h I nstitute

Compre he nsive Da ta Re sourc e

Na nc y Ro c he L e ido s Bio me dic a l Re se a rc h, I nc .

L a bora tory, Da ta Ana lysis a nd Coord Ce nte r

K ristin Ardlie a nd Ga d Ge tz Bro a d I nstitute

E nha nc ing GT Ex (RF A- RM- 12- 009)

Jo shua Ake y Unive rsity o f Wa shing to n Andre w F e inb e rg Jo hns Ho pkins Unive rsity Ma no lis K e llis MI T Jin Billy L i Sta nfo rd Unive rsity Bra ndo n Pie rc e T he Unive rsity o f Chic a g o Mic ha e l Snyde r a nd Hua T a ng Sta nfo rd Unive rsity Jo hn Sta ma to ya nno po ulo s Unive rsity o f Wa shing to n Ba rb a ra Stra ng e r T he Unive rsity o f Chic a g o

Sta tistic a l Me th (RF A- RM- 09- 006 & RN- 12- 019)

Jun L iu Ha rva rd Unive rsity Christo phe r Bro wn a nd Ba rb a ra E ng le ha rdt Unive rsity o f Pe nnsylva nia Do na ld Co nra d Wa shing to n Unive rsity Na nc y Co x a nd Da n Nic o la e T he Unive rsity o f Chic a g o E mma no uil De rmitza kis, Ca rlo s Busta ma nte , Ro de ric Guig o , Ma rk Mc Ca rthy Unive rsity o f Ge ne va Chia ra Sa b a tti Sta nfo rd Unive rsity Ma tthe w Ste phe ns T he Unive rsity o f Chic a g o F re d Wrig ht a nd Andre w No b e l No rth Ca ro lina Sta te Unive rsity

Obje c tive s:

1. Pro vide a c o mpre he nsive a tla s o f huma n g e ne e xpre ssio n a nd a list o f c is- a nd tra ns- e QT L s a c ro ss multiple huma n tissue s. 2. E sta b lish a re se a rc he r-a c c e ssib le tissue b a nk fo r future g e no mic studie s a nd a da ta po rta l fo r a c c e ssing summa ry da ta . 3. De ve lo p a sta nda rdize d po st-mo rte m b io spe c ime n c o lle c tio n, sto ra g e , a nd a na lysis pipe line . 4. E xplo re the e ffe c tive ne ss o f the do no r c o nse nt pro c e ss to a ddre ss c o nc e rns a nd e xpe c ta tio ns o f p a rtic ipa nts in the study.

F unding Pe r iod and FY14 T

tal: F

Y10-F Y17, $20 millio n pe r ye a r

Cur r e nt Intr a-Pr

am Wo r king Gr

ups:

1. Ana lysis Wo rking Gro up (AWG) 2. 13 AWG sub g ro ups: e QT L s, Se x Bia s a nd Se x spe c ific ity Ana lyse s, Ra re Re g ula to ry Va ria nts, Ge no type , L OF, tra nsc ripto me , GWAS, F unc tio na l a nd Ne two rk Ana lysis, I mprinting , ASE, Be nc hma rking , RNA e diting , Pa tho g e n.

SLIDE 48

3. E nha nc e d GT E x (e GT E x) WG 4. Princ ipa l I nve stig a to r/ Pro g ra m Offic e r WG 5. Pub lic a tio n WG

Majo r Collabo r ations and T he ir Goals:

nc yc lo pe dia o f DNA E le me nts (E NCODE), https:/ / www.e nc o de pro je c t.o rg / ; c o lle c tio n o f 4 d o no rs using GT E x infra struc ture

Sing le Ce ll Ana lysis Pro g ra m (SC AP), https:/ / c o mmo nfund .nih.g o v/ Sing le c e ll/ inde x; using sing le c e ll a na lysis o n

GT E x b ra in tissue s

Re so ur c e s and T

o ls Pr
duc e d:

1. GT E x Co nso rtium Da ta Po rta l: http:/ / www.g te xpo rta l.o rg / ho me / 2. db Ga P: http:/ / www.nc b i.nlm.nih.g o v/ pro je c ts/ g a p/ c g i-b in/ study.c g i? stud y_id=phs000424.v4.p1

F ive Ke y Public atio ns:

1. T he GT E x Co nso rtium. T he Ge no type -T issue E xpre ssio n (GT E x) pilo t a na lysis: Multitissue g e ne re g ula tio n in huma ns. Sc ie nc e . 8 Ma y 2015: Vo l 348 no . 6235 pp 648-660. DOI : 10.1126/ sc ie nc e . 1262110. 2. Me lé e t a l. T he huma n tra nsc ripto me a c ro ss tissue s a nd individua ls. Sc ie nc e . 8 Ma y 2015: Vo l 348 no . 6235 pp 660-665. DOI : 10.1126/ sc ie nc e .a a a 0355 3. Riva s e t a l. E ffe c t o f pre dic te d pro te in-trunc a ting g e ne tic va ria nts o n the huma n tra nsc ripto me . Sc ie nc e . 8 Ma y 2015: Vo l 348 no . 6235 pp 666-669. DOI : 10.1126/ sc ie nc e .1261877. 4. Ba ra n e t a l. T he la ndsc a pe o f g e no mic imprinting a c ro ss dive rse a d ult huma n tissue s. Ge no me Re se a rc h. 8 Ma y

2015. DOI

: 10.1101/ g r.192278.115 5. Pie rso n e t a l. Sha ring a nd spe c ific ity o f c o -e xpre ssio n ne two rks a c ro ss 35 huma n tissue s. 2015. PL OS Co mp ut Bio l. 11(5):e 1004220.

Majo r Obstac le s and Ne e ds that Might be F ac ilitate d by G e no mic Me dic ine Re se ar c h: Ma jor Obsta c le s a nd Ne e ds Approa c he s Conside re d/ Propose d to O ve rc ome Obsta c le s

Da ta is c o ntro lle d a c c e ss Ab ility to re -c o nta c t ne xt-o f-kin to re q ue st o pe n a c c e ss a utho riza tio n L a c k o f c e ntra lize d iPS c e ll re po sito ry Cha ng e d c o nse nt to a llo w iPS c e ll c re a tio n a nd c o mpa riso n with ma tc hing tissue s Re turn o f inc ide nta l finding s (I F ) a ffe c ting o rg a n re c ipie nts a nd/ o r fa mily me mb e rs Cre a tio n o f a c o mmitte e to e va lua te re turn o f I F to o rg a n re c ipie nts. Guide line s o n re turning g e no mic re sults re le va nt to fa mily me mb e rs.

NHG RI Pr

am Offic ials: Simo na Vo lpi a nd Je ff Strue wing

SLIDE 49

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am H3AF RICA

Pro g ram Name and We b site : Huma n He re dity a nd He a lth in Afric a (H3Afric a ) http:/ / h3a fric a .o rg / PI s and Funde d Site s:

Cle me nt Ade ba mowo Institute of Huma n Virolog y, Abuja , Nig e ria

Dwo mo a Ad u a nd Akinlo lu Ojo Unive rsity o f Gha na Me dic a l Sc ho o l, Ac c ra , Gha na a nd Unive rsity o f Mic hig a n, Ann Arb o r, Mic hig a n, U.S.A. Ga b rie l Ana b wa ni; Mo se s Jo lo b a ; Ade o da ta K e kitiinwa ; Gra e me Ma rdo n; Wa ta Mpo lo ka ; a nd Oa tho kwa Nko ma za na Bo tswa na -Ba ylo r Childre n’ s Clinic a l Ce ntre o f E xc e lle nc e , Ga b o ro ne , Bo tswa na ; Ma ke re re Unive rsity Co lle g e o f He a lth Sc ie nc e s, K a mpa la , Ug a nda ; Ba ylo r Co lle g e o f Me dic ine Childre n’ s Fo unda tio n, Ka mpa la , Ug a nda ; Ba ylo r Co lle g e o f Me dic ine , Ho usto n, T e xa s, U.S.A.; Unive rsity o f Bo tswa na F a c ulty o f Bio lo g ic a l Sc ie nc e s, Ga b o ro ne , Bo tswa na ; a nd Unive rsity o f Bo tswa na F a c ulty o f He a lth Sc ie nc e s, Ga b o ro ne , Bo tswa na Ma yo wa Ojo Owo la b i a nd Bruc e Ovb ia g e le Unive rsity o f I b a da n, I b a da n, Nig e ria a nd Me dic a l Unive rsity

f So uth Ca ro lina , Cha rle sto n, So uth Ca ro lina , U.S.A.

Mic he le Ra msa y a nd Osma n Sa nko h Unive rsity o f Witwa te rsra nd & NHL S, Jo ha nne sb urg , So uth Afric a a nd I nte rna tio na l Ne two rk fo r the De mo g ra phic E va lua tio n o f Po p ula tio ns a nd T he ir He a lth in De ve lo ping Co untrie s (I NDE PT H), Ac c ra , Gha na E no c k Ma to vu Ma ke re re Unive rsity, K a mpa la , Ug a nda Bo ng a ni Ma yo si Unive rsity o f Ca pe T

wn, Ca pe T
wn, So uth Afric a

Aye sha Mo ta la Unive rsity o f K wa Zulu-Na ta l, Durb a n, So uth Afric a

Dissou Affola bi Na tiona l Hospita l for T ube rc ulosis a nd Pulmona ry Dise a se s, Cotonou, Be nin

Go b e na Ame ni Ad dis Ab a b a Unive rsity, Ad dis Ab a b a , E thio pia Christia n Ha ppi Re de e me r’ s Unive rsity, Re de mptio n City, Nig e ria

Guida L a ndoure Unive rsity of Ba ma ko, Ba ma ko, Ma li

Ma rk Nic o l Unive rsity o f Ca pe T

wn, Ca pe T
wn, So uth Afric a

Hug h-Ge o rg e Pa tte rto n Unive rsity o f the F re e Sta te , Blo e mfo nte in, So uth Afric a Da n Ste in a nd Ra j Ra me sa r Unive rsity o f Ca pe T

wn, Ca pe T
wn, So uth Afric a

Amb ro ise Wo nka m Unive rsity o f Ca pe T

wn, Ca pe T
wn, So uth Afric a

Ge tne t T a de le Ad dis Ab a b a Unive rsity, Ad dis Ab a b a , E thio pia Alic e Ma timb a , L

ve mo re Gwa nzura a nd

Rug a re K a ng we nde , Unive rsity o f Zimb a b we Co lle g e o f He a lth Sc ie nc e s, Ha ra re , Zimb a b we a nd Afric a Unive rsity Clinic a l Re se a rc h Ce ntre , Muta re , Zimb a b we K e yma nthri Mo o dle y Ste lle nb o sc h Unive rsity T yg e rb e rg Ca mp us Ja ntina de Vrie s Unive rsity o f Ca pe T

wn, Ca pe T
wn, So uth Afric a

Nic o la Mulde r Unive rsity o f Ca pe T

wn, Ca pe T
wn, So uth Afric a

Ute Je ntsc h Wits He a lth Co nso rtium (Pty) L td, Jo ha nne sb urg , So uth Afric a Ala sh’ le Ab imiku I nstitute o f Huma n Viro lo g y, Ab uja , Nig e ria Mo se s Jo lo b a Ma ke re re Unive rsity Co lle g e o f He a lth Sc ie nc e s, Ka mpa la , Ug a nda

Obje c tive s:

fa c ilita te a c o nte mpo ra ry re se a rc h a ppro a c h to the study o f g e no mic s a nd e nviro nme nta l de te rmina nts o f

c o mmo n dise a se s with the g o a l o f impro ving the he a lth o f Afric a n po pula tio ns. T

a c c o mplish this, the H3Afric a

I nitia tive a ims to c o ntrib ute to the de ve lo pme nt o f the ne c e ssa ry e xpe rtise a mo ng Afric a n sc ie ntists, a nd to e sta b lish ne two rks o f Afric a n inve stig a to rs.

SLIDE 50

F unding Pe rio d and F Y14 T

tal:

F Y12-F Y16 (F Y18 fo r Bio re po sito rie s); $67,737,884 (p lus $15,000,000+ fro m We llc o me T rust) Majo r Co llab o ratio ns and T he ir Go als:

his initia tive is c o lla b o ra tio n b e twe e n NI H Co mmo n F und , We llc o me T rust, a nd the Afric a n So c ie ty o f Huma n Ge ne tic s F ive Ke y Pub lic atio ns: 1. Re se a rc h c a pa c ity. E na b ling the g e no mic re vo lutio n in Afric a . H3Afric a Co nso rtium, Sc ie nc e . 2014 Jun 20;344(6190):1346-8. PMI D: 24948725 2. Ge no mic surve illa nc e e luc ida te s E b o la virus o rig in a nd tra nsmissio n during the 2014 o utb re a k. Gire SK , Go b a A, Ande rse n KG, Se a lfo n RS, Pa rk DJ, K a nne h L , Ja llo h S, Mo mo h M, Fulla h M, Duda s G, Wo hl S, Mo se s L M, Yo zwia k NL , Winnic ki S, Ma tra ng a CB, Ma lb o e uf CM, Qu J, Gla dde n AD, Sc ha ffne r SF , Ya ng X, Jia ng PP, Ne ko ui M, Co lub ri A, Co o mb e r MR, F

nnie M, Mo ig b o i A, Gb a kie M, K

a ma ra F K, T uc ke r V, Ko nuwa E , Sa ffa S, Se llu J, Ja llo h AA, K

vo ma A, Ko ning a J, Musta pha I

, K a rg b o K, F

da y M, Yilla h M, K

a nne h F , Ro b e rt W, Ma ssa lly JL , Cha pma n SB, Bo c hic c hio J, Murphy C, Nusb a um C, Yo ung S, Birre n BW, Gra nt DS, Sc he iffe lin JS, L a nde r E S, Ha p pi C, Ge va o SM, Gnirke A, Ra mb a ut A, Ga rry RF, K ha n SH, Sa b e ti PC. Sc ie nc e . 2014 Se p 12;345(6202):1369-72. PMI D: 25214632 3. A c a ll fo r po lic y a c tio n in sub -Sa ha ra n Afric a to re think dia g no stic s fo r pre g na nc y a ffe c te d b y sic kle c e ll dise a se : d iffe re ntia l vie ws o f me dic a l do c to rs, pa re nts a nd a dult pa tie nts pre dic t va lue c o nflic ts in Ca me ro o n. Wo nka m A, Hurst S. OMI

CS. 2014 Jul;18(7):472-80. PMI

D: 24754796 4. T he H3Afric a po lic y fra me wo rk: ne g o tia ting fa irne ss in g e no mic s. d e Vrie s J, T inda na P, L ittle r K , Ra msa y M, Ro timi C, Ab a yo mi A, Mulde r N, Ma yo si BM. T re nds Ge ne t. 2015 Ma r;31(3):117-9. d o i: 10.1016/ j.tig .2014.11.004. E pub 2015 Ja n 15.PMI D: 25601285 5. A q uic k g uide fo r b uilding a suc c e ssful b io info rma tic s c o mmunity. Budd A, Co rpa s M, Bra za s MD, Fulle r JC, Go e c ks J, Mulde r NJ, Mic ha ut M, Oue lle tte BF , Pa wlik A, Blo mb e rg N. PL

S Co mp ut Bio l. 2015 Fe b

5;11(2):e 1003972. PMI D: 25654371

NHG RI Pr

am Offic ials: Je nnife r T

ro ye r, K e n Wile y, E b o ny Ma dde n, Ma rk Guye r, Je ff Strue wing

SLIDE 51

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am HMORN

Pro g ram Name and We b site : HMO Re se a rc h Ne two rk (Will b e re na me d the He a lth Ca re Syste ms Re se a rc h Ne two rk in Aug ust 2015) http:/ / www.hmo re se a rc hne two rk.o rg / e n/ PI s and Funde d Site s: T he HMORN is c o mpo se d o f he a lth c a re de live ry syste ms tha t a re invo lve d in he a lth se rvic e s re se a rc h. I t is funde d thro ug h c o ntrib utio ns o f me mb e r site s. I t do e s ha ve a ny g ra nt funding a s a n e ntity, in fa c t is no t e ve n inc o rpo ra te d a s a n e ntity. F

r g ra nts a nd c o ntra c ts it func tio ns mo re a s a c le a ring ho use whe re a n HMORN site will ta ke the le a d

a nd invo lve o the r site s b a se d in de sire d e xpe rtise a nd willing ne ss to pa rtic ipa te . Ve ry little (if a ny) o f the re se a rc h po rtfo lio fa c ilita te d b y the HMORN is re le va nt to b a sic sc ie nc e disc o ve ry re se a rc h a nd unde rsta nding . Ho we ve r, se ve ra l me mb e rs a re a lso me mb e rs o f NHGRI funde d ne two rks like e ME RGE , so the re is so me e xpe rie nc e with this fro m so me site s.

Obje c tive s:

1. F

ste ring multidisc iplina ry re se a rc h c o lla b o ra tio n

2. Disse mina ting info rma tio n a b o ut the re se a rc h inte re sts, re so urc e s, a nd c a pa b ilitie s o f o ur site s a nd re se a rc he rs 3. Sha ring me tho do lo g ie s, b e st pra c tic e s, a nd c o nsulta tive e xpe rtise a c ro ss re se a rc h c e nte rs 4. L e ve ra g ing o ur uniq ue a sse ts, e spe c ia lly de fine d p o pula tio ns a nd c o mpre he nsive da ta

F unding Pe r iod and FY14 T

tal: N/ A

Cur r e nt Intr a-Pr

am Wo r king Gr

ups:

At pre se nt o nly the Ge no mic Me dic ine Sc ie ntific I nte re st Gro up is o f spe c ific inte re st to NHGRI a c tivitie s. T he missio n

f the Ge no mic s SI

G is to b ring to g e the r HMORN re se a rc he rs wo rking in g e no mic s to fa c ilita te c o lla b o ra tio n a nd re se a rc h o n the tra nsla tio n o f g e no mic te c hno lo g ie s into c linic a l pra c tic e to impro ve the he a lth o f o ur me mb e rs. Ove r 40 individua ls c urre ntly b e lo ng to the SI G with a lmo st a ll HMORN site s re pre se nte d. Majo r Co llab o ratio ns and T he ir Go als: 1. E le c tro nic Me dic a l Re c o rds a nd Ge no mic s (e ME RGE ) Ne two rk: https:/ / e me rg e .mc .va nde rb ilt.e du/ (4 HMORN me mb e rs pa rtic ipa te in the ne two rk, E sse ntia He a lth, Gro up He a lth Co o pe ra tive , Ma rshfie ld Clinic a nd Ge ising e r He a lth Syste m) 2. T he re a re no o the r c urre ntly funde d e ffo rts in g e no mic s tha t ha ve b e e n b ro ke re d thro ug h the HMORN. 3. Curre ntly e xplo ring c o lla b o ra tio n with the NHGRI g e no mic me dic ine wo rking g ro up .

SLIDE 52

Re so ur c e s and T

o ls Pr
duc e d:

1. T he Virtua l Da ta Wa re ho use (VDW). T he VDW is a se rie s o f da ta se t sta nda rds a nd a uto ma te d pro c e sse s in pla c e a t e a c h o f the HMORN site s. T he VDW a llo ws SAS pro g ra ms writte n a t o ne HMORN Site to b e run a g a inst a ll the

the rs q uic kly, a nd with a minimum o f site -spe c ific c usto miza tio n.

http:/ / www.hmo re se a rc hne two rk.o rg / e n/ Ab o ut/ Da ta / http:/ / www.hmo re se a rc hne two rk.o rg / e n/ T

o ls%20&%20Ma te ria ls/ VDW/ VDWSc ie ntists/ HMORN_VDW-Que stio ns-

a nd-Answe rs.pdf 2. Ce ntra lize d I RB po lic ie s a nd g o ve rna nc e . T he HMORN ha s a n I RB c e ding pro c e ss to supp o rt stre a mline d re vie w. A Sta nda rd Ope ra ting Pro c e dure (SOP) do c ume nts po lic ie s a nd pro c e dure s fo r c e de d I RB re vie w o f re se a rc h b e twe e n HMORN site s. T he SOP c o ve rs da ta -o nly, e pide mio lo g ic , a nd he a lth se rvic e s re se a rc h pe rfo rme d in the HMORN fo r whic h pa rtic ipa nt info rme d c o nse nt a nd HI PAA a utho riza tio n ma y o r ma y no t b e re q uire d. T he HMORN’ s I RB c e ding pro c e ss c a nno t b e use d fo r pro spe c tive b io me dic a l re se a rc h studie s o f huma n pa rtic ipa nts invo lving drug s, de vic e s o r b io lo g ic s. http:/ / www.hmo re se a rc hne two rk.o rg / e n/ T

o ls%20&%20Ma te ria ls/ I

RB/ 3. We a re in the pro c e ss o f de ve lo ping a c a ta lo g ue o f b io spe c ime n re so urc e s, c o nse nts a nd g e no mic re se a rc h pro je c ts a t e a c h o f the HMORN site s. Curre nt e stima te s o f re so urc e s: Ove r 300,000 sa mple s a re c urre ntly a va ila b le a c ro ss the HCSRNHMORN. Pro je c te d e nro llme nt e ffo rts a c ro ss HCSRNHMORN site s o ve r the ne xt 5 ye a rs is a ntic ipa te d to pro vide o ve r 1,000,000 sa mple s c o nne c te d to he a lth-re la te d a nd g e no mic da ta .

F ive Ke y Public atio ns:

1. Ste ine r JF , Pa o lino AR, T ho mpso n E E , L a rso n E

B. Susta ining Re se a rc h Ne two rks: the T

we nty-Ye a r E xpe rie nc e o f the HMO Re se a rc h Ne two rk. E GE MS (Wa sh DC). 2014 Jun 9;2(2):1067. e Co lle c tio n 2014. PMC4371441 2. Pa o lino AR, L a uf SL , Pie p e r L E, Ro we J, Va rg a s I M, Go ff MA, Da le y MF, T uzzio L , Ste ine r JF. Ac c e le ra ting re g ula to ry pro g re ss in multi-institutio na l re se a rc h. EGE MS (Wa sh DC). 2014 Jul 10;2(1):1076. do i: 10.13063/ 2327-9214.1076. e Co lle c tio n 2014. PMC4371517 3. Ro ss T R, Ng D, Bro wn JS, Pa rde e R, Ho rnb ro o k MC, Ha rt G, Ste ine r JF . T he HMO Re se a rc h Ne two rk Virtua l Da ta Wa re ho use : A Pub lic Da ta Mo de l to Suppo rt Co lla b o ra tio n. E GE MS (Wa sh DC). 2014 Ma r 24;2(1):1049. do i: 10.13063/ 2327-9214.1049. e Co lle c tio n 2014. PMC4371424 4. Ho lme s JH, Bro wn J, He nne ssy S, L a ne K, L a ng e r RD, L a za rus R, O'Co nno r PJ, Stro m BL , Pla tt R. De ve lo ping a distrib ute d re se a rc h ne two rk to c o nduc t po pula tio n-b a se d studie s a nd sa fe ty surve illa nc e . AMIA Annu Symp Pro c . 2008 No v 6:973. PMI D: 18999251

Majo r Obstac le s and Ne e ds that Might be F ac ilitate d by G e no mic Me dic ine Re se ar c h:

At pre se nt g e no mic me d ic ine re se a rc h is in the e a rly sta g e s o f e xplo ra tio n b y the HMORN. Our ne xt ste p is to ha ve re pre se nta tive s o f the NHGRI Ge no mic Me dic ine Wo rking Gro up pre se nt to the HMORN Ge no mic SI G to b e g in to de te rmine if the re is va lue in c o lla b o ra tio n. We think the HMORN site s c o uld b e a g o o d te st b e d fo r te sting the g e ne ra liza b ility o f g e no mic me dic ine imple me nta tio n pro je c ts funde d b y NHGRI . Also , sinc e mo st HMORN site s ha ve pa ye rs a s pa rt o f the syste m, this c o uld b e a ve nue to c a rry fo rwa rd so me o f the a c tio n ite ms fro m the GM 3 Pa ye rs me e ting .

SLIDE 53

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am IOM

Pro g ram Name and We b site :

IOM Roundta ble on T ra nsla ting Ge nomic - Ba se d Re se a rc h for He a lth

https:/ / www.io m.e d u/ Ac tivitie s/ Re se a rc h/ Ge no mic Ba se dRe se a rc h.a spx

Ro undtable Me mbe r s:

Ge o ffre y Ginsb urg , Duke Unive rsity, Co -Chair Sha ro n T e rry, Ge ne tic Allia nc e , Co -Chair Ro b e rt B. Da rne ll, T he Ro c ke fe lle r Unive rsity Ga b rie la L a ve zza ri, PhRMA Ma ry V. Re lling , St. Jude Childre n's Re se a rc h Ho sp ita l T ho ma s L e hne r, NI MH Da vid L . Ve e nstra , Unive rsity o f Wa shing to n De b ra L e o na rd , C AP Na o mi Aro nso n, BC BS E liza b e th Ma nsfie ld, F DA E ua n Ang us Ashle y, AHA L a ura K. Nise nb a um, E li L illy a nd Co mpa ny Pa ul R. Billing s, L ife T e c hno lo g ie s Ro b e rt M. Ple ng e , Me rc k Bruc e Blumb e rg , K a ise r Pe rma ne nte Vic to ria M. Pra tt, AMP Philip J. Bro o ks, NC AT S Ro na ld Przyg o dzki, VA Jo hn Ca rulli, Bio g e n I DE C Na de e m Sa rwa r, E isa i, I nc . Ann Ca shio n, NI NR Jo a n A. Sc o tt, HRSA Mic ha e l J. Do ug he rty, ASHG Sa m She ka r, No rthro p Grumma n

W. Gre g o ry F

e e ro , JAMA Mic ha e l S. Wa tso n, ACMG Andre w N. F re e dma n, NCI Da nie l Wa tte ndo rf, USAF Je nnife r L . Ha ll, I SCT R Ca the rine A. Wic klund, NSGC Ric ha rd J. Ho de s, NIA Ro b e rt S. Wildin, NHGRI K a the rine Jo ha nse n T a b e r, AMA Ja ne t K . Willia ms, AAN Muin J. K ho ury, CDC

Obje c tive s:

T he Ro undta b le o n T ra nsla ting Ge no mic -Ba se d Re se a rc h fo r He a lth pro vide s b o th a me c ha nism a nd a ve nue fo r inte re ste d pa rtie s fro m g o ve rnme nt, a c a de mia , industry, a nd o the r sta ke ho lde r g ro ups to e xplo re a nd imple me nt stra te g ie s fo r impro ving he a lth thro ug h the tra nsla tio n o f g e no mic s a nd g e ne tic s re se a rc h finding s into me dic ine , pub lic he a lth, e duc a tio n, a nd po lic y. T he prima ry purpo se o f the Ro undta b le is to fo ste r dia lo g ue a c ro ss se c to rs a nd a mo ng sta ke ho lde rs, a nd to ide ntify, illumina te , a nd de ve lo p po te ntia l so lutio ns fo r c ritic a l sc ie ntific a nd po lic y issue s re la te d to the tra nsla tio n o f g e no mic disc o ve rie s. Sinc e its e sta b lishme nt in 2007, the Ro undta b le ha s

rg a nize d a nd ho ste d 25 me e ting s a nd 21 pub lic wo rksho ps a nd pub lishe d 20 wo rksho p summa ry re po rts. T

hro ug h its me e ting s a nd wo rksho ps, the Ro undta b le ha s pro vide d stra te g ic thinking a ro und so me o f the mo st pa ra mo unt issue s fa c ing the fie ld o f g e no mic s inc luding : re turn o f inc ide nta l re sults fro m g e no me se q ue nc ing ; drive rs fo r syste m- wide a do ptio n o f g e no mic me dic ine pro g ra ms; c ha lle ng e s a nd o ppo rtunitie s fo r inte g ra ting g e no mic info rma tio n in the e le c tro nic me dic a l re c o rd ; e thic a l c o nside ra tio ns in c o nduc ting g e no mic s re se a rc h; da ta sha ring ; the use o f g e no mic se q ue nc ing info rma tio n in he a lth c a re de c isio n ma king ; c urre nt DNA sa mple c o lle c tio n pra c tic e s; g e no mic s a s a n e na b le r o f a ne w drug de ve lo pme nt pipe line pa ra dig m; impro ving g ra dua te e d uc a tio n a nd c o ntinuing he a lth pro fe ssio na l e duc a tio n in g e ne tic s; a nd c re a ting g e no mic s-e na b le d le a rning he a lth c a re syste ms a s a me a ns to drive re se a rc h a nd pa tie nt c a re .

F unding Pe r iod and FY14 T

tal: N/ A

Cur r e nt Wor king Gr

ups:

T he wo rk o f the Imple me nta tion Group se e ks to e na b le the use o f g e no mic info rma tio n fo r the b e ne fit o f individua ls a nd c o mmunitie s fo r we llne ss, he a lth c a re , a nd/ o r re se a rc h. T he Evide nc e for Polic y a nd Pra c tic e Group a ims to e na b le sta ke ho lde r de c isio n ma king b y ide ntifying e vide nc e g a ps, prio ritizing tra nsla tio na l re se a rc h, a nd e xplo ring inno va tive me c ha nisms o f e vide nc e g e ne ra tio n. T he ro le o f the Disc ove ry Group is to fa c ilita te a c tio na b le tra nsla tio n o f g e ne tic kno wle dg e into disc o ve ry o f no ve l a nd ta rg e te d the ra pe utic s.

SLIDE 54

Majo r Collabo r ations and T he ir Goals:

Displa ying a nd Inte g ra ting Ge ne tic Informa tion T hroug h the E HR (DIG IT izE ).

Missio n: T
e na b le the sta nda rdize d re pre se nta tio n o f g e ne tic a nd g e no mic info rma tio n in the e le c tro nic

he a lth re c o rd thro ug h a c o lla b o ra tive , multi-sta ke ho lde r a ppro a c h tha t will e nsure inte ro pe ra b ility a nd usa b ility o f the da ta in the c linic a nd fo r re se a rc h a pplic a tio ns.

https:/ / www.io m.e d u/ DI

GI T I ZE 2.

Globa l Ge nomic Me dic ine Colla bora tive (G 2MC).

Missio n: T
ide ntify o ppo rtunitie s a nd fo ste r g lo b a l c o lla b o ra tio ns fo r e na b ling the de mo nstra tio n o f va lue

a nd the e ffe c tive use o f g e no mic s in me dic ine .

https:/ / www.io m.e d u/ G2MC

Se le c te d L ist o f Re sour c e s and T

ols Pr
duc e d:

1. DI GI T izE

minimum list o f da ta e le me nts fo r so ma tic a nd g e rmline g e ne tic te st re po rts, mo de l fo r da ta flo w a c ro ss

the E HR info rma tio n e c o syste m, pro vide r a nd E HR ve ndo r imple me nta tio n g uide s fo r pha rma c o g e no mic use c a se s, a nd fo rma tio n o f pilo t pro je c t pa rtne r units fo r pha se I

f use c a se imple me nta tio n.

2. Ro undtab le Disc ussio n Pape r Se rie s: Analytic Validity o f Ge no mic T e sting , Variant Validity (Se le c te d vs. Ge ne ral Po pulatio n); Clinic al Utility: I nfo rming T re atme nt De c isio ns b y Chang ing the Paradig m; E valuating the Clinic al Utility o f Ge no mic Variants De rive d fro m Ne xt-Ge ne ratio n Se q ue nc ing fo r Oppo rtunistic Dise ase Sc re e ning and Risk Asse ssme nt: E vide nc e Gaps and Prio ritie s; T he Co st-E ffe c tive ne ss o f Clinic al Se q ue nc ing , Re turn o f Antic ipate d and I nc ide ntal Re sults fro m Ne xt-Ge ne ratio n Se q ue nc ing : I mplic atio ns fo r Pro vide rs and Patie nts; Re turn o f Antic ipate d and I nc ide ntal Re sults fro m Ne xt-Ge ne ratio n Se q ue nc ing : I mplic atio ns fo r Pro vide rs and Patie nts; and I mple me ntatio n o f Pharmac o g e no mic s: E vide nc e Ne e ds.

F ive Ke y Public atio ns:

1. Ge no mic s-E nab le d L e arning He alth Care Syste ms: Gathe ring and Using Ge no mic I nfo rmatio n to I mpro ve Patie nt Care and Re se arc h (2015) 2. Asse ssing Ge no mic Se q ue nc ing I nfo rmatio n fo r He alth Care De c isio n Making (2014) 3. I mpro ving the E ffic ie nc y and E ffe c tive ne ss o f Ge no mic Sc ie nc e T ranslatio n (2014) 4. I nte g rating L arg e -Sc ale Ge no mic I nfo rmatio n into Clinic al Prac tic e (2011) 5. Ge ne rating E vide nc e fo r Ge no mic Diag no stic T e st De ve lo pme nt (2011) 6. (F

r a c o mple te list, se e : https:/

/www.io m.e du/Re po rts.aspx? Ac tivity={E 731F 2C3-E 58F

4524-99DC-

AFAF 029998BD})

Majo r Obstac le s and Ne e ds that Might be F ac ilitate d by G e no mic Me dic ine Re se ar c h:

Ma jo r o b sta c le s e xist to imple me nting g e no mic me dic ine , inc luding the e xiste nc e o f sig nific a nt g a ps in the e vide nc e b a se tha t inhib it sta ke ho lde r de c isio n-ma king a nd a n a b se nc e o f g e no mic da ta sta nda rds to re pre se nt g e ne tic info rma tio n within the E

HR. T

he Ro undta b le wo rking g ro ups a nd Ac tio n Co lla b o ra tive s a re fo c using the ir e ffo rts o n a ddre ssing the se a nd o the r issue s to pro vide insig ht o n po ssib le so lutio ns to o ve rc o me the m.

IOM Pr

am Staff: Ada m Be rg e r, Sa ra h Be a c hy, a nd Me re dith Ha c kma nn

SLIDE 55

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am ISCC

Bo b Wildin, MD; GHB Chie f, DPCE , NHGRI ; NI H Co -c hair o f I SCC

Ove rvie w of the ISCC

T he purp o se o f the I nte r-So c ie ty Co o rdina ting Co mmitte e fo r Pra c titio ne r E duc a tio n in Ge no mic s (I SCC, http:/ / www.g e no me .g o v/ 27554614) is to fa c ilita te inte ra c tio ns a mo ng pro fe ssio na l so c ie tie s tha t will e nha nc e the ir e ffo rts to inc re a se the unde rsta nding a nd e xpe rtise o f pra c titio ne rs in a pplying g e no mic re sults to c linic a l c a re . T he c o mmitte e is c ha rg e d with impro ving g e no mic lite ra c y o f physic ia ns a nd o the r pra c titio ne rs a nd e nha nc ing the pra c tic e o f g e no mic me dic ine (tha t is, using a n individua l pa tie nt’ s g e no mic re sults in the ir c linic a l c a re ) thro ug h sha ring o f e d uc a tio na l a ppro a c he s a nd jo int ide ntific a tio n o f e duc a tio na l ne e ds. I n its sta rt-up pha se , the I SCC fo c use d prima rily o n physic ia ns a nd de ntists. T he me mb e rship ha s sinc e e xpa nde d to inc lude nurse s, pha rma c ists, a nd g e ne tic c o unse lo rs. T he c o mmitte e is o pe n to e xpa nding its me mb e rship to inc lude mo re a llie d he a lth pra c titio ne r g ro ups, suc h a s nurse pra c titio ne rs a nd physic ia n a ssista nts. T he I SCC is c urre ntly sup po rte d b y NHGRI sta ff a nd vo lunte e rs. Appro a c he s to susta ina b ility a re unde r e va lua tio n. T he I SCC is le d b y a te a m o f two he a lthc a re pro fe ssio na l c o -c ha irs, o ne fro m NHGRI a nd the o the r fro m a mo ng the me mb e r o rg a niza tio ns. Curre nt Co -Cha irs: Bo b Wildin, MD (Ja nua ry 2015 – pre se nt) Chie f, Ge no mic He a lthc a re Bra nc h, Divisio n o f Po lic y, Co mmunic a tio ns, a nd E duc a tio n, Na tio na l Huma n Ge no me Re se a rc h I nstitute Ann K a rty, MD Me dic a l Dire c to r fo r Co ntinuing Me dic a l E duc a tio n, Ame ric a n Ac a de my o f F a mily Physic ia ns

E volution of the ISCC a nd Produc ts

T he I SCC wa s fo rme d in Fe b rua ry 2013 in re sp o nse to a re c o mme nda tio n fro m the NHGRI Ge no mic Me dic ine Wo rking Gro up (http:/ / www.g e no me .g o v/ 27549220). T he c o mmitte e b e g a n a s the I nte r-So c ie ty Co o rdina ting Co mmitte e fo r Physic ian E duc a tio n in Ge no mic s. T he c o mmitte e ’ s me mb e rship ha s e xpa nde d to inc lude pro fe ssio na l so c ie tie s fo r de ntists, nurse s, pha rma c ists, a nd g e ne tic c o unse lo rs a nd thus b e c a me the I nte r-So c ie ty Co o rdina ting Co mmitte e fo r Prac titio ne r E duc a tio n in Ge no mic s. I SCC le a de rship a nd me mb e rs va lue the disse mina tio n o f fo unda tio na l kno wle dg e , re so urc e info rma tio n, a nd wo rk pro duc ts de ve lo pe d b y I SCC wo rking g ro ups. T he c o mmitte e ha s pub lishe d the fo llo wing two jo urna l a rtic le s in Ge ne tic s in Me dic ine (impa c t fa c to r = 6.435). I SCC wo rking g ro ups a re e nc o ura g e d to c re a te ma nusc ripts hig hlig hting the ir a c hie ve me nts. 1. K

rf, B. e t a l. (2014). F

ra me wo rk fo r de ve lo pme nt o f physic ia n c o mpe te nc ie s in g e no mic me dic ine : re po rt o f the Co mp e te nc ie s Wo rking Gro up o f the I nte r-So c ie ty Co o rdina ting Co mmitte e fo r Physic ia n E duc a tio n in Ge no mic s. Ge ne tic s in Me dic ine , 16(11): 804-809. 2. Ma no lio , T ., Murra y, M., fo r the I nte r-So c ie ty Co o rdina ting Co mmitte e fo r Pra c titio ne r E duc a tio n in Ge no mic s. (2014). T he g ro wing ro le o f pro fe ssio na l so c ie tie s in e duc a ting c linic ia ns in g e no mic s. Ge ne tic s in Me dic ine , 16(8): 571-572.

Me e ting s

Me e ting s a re he ld a ppro xima te ly se mi-a nnua lly. T he I SCC ha s he ld fo ur in-pe rso n me e ting s a nd pla nning is unde rwa y fo r the Ja nua ry 14, 2016 e ve nt. T he me e ting s pro vide a n o ppo rtunity fo r me mb e rs to e xc ha ng e info rma tio n, ha ve g ro up disc ussio ns, fo rmula te o ppo rtunitie s fo r wo rkg ro up fo c us, he a r a b o ut inno va tio ns in pro vide r e duc a tio n, a nd ne two rk. Minute s a nd ma te ria ls fro m e a c h in-pe rso n me e ting a re po ste d o n the we b site . T he re a re a lso mo nthly c o nfe re nc e c a lls fo r ne two rking a nd pro g re ss upda te s.

Working Groups

T he I SCC initia l fo ur c o mmissio ne d wo rking g ro up s ha s g ro wn to se ve n. E a c h wo rking g ro up pla ys a ke y ro le in e ng a g ing me dic a l pro fe ssio na l so c ie tie s, c o lle c ting a nd re vie wing e xisting spe c ia lty-spe c ific e duc a tio na l pro duc ts

SLIDE 56

a nd c o mpe te nc ie s, a nd pro po sing stra te g ie s fo r e sta b lishing c ro ss-spe c ia lty sta nda rds fo r re side nt tra ining a nd pra c tic ing physic ia n e duc a tio n pro g ra ms in g e no mic -b a se d me dic ine .

Working Group De sc ription a nd Ac tivitie s Ca se Studie s

Chairs: Re e d Pye ritz, We ndy Rub inste in Pro d uc e d two hig hly struc ture d, pe e r-re vie we d c a se s a s we ll a s a Ca se Study te mpla te de sig ne d to g uide de ve lo pme nt o f ne w instruc tive c a se s: Mito c ho ndria l DNA Muta tio n A1555G a nd Amino g lyc o side -induc e d He a ring L

ss, a nd Utilizing F

a mily Histo ry to I de ntify L ync h Syndro me . T he c a se s a nd te mpla te a re po ste d o n the I SCC we b site .

Compe te nc ie s (work c omple te d)

Pub lishe d five E PAs tha t c o mprise a b a sic se t o f g e no mic skills: F a mily Histo ry; Ge no mic T e sting ; T re a tme nt Ba se d o n Ge no mic Re sults; So ma tic Ge no mic s; a nd Mic ro b ia l Ge no mic I nfo rma tio n. E PAs a re “e ntrusta b le pro fe ssio na l a c tivitie s” de fine d b y me d ic a l e duc a to rs a s “… tho se pro fe ssio na l a c tivitie s tha t to g e the r c o nstitute the ma ss o f c ritic a l e le me nts tha t

pe ra tio na lly de fine a pro fe ssio n.”

E duc a tion for Insure r Sta ff

Chair: Suzanne Be linso n, Bo b Wildin E xplo re s the g e no mic s e duc a tio na l ne e ds o f sta ff tha t pro c e ss pro vide rs’ a utho riza tio n re q ue sts fo r g e ne tic a nd g e no mic te sting with insura nc e c o mpa nie s. Pla ns a pilo t e duc a tio na l we b ina r se rie s to pro vide sta ff with kno wle dg e fo r e ffic ie nt thro ug hput a nd re so urc e ma na g e me nt, fo llo we d b y e xpa nsio n to se ve ra l o f the la rg e st insure rs.

E duc a tiona l Produc ts

Chair: Kristin We itze l, Je an Je nkins Me mb e rs ide ntify a nd pe e r-re vie w sub mitte d g e no mic e duc a tio n re so urc e s a nd ma p the m to pro vide r c o mpe te nc ie s. T he y a re the n disse mina te d thro ug h the Ge ne tic s a nd Ge no mic s Co mp e te nc y Ce nte r we b site (G2C2, http:/ / g -2-c -2.o rg / ), sta rte d in 2004 a nd ho using >900 e duc a tio na l re so urc e s. T he G2C2 Physic ia n’ s po rta l, with 77 re so urc e s, wa s la unc he d June 2014.

Spe c ia lty Boa rds

Chair: Miriam Blitze r, Je an Je nkins E va lua te a nd e nc o ura g e sha ring inte ra c tio n b e twe e n Spe c ia lty So c ie tie s a nd Spe c ia lty Bo a rds to inc re a se re pre se nta tio n o f g e no mic -me dic ine e va lua tio n in spe c ia lty b o a rd e xa ms a nd ma inte na nc e o f c e rtific a tio n a c tivitie s.

Innova tive Approa c he s to E duc a tion

Chair: Ric hard Haspe l, T e ri Mano lio E xplo re wa ys to furthe r inno va tive pro vide r e d uc a tio na l pro g ra ms, suc h a s flippe d c la ssro o m, de ve lo pe d b y a c urre nt I SCC me mb e r to b e re plic a te d with o the r I SCC me mb e rs’ spe c ia ltie s a nd pro vide r g ro ups. E xe mpla r: http:/ / www.pa tho lo g yle a rning .o rg / trig / re so urc e s.

L a ng ua g e of Ge nomic s

Chair: Suzanne Be linso n, Carla E aste r I nflue nc e pro vide r-pa tie nt c o mmunic a tio ns b y studying the la rg e ly sc ie ntific struc ture o f g e no mic s la ng ua g e a nd o ffe ring a lte rna tive c o nstruc tio ns a nd ima g e ry tha t is c o mmo nly c o nsuma b le b y pa tie nts. T his g ro up invo lve s the industry pa rtne r Blue Cro ss Blue Shie ld Asso c ia tio n.

SLIDE 57

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am L SAC

Pro g ram Name and We b site : T he L a rg e -Sc a le Ge no me Se q ue nc ing a nd Ana lysis Ce nte rs (L SAC) pro g ra m is o ne o f fo ur c o mp o ne nts o f the la rg e r NHGRI Ge no me Se q ue nc ing Pro g ra m (http:/ / www.g e no me .g o v/ 10001691), whic h a lso inc lude s the Ce nte rs fo r Me nde lia n Ge no mic s (CMG), the Clinic a l Se q ue nc ing E xplo ra tio n Ce nte rs (CSE R), a nd the Ge no me Se q ue nc ing I nfo rma tic s T

o ls (GS-I

T ) pro g ra m. PI s and Funde d Site s:

L SAC:

Ric ha rd Gib b s/ E ric Bo e rwinkle Ba ylo r Co lle g e o f Me dic ine E ric L a nde r/ Sta c e y Ga b rie l Bro a d I nstitute o f MI T a nd Ha rva rd Ric ha rd Wilso n Wa shing to n Unive rsity, St. L

Obje c tive s:

1. All fo ur GSP e le me nts we re initia te d to g e the r, b a se d o n sc ie ntific c o nside ra tio ns tha t we re e vide nt fo ur o r five ye a rs a g o , with the stra te g ic inte nt to c o ve r multiple a re a s re la te d to disc o ve ry, c o mmunity use , a nd c linic a l use

f se q ue nc e da ta .

2. T he sc o pe a nd p urpo se o f the L SAC c o mp o ne nt is to pro vide la rg e -sc a le g e no me se q ue nc e da ta se ts a nd a na lyse s in pursuit o f multiple lo ng -te rm g o a ls o f hig h sig nific a nc e to a b ro a d ra ng e o f the b io me dic a l re se a rc h c o mmunity. T he se inc lud e :

ide ntifying so ma tic muta tio ns a sso c ia te d with c a nc e r
c ha ra c te rizing va ria tio n unde rlying c o mple x dise a se ,
pursuing q ue stio ns a b o ut b a sic g e no mic va ria tio n a nd ho w it re la te s to b io lo g y a nd dise a se
e xplo ring b a sic q ue stio ns in c o mpa ra tive a nd e vo lutio na ry g e no mic s thro ug h se q ue nc ing ma ny o rg a nisma l

g e no me s

a dding va lue to mo de l o rg a nism re se a rc h b y pro viding re fe re nc e g e no me se q ue nc e s,

T he se “disc o ve ry” pro je c ts a re c a rrie d o ut in c o lla b o ra tio n with inde pe nde nt study inve stig a to rs a nd thro ug h c o lla b o ra tio ns with o the r I C’ s o n multiple c o nc urre nt pro je c ts (se e b e lo w); pa rt o f the purpo se o f the L SAC pro g ra m is to ide ntify a nd fo ste r the se c o lla b o ra tio ns to wa rds the g e ne ra l sc ie ntific pro g ra m g o a ls. 3. An a dditio na l ke y L SAC g o a l is to a dva nc e the sta te o f the a rt in g e no mic se q ue nc ing thro ug h te c hno lo g ic a l a nd me tho do lo g ic a l impro ve me nts, inc luding impro ve me nts in a na lysis a nd pro je c t de sig n; c o st a nd q ua lity impro ve me nts; de ve lo ping no ve l a pplic a tio ns, e tc .

F unding Pe r iod and FY14 T

tal:
F

Y2011-2015; F Y14 to ta l $77M (L SAC), no t inc luding supple me nts fro m c o lla b o ra ting I C’ s. T he e ntire GSP will b e re struc ture d in 2016 (se e GSP we b site fo r ne w so lic ita tio ns).

Cur r e nt Intr a-Pr

am Wo r king Gr

ups:
All a c tive wo rking g ro ups a re in the c o nte xt o f the L

SAC Pro je c ts (se e b e lo w); L SAC me mb e rs a lso pa rtic ipa te in so me intra -GSP wo rking g ro up s

Majo r Collabo r ations and T he ir Goals:

Be lo w are liste d se ve ral pro mine nt, larg e c o llab o rative pro je c ts unde rtake n b y the L

SAC. All are c o llab o ratio ns to

whic h the L SAC c o ntrib ute s g e no me se q ue nc ing c apac ity and pro je c t de sig n and analysis e xpe rtise . A de taile d list

f all pro je c ts (inc luding sub -pro je c ts)—b o th c o llab o rative and no t--- c an b e fo und at

http:/ /www.g e no me .g o v/ 27557963 1. T he Ca nc e r Ge no me Atla s (with NCI ); L SAC wa s the prima ry pro vide r o f d a ta fo r T CG A, a nd pa rtne rs fo r stud y de sig n a nd a na lysis. (http:/ / c a nc e rg e no me .nih.g o v/ ) 2. T he 1000 Ge no me s Pro je c t (with multiple inte rna tio na l c o lla b o ra to rs; http:/ / www.1000g e no me s.o rg / ) 3. T he Alzhe ime r’ s Dise a se Se q ue nc ing Pro je c t (ADSP; with NI A) https:/ / www.nia g a ds.o rg / a dsp/ c o nte nt/ ho me 4. T he Autism Se q ue nc ing Co nso rtium (ASC; with NI MH); http:/ / www.nc b i.nlm.nih.g o v/ pro je c ts/ g a p / c g i- b in/ study.c g i? stud y_id=p hs000298.v2.p2 5. T he T 2D-Ge ne s Co nso rtium (with NI DDK ; http:/ / t2d -g e ne s.sph.umic h.e d u/ )

SLIDE 58

6. T he T OP-Me d c o nso rtium (dire c t c o -funding fro m NHL BI ; https:/ / www.nhlb iwg s.o rg / ) 7. T he Ge no me Re fe re nc e Co nso rtium http:/ / www.nc b i.nlm.nih.g o v/ pro je c ts/ g e no me / a sse mb ly/ g rc / Re so urc e s and T

o ls Pro duc e d:
Se e Pro je c ts a nd de ta ile d Pro je c t list; da ta se ts (fo r c a se / c o ntro l; re fe re nc e s, e tc .) a re a va ila b le

F ive Ke y Public atio ns:

1. T he E NCODE Pro je c t Co nso rtium (2012) An inte g ra te d e nc yc lo pe dia o f DNA e le me nts in the huma n g e no me . Na ture 489(7414): e 11247. d o i:10.1038/ na ture 11247 2. T he E NCODE Pro je c t Co nso rtium (2011) A Use r's Guide to the E nc yc lo pe dia o f DNA E le me nts (ENCODE ). PL

Bio l 9(4): e 1001046. do i:10.1371/ jo urna l.pb io .1001046 3. E NCODE Pro je c t Co nso rtium, e t al (2007) I de ntific a tio n a nd a na lysis o f func tio na l e le me nts in 1% o f the huma n g e no me b y the E NCODE pilo t pro je c t. Na ture Jun 14;447(7146):799-816. d o i:10.1038/ na ture 0587 4. T he E NCODE Pro je c t Co nso rtium (2004) the E NCODE (E NCyc lo pe dia Of DNA E le me nts) Pro je c t. Sc ie nc e Oc t 22; 306:636-640).

Majo r Obstac le s and Ne e ds that Might be F ac ilitate d by G e no mic Me dic ine Re se ar c h: Ma jor Obsta c le s a nd Ne e ds Approa c he s Conside re d or Propose d to O ve rc ome Obsta c le s

Dra wing to o b rig ht a line b e twe e n disc o ve ry a nd c linic a l e ffo rts is like ly to miss sig nific a nt o ppo rtunitie s in b o th a re a s. Building dire c t c o ntinuity o r c o lla b o ra tio n b e twe e n c linic a l a nd disc o ve ry e ffo rts; ro uting c linic a l pa rtic ipa nts into disc o ve ry re se a rc h pro g ra ms (inc luding b ro a d c o nse nt fo r g e ne ra l re se a rc h use ); impro ve d c linic a l phe no typing da ta fo r use in disc o ve ry pro je c ts; impro ve d da ta re po sito rie s/ re c o rds/ info rma tic s to o ls/ e tc . to e nc o ura g e re a d y upta ke a nd use o f c linic a l da ta in re se a rc h disc o ve ry e ffo rts, a nd c o nve rse ly ra pid upta ke o f va ria nt disc o ve ry re sults b y c linic a l da ta re so urc e s; ma ny o f the se a re fe a ture s o f so me pro po sa ls fo r “ Pre c isio n Me dic ine ”.

NHG RI Pr

am Offic ials: Ad a m F

e lse nfe ld (L SAC); L u Wa ng (CMG); Ca ro lyn Hutte r (T CG A a nd CSE R); L uc ia Hindo rff (CSE R); He idi So fia (GS-I T ).

SLIDE 59

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am MVP

Pro g ram Name and We b site : Millio n Ve te ra n Pro g ra m (MVP) - http:/ /www.re se a rc h.va.g o v/ mvp/

PIs and F unde d Site s:

VA Ce ntra l Offic e T imo thy O’ L e a ry, M.D., Ph.D.; Sumitra Mura lidha r, Ph.D.; Ro na ld Przyg o d zki, Ph.D.; Gra nt Hua ng , Ph.D., M.P.H.; Ja me s Bre e ling , M.D.; Je nnife r Mo se r, Ph.D., K e ndra Sc ha a , K ristina Hill MVP Ste e ring Co mmitte e a nd Sub c o mmitte e s

Ste e r ing Co mmitte e : Jo hn Co nc a to , M.D., M.S., M.P.H., Co -Cha ir; J. Mic ha e l Ga zia no , M.D., M.P.H., Co -Cha ir; Ra ya n

Al Jurdi, M.D.; Ja me s L . Bre e ling , M.D.; L

uis F

io re , M.D., M.P.H., e x-o ffic io ; Jo hn B. Ha rle y, M.D., Ph.D.; E liza b e th Ha use r, Ph.D.; Gra nt Hua ng , M.P.H., Ph.D. E x-Offic io ; Phil T sa o , Ph.D.; Ja ne t D. Cro w, ORD L ia iso n; Philip D. Ha rve y, Ph.D.; T imo thy J. O’ L e a ry, M.D., Ph.D., E x-Offic io ; Ste phe n G. Wa xma n, M.D., Ph.D.; Pe te r W. F. Wilso n, M.D.

Ac c e ss Po lic y Subc o mmitte e : Jo hn, Co nc a to , M.D., M.S., M.P.H., (Cha ir); Sumitra Mura lidha r, Ph.D. (VACO L

ia iso n); Mic ha e l Ha rt, M.D.; Fre d Wrig ht, M.D.; Jo hn (T

m) Ca lla g ha n M.D., Ph.D.; J. Mic ha e l Ga zia no , M.D., M.P.H.; Sa iju

Pya ra ja n, Ph.D. ; Ca rl Grunfe ld, M.D., Ph.D.

Che mic al Analysis Sub c ommitte e : Philip T

sa o , Ph.D. (Cha ir); Ste ve n Sc hic hma n, M.D., Ph.D.; Sa iju Pya ra ja n, Ph.D.; Chris Co rle ss, M.D., Ph.D.; Ro b e rt L undste n; Je nny Mo se r, Ph.D.; Sunil Ahuja , M.D.

Re c r uitme nt Subc o mmitte e : Ra ya n Al Jurdi, M.D. (Cha ir); Je nnife r De e n, He rme s F

lo re z, M.D., Ph.D., M.P.H.; Amy K ilb o urne , Ph.D., M.P.H.; Fra nk L e de rle , M.D.; K e ndra Sc ha a , Sc M, C.G.C. (ORD L ia iso n); Ra lph He ussne r; Ste phe n He rring .

Phe no typing and E pide miology Subc o mmitte e : J. Mic ha e l Ga zia no , M.D., M.P.H. (Cha ir); Je nny Mo se r, Ph.D.; Se th

E ise n, M.D., M.Sc .; Da vid Ga g no n, M.D., Ph.D.; Sa iju Pya ra ja n, Ph.D.; Jo na tha n Ne b e ke r, M.D., M.S.; De nise Hyne s, Ph.D., M.P.H., R.N.; Ma tthe w Sa mo re , M.D. Bo sto n Co o rdina ting Ce nte r (MAVE RI C)

J. Mic ha e l Ga zia no , M.D., M.P.H.; Sta c e y Whitb o urne , Ph.D., Je nnife r De e n; Co lle e n Sha nno n, M.P.H.; K

e lly Cho , Ph.D.; Xua n-Ma i Ng uye n, Ph.D.; Da vid Ga g no n, M.D., Ph.D.; Do na ld Pra tt; L indsa y Ha nse n, M.P.A.; K e ri Ha nna g a n, M.P.H.; De rric k Mo rin We st Ha ve n Co o rdina ting Ce nte r (CE RC) Jo hn Co nc a to , M.D., M.P.H.; Miha e la Asla n, Ph.D.; Pe te r Gua rino , Ph.D.; Da nie l Ande rso n; Re ne L a F le ur; L e sle y Ma nc ini, M.B.A.; Jo hn Russo ; Cindy Cushing ; Va le s Je a n-Pa ul; F re d Sa ywa rd ; L

uis Pisc ite lli; Do nna Ca va lie re

VA Ce ntra l Bio re po sito ry - Bo sto n Ma ry Bro phy, M.D., M.P.H.; Do na ld Humphrie s, Ph.D.; Ge e tha Sug uma ra n, Ph.D.; De b o ra h Go va n; Christine Go va n Ge no mic I nfo rma tio n Syste m fo r I nte g ra te d Sc ie nc e s (Ge nI SI S) - Bo sto n L

uis F

io re , M.D., M.P.H.; Sa iju Pya ra ja n, Ph.D.; T

ny Che n, Ph.D.; E

dmund Pe irc e ; Pa ul Hse ih, Ph.D.; L uis Se lva , Ph.D.; Be th K a tc he r; Ro b e rt Ha ll, M.P.H.; We ijia Mo ; F e lic ia F itzme ye r; Ana hit Ale ksa nya n MVP I nfo rma tio n Ce nte r – Ca na nda ig ua , NY Annie Co rre a ; Me lissa Juhl; Ge o rg e Ba rza c I I I ; L ia m Ce rve ne y; Anne Va n Pa tte n; Jo na tha n Ma rtine z; E ile e n L

ntie r; Je ssic a Ma rino

MVP L

c a l Site I

nve stig a to rs VA HEAL T HC ARE SYST E M UPST AT E NE W YORK: L a ure nc e K a minsky, Ph.D. NEW ME XI CO VA HEAL T HCARE SYST E M: Jo se Ca nive , M.D. AT L ANT A VA ME DI CAL CE NT ER: F a ro o q Amin, M.D. VA MARYL AND HEAL T H C ARE SYST E M: Ala n Shuldine r, M.D.; Miria m Smyth, Ph.D. BAY PI NE S VA HEAL T HCARE SYST E M: Ra c he l Mc a rdle , Ph.D.; T he o do re Stric kla nd, M.D., M.P.H., F.C.A.P. E DI T H NOURSE ROGE RS ME MORIAL VE T E RANS HOSPI T AL : Jo hn We lls, Ph.D. BI RMI NGHAM VA ME DI CAL CE NT E R: L

uis De ll'I

ta lia , M.D.; Ja svinde r Sing h, M.D., M.P.H. VA BOST ON HEAL T HC ARE SYST EM: I ldiko Ha la sz, M.D. VA WE ST E RN NE W YORK HEAL T HC ARE SYST EM: Junzhe Xu, M.D.; Ali A. E l So lh, M.D., M.P.H. CE NT RAL T E XAS VE T E RANS HEAL T H CARE SYST E M: Ke ith Yo ung , Ph.D. RAL PH H. JOHNSON VA ME DI CAL CE NT ER: Ma rk Ha mne r, M.D. CI NCI NNAT I VA ME DI CAL CE NT E R: Jo hn B. Ha rle y, M.D., Ph.D. L OUI S ST OK E S CL E VE L AND VA ME DI CAL CENT E R: E ric K

nic ki, M.D.; Curtis Do nske y, M.D. WM. JE

NNI NGS BRYAN DORN VA ME DI CAL CE NT E R: K a thlyn Sue Ha ddo c k, R.N., Ph.D. VA NORT H T E XAS HEAL T H C ARE SYST E M: Pa d ma shri Ra sto g i, M.D. VA EAST ERN COL ORADO HEAL T H C ARE SYST E M: Ro b e rt K e ith, M.D. DURHAM VA ME DI CAL CENT E R: Willia m Ya nc y, M.D. N. FL / S. G A VE T E RANS HEAL T H

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SYST E M: Pe ruve mb a Srira m, M.D. HAMPT ON VA ME DI CAL CENT E R: Ma rine ll Mumfo rd , Ph.D.; Pra n I ruva nti, D.O., Ph.D. E DWARD HI NE S, JR. VA HOSPI T AL : Sa lva d o r Gutie rre z, M.D. MI CHAEL E . DE BAKE Y VA ME DI CAL CE NT ER: Ra ya n Al Jurdi, M.D.; L a ura Ma rsh, M.D. RI CHARD ROUDE BUSH VA ME DI CAL CE NT ER: Jo hn Ca lla g ha n, M.D., Ph.D.; T ho ma s Sha rp, M.D. KANSAS CI T Y VA ME DI CAL CE NT E R: Pra sha nt Pa ndya , D.O.; T ho ma s De ma rk, M.D. VA EAST ERN KANSAS HEAL T H C ARE SYST E M: Ma ry Oe hle rt, Ph.D. CE NT RAL ARKANSAS VE T E RANS HEAL T H C ARE SYST E M: K. Da vid Stra ub , M.D., Ph.D.; Sue T he us, Ph.D. VA L OMA L I NDA HEAL T HC ARE SYST E M: Ro na ld F e rna ndo , M.D. VA L ONG BEACH HEAL T HC ARE SYST E M: T imo thy Mo rg a n, M.D. VA GREAT ER L OS ANGE L ES HE AL T H C ARE SYST E M: Ag ne s Wa llb o m, M.D., M.S. WI L L IAM S. MI DDL E T ON ME MORIAL VE T E RANS HOSPI T AL : Ro b e rt Strike r, M.D., Ph.D. VA MAINE HEAL T HC ARE SYST E M: Ra y L a sh, M.D., F.A.C.P. VA ME DI CAL CE NT E R MANC HE ST E R: No ra Ra tc liffe , M.D. VA NE W YORK HARBOR HEAL T HCARE SYST E M: Sc o tt She rma n, M.D., M.P.H. ME MPHI S VA ME DI CAL CE NT ER: Ric ha rd Childre ss, M.D.; Ma rsha ll E la m, M.D., Ph.D. MIAMI VA HEAL T H CARE SYST E M: He rme s F lo re z, M.D., Ph.D. CL E ME NT

J. ZABL

OCK I VA ME DI CAL CE NT E R: Je ff Whittle , M.D., M.P.H. MI NNEAPOL I S VA HEAL T H CARE SYST E M: F ra nk A. L e d e rle , M.D. VA T E NNESSE E VAL L E Y HEAL T HCARE SYST E M: Adria na Hung , M.D., M.P.H.; Je ffre y Smith, M.D., Ph.D. CENT RAL WE ST E RN MASSACHUSE T T S HEAL T HCARE SYST E M: K ristin Ma tto c ks, Ph.D., M.P.H. ORL ANDO VA ME DI CAL CENT ER: K e nne th Go ldb e rg , M.D.; Ada m Go lde n, M.D. VA PAL O AL T O HEAL T H C ARE SYST E M: Philip T sa o , Ph.D. PHI L ADE L PHIA VA ME DI CAL CE NT E R: Da rsha na Jha la , M.D.; K yo ng -Mi Cha ng , M.D. PHOENI X VA HEAL T H C ARE SYST EM: Sa mue l Ag ua yo , M.D. VA PI T T SBURGH HEAL T H CARE SYST E M: E lif So ne l, M.D.; Gre tc he n Ha a s, Ph.D. PORT L AND VA ME DI CAL CE NT E R: Da vid Co he n, M.D. RI CHMOND VA ME DI CAL CE NT E R: Mic ha e l Go dsc ha lk, M.D. W.G. (BI L L ) HE F NE R VA ME DI CAL CE NT E R: Ro b in Hurle y, M.D. VA SAL T L AKE CI T Y HE AL T H C ARE SYST E M: L a ure nc e Me ye r, M.D., Ph.D.; Vic kie Ve nne , M.S. SOUT H T E XAS VE T E RANS HEAL T H C ARE SYST E M: Sunil Ahuja , M.D.; Ja c q ue line Pug h, M.D. VA SAN DI E GO HEAL T HC ARE SYST E M: Gwe n Ande rso n, Ph.D., R.N. VA C ARI BBEAN HEAL T HCARE SYST E M: Ca rlo s Ro sa do -Ro drig ue z, M.D.; Willia m Ro drig ue z, M.D. VA PUGE T SOUND HEAL T H C ARE SYST E M: E d wa rd Bo yko , M.D.; K a rin Ne lso n, M.D. OVE RT ON BROOKS VA ME DI CAL CENT E R: Ro na ld Wa shb urn, M.D. ST . L OUI S VA HEAL T H CARE SYST E M: Mic ha e l Ra uc hma n, M.D. JAME S A. HAL E Y VE T E RANS’ HOSPI T AL : Ste phe n Ma sto ride s, M.D.; L a ure n De la nd, R.N., M.P.H. SOUT HE RN ARI ZONA VA HEAL T H C ARE SYST E M: Ro na ld Sc hifma n, M.D.; Ste phe n T ho mso n, M.D. T USCAL OOSA VA ME DI CAL CE NT E R: L

ri Da vis, M.D.; Pa tric ia Pilkinto n, M.D. WASHI

NGT ON DC VA ME DI CAL CE NT E R: Ayma n F a no us, M.D. VA CONNE CT I CUT HEAL T H C ARE SYST E M: Da nie l F e de rma n, M.D. WHI T E RI VE R JUNCT I ON VA ME DI CAL CENT E R: Bro o ks Ro b e y, M.D.

Obje c tive s:

T he ma in o b je c tive o f MVP is to impro ve unde rsta nding o f ho w g e ne tic c ha ra c te ristic s, b e ha vio rs, a nd e nviro nme nta l fa c to rs c o mb ine to a ffe c t he a lth. Ultima te ly, the inte nt is to e nha nc e the c a re o f the Ve te ra n pa tie nt po pula tio n b y pro viding a fra me wo rk fo r sc ie ntific a lly va lid a nd c linic a lly re le va nt g e no mic me dic ine . Ve te ra ns who vo lunte e r pro vide a b lo o d sa mple fo r b io b a nking a nd re spo nse s to q ue stio nna ire s; the y a lso c o nse nt to a llo w a c c e ss to c linic a l da ta fro m VA e le c tro nic he a lth re c o rds a nd o the r so urc e s suc h a s NDI , CMS a nd DOD, a nd to b e ing re -c o nta c te d b y MVP sta ff fo r (po te ntia l) furthe r da ta c o lle c tio n o r future studie s.

F unding Pe r iod and FY14 T

tal: Co ntinuo usly funde d sinc e 2010

Cur r e nt Intr a-Pr

am Wo r king Gr

ups: Se e Co mmitte e struc ture a b o ve .

Majo r Collabo r ations and T he ir Goals:

T he e sta b lishme nt o f the re so urc e s a nd se ve ra l funde d te st pro je c ts a re c o nduc te d la rg e ly b y VA I nve stig a to rs a nd

the r e mplo ye e s a nd o the rs a t a ffilia te d a c a de mic institutio ns. T

wo la rg e -sc a le te st pro je c ts a re in the a re a o f me nta l he a lth.

Re so ur c e s and T

o ls Pr
duc e d:

MVP b a se line a nd life style q ue stio nna ire Auto ma te d sa mple pro c e ssing fa c ility Auto ma te d b io spe c ime ns sto ra g e fa c ility Da ta b a se with 380,000 e nro lle e s Phe no mic s c o re I nfo rma tic s c o re

F ive Ke y Public atio ns: De sig n pa pe r sub mitte d

SLIDE 61

Majo r Obstac le s and Ne e ds that Might be F ac ilitate d by G e no mic Me dic ine Re se ar c h: Ma jor Obsta c le s a nd Ne e ds Approa c he s Conside re d or Propose d to O ve rc ome Obsta c le s

w c o st se q ue nc ing a nd o the r o mic s

Co ntra c t o r c o lla b o ra tio n L

w c o st pro c e ssing o f se q ue nc e da ta

Co ntra c t o r c o lla b o ra tio n Upg ra de d inte rna l HPC se c ure d in VA Co ntra c t Clo ud c o mp uting e nviro nme nt Ho ste d b y o utside ve nde r via c o ntra c t Syste m to e na b le a c c e ss b y ma ny use rs Built b y inte rna l info rma tic s te a m a nd/ o r c o ntra c te d

NCI Pr

am Offic ials: VA Pro g ra m Offic ia l: Dr. T

im O’ L e a ry, CRADO, VA Ce ntra l Offic e , Wa shing to n, DC

SLIDE 62

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am NCI-AL CHE MIST

Pro g ram Name and We b site : AL CHE MI ST (Adjuva nt L ung Ca nc e r E nric hme nt Ma rke r I de ntific a tio n a nd Se q ue nc ing T ria l )(http:/ / dc td.c a nc e r.g o v/ Ma jo rI nitia tive s/ NCI

spo nso re d_tria ls_in_pre c isio n_me dic ine .htm)

PI s and Funde d Site s: up to 2400 c linic al site s thru Natio nal Clinic al T rials Ne two rk, le d b y E COG-ACRI N (Bo b Co mis MD), AL L I ANCE (Mo nic a Be rtag no lli MD) T wo CL I A ac c re dite d lab site s fo r se q ue nc ing E GF R and fo r F I SH fo r AL K translo c atio n; Ce nte r fo r Canc e r Ge no mic s and T CGA Se q ue nc ing and Charac te rizatio n c e nte rs fo r e xplo rato ry g e no mic s (who le e xo me , RNA se q , who le g e no me )

Obje c tive s:

Ob se rva tio na l tria l fo r tho se 85% o r so tha t do no t ha ve a c tiva ting E GF R muta tio ns o r AL K re a rra ng e me nts. T his re se a rc h tria l studie s g e ne tic te sting in sc re e ning pa tie nts with sta g e I B-I I I A no n-sma ll c e ll lung c a nc e r tha t ha s b e e n

r will b e re mo ve d b y surg e ry. Studying the g e ne s in a pa tie nt's tumo r c e lls ma y he lp do c to rs se le c t the b e st

tre a tme nt fo r pa tie nts tha t ha ve c e rta in g e ne tic c ha ng e s. I f pa tie nts ha ve E GFR a c tiva ting muta tio ns o r AL K re a rra ng e me nts the y will b e o ffe re d pa rtic ipa tio n in the re le va nt ra ndo mize d pha se 3 tria l o f sta nda rd tre a tme nt with o r witho ut the re le va nt ta rg e te d tre a tme nt:

Sc re e n 6000-8000 pa tie nts
E

pide mio lo g y/ e xp o sure q ue stio nna ire

re pro file a t re la pse
c o lle c tio n o f pla sma fo r c tDNA
Pub lic re so urc e fo r re se a rc h c o mmunity with g e no mic c ha ra c te riza tio n tie d to de ta ile d c linic a l a nno ta tio n,

e pide mio lo g ic da ta , lo ng te rm o utc o me da ta (Ge no mic Da ta Co mmo ns)

F unding Pe r iod and FY14 T

tal: no t a gr

ant, but use s se ve r al gr ants and c o ntr ac t Cur r e nt Intr a-Pr

am Wo r king Gr

ups: Ste e ring c o mmitte e ; I

DSC

Majo r Collabo r ations and T he ir Goals: NCT N; NCORP (NCI supporte d c linic a l tria ls g roups) NCI supporte d c a nc e r c e nte rs Re so ur c e s and T

o ls Pr
duc e d: no ne to date

F ive Ke y Pub lic atio ns: 1. Ge rb e r DE, Oxna rd GR, Go vinda n R. AL CHE MI ST : Bring ing g e no mic disc o ve ry a nd ta rg e te d the ra pie s to e a rly- sta g e lung c a nc e r. Clin Pha rma c o l T he r. 2015 Ma y;97(5):447-50 2. Ab ra ms J, Co nle y B, Mo o ne y M e t a l. Na tio na l Ca nc e r I nstitute 's Pre c isio n Me dic ine I nitia tive s fo r the ne w Na tio na l Clinic a l T ria ls Ne two rk. Am So c Clin Onc o l E duc Bo o k. 2014:71-6. do i: 10.14694/ E dBo o k_AM.2014.34.71.

Majo r Obstac le s and Ne e ds that Might be F ac ilitate d by G e nomic Me dic ine Re se ar c h: Ma jor Obsta c le s a nd Ne e ds Approa c he s Conside re d or Propose d to O ve rc ome Obsta c le s

NONE

NCI Pr

am Offic ials: Je ff Abr ams MD; Shakun Malik MD; & Me g Mo one y MD

SLIDE 63

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am NCI-MAT CH

Pro g ram Name and We b site : NCI

CH (Mo le c ula r a na lysis fo r the ra py c ho ic e ) will b e po ste d to c linic a ltria ls.g o v

nc e a c tiva te d (http:/ / d c td.c a nc e r.g o v/ Ma jo rI

nitia tive s/ NCI

spo nso re d_tria ls_in_pre c isio n_me dic ine .htm)

PI s and Funde d Site s: up to 2400 c linic al site s thru Natio nal Clinic al T rials Ne two rk, le d b y E COG-ACRI N (Bo b Co mis MD) F

ur CL

I A ac c re dite d lab site s fo r NGS: Yale (Je ff Sklar MD), MDAnde rso n Canc e rCe nte r (Stan Hamilto n MD), Massac huse tts Ge ne ral Ho spital (A. Jo hn I afrate MD) and the Mo le c ular Charac te rizatio n L ab o rato ry at the F re de ric k Natio nal L ab o rato ry fo r Canc e r Re se arc h (PM Williams PhD)

Prima ry Obje c tive :

T
e va lua te the pro po rtio n o f pa tie nts with o b je c tive re spo nse (OR) to ta rg e te d study a g e nt(s) in p a tie nts with

a dva nc e d re fra c to ry c a nc e rs/ lympho ma s.

Se c onda ry Obje c tive s

T
e va lua te the pro po rtio n o f pa tie nts a live a nd pro g re ssio n fre e a t 6 mo nths o f tre a tme nt with ta rg e te d study

a g e nt in pa tie nts with a dva nc e d re fra c to ry c a nc e rs/ lympho ma s.

T
e va lua te time until de a th o r dise a se pro g re ssio n.
T
ide ntify po te ntia l pre dic tive b io ma rke rs b e yo nd the g e no mic a lte ra tio n b y whic h tre a tme nt is a ssig ne d o r

re sista nc e me c ha nisms using a dditio na l g e no mic , RNA a nd pro te in-b a se d a sse ssme nt pla tfo rms.

F unding Pe r iod and FY14 T

tal: no t a gr

ant, but use s se ve r al gr ants and c o ntr ac ts Cur r e nt Intr a-Pr

am Wo r king Gr

ups:

Ste e ring c o mmitte e ; Ag e nts/ Ge ne s wo rking g ro up ; Sa mple s/ se q ue nc ing wo rking g ro up; I nfo rma tic s wo rking g ro up ; I nc ide nta l finding s/ e thic s wo rking g ro up ; I ma g ing wo rking g ro up ; Re g ula to ry wo rking g ro up

Majo r Collabo r ations and T he ir Goals: NCT N; NCORP (NCI supporte d c linic a l tria ls g roups) NCI supporte d c a nc e r c e nte rs Re so ur c e s and T

o ls Pr
duc e d: no ne to date

F ive Ke y Public atio ns:

1. Co nle y BA, Do ro sho w JH. Mo le c ula r a na lysis fo r the ra py c ho ic e : NCI MAT

CH. Se min Onc o l. 2014 Jun;41(3):297-9.

2. K umma r S, Willia ms PM, L ih C-H e t a l. Applic a tio n o f mo le c ula r pro filing in c linic a l tria ls fo r a dva nc e d me ta sta tic c a nc e r. J Na tl Ca nc e r I

nst. 2015; 107(4) o nline

Majo r Ob stac le s and Ne e ds that Mig ht b e F ac ilitate d b y Ge no mic Me dic ine Re se arc h:

Ma jor Obsta c le s a nd Ne e ds Approa c he s Conside re d or Propose d to O ve rc ome Obsta c le s

NONE

NCI Pr

am Offic ials: Bar bar a Conle y MD; Je ff Ab r ams MD; & Alic e Che n MD

SLIDE 64

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am PAGE

Pro g ram Name and We b site : Po p ula tio n Arc hite c ture using Ge no mic s a nd E pide mio lo g y (PAGE) Co nso rtium, https:/ / pa g e study.o rg / PI s and Funde d Site s: Christo phe r Ha ima n, L

ic L

e Ma rc ha nd Unive rsity o f So uthe rn Ca lifo rnia / Multie thnic Co ho rt Study Ruth L

Mo unt Sina i Sc ho o l o f Me dic ine / I nstitute fo r Pe rso na lize d Me dic ine (I PM) Bio Me Bio b a nk K a ri No rth Unive rsity o f No rth Ca ro lina , Cha pe l Hill / Ge ne tic E pide mio lo g y o f Ca usa l Va ria nts Ac ro ss the L ife Co urse (C AL iCo ) Cha rle s Ko o pe rb e rg F re d Hutc hinso n Ca nc e r Re se a rc h Ce nte r/ Wo me n’ s He a lth I nitia tive T a ra Ma tise , Ste ve Buyske Rutg e rs Unive rsity / Co o rdina ting Ce nte r K im Do he ny, Ja ne Ro mm Ce nte rs fo r I nhe rite d Dise a se Re se a rc h (g e no typing )

Obje c tive s:

1. E xa mine puta tive c a usa l g e ne tic va ria nts a c ro ss a ppro xima te ly 100,000 Afric a n Ame ric a ns, Asia n Ame ric a ns, Ame ric a n I ndia ns, E uro p e a n Ame ric a ns, Hispa nic Ame ric a ns, a nd Na tive Ha wa iia ns fro m fo ur studie s re pre se nting se ve n la rg e U.S.-b a se d c o ho rts with e xte nsive da ta o n a ra ng e o f tra its a nd dise a se re le va nt to huma n he a lth (PAGE 1). 2. Pro vide suppo rt fo r inve stig a to rs to sa mple a nd a sse ss g e no mic va ria tio n fro m o ve r 50,000 we ll-phe no type d individua ls o f no n-E uro pe a n (EA) a nc e stry a nd disse mina te the re sulting da ta to fo rm a po p ula tio n re so urc e tha t will e xpa nd unde rsta nding o f a nc e stra l diffe re nc e s in g e no mic dise a se a sso c ia tio ns (PAGE 2).

F unding Pe r iod and FY14 T

tal: F

Y2008-F Y2016, $7.47M (F Y2014)

Cur r e nt Intr a-Pr

am Wo r king Gr

ups:

1. Ana lysis 2. Anthro p o me tric s 3. Arra y de sig n a nd sa mple s 4. CHD/ ECG 5. Clinic a lly re le va nt va ria nts 6. Hype rte nsio n/ kidne y 7. I nfla mma tio n 8. L ife style / re pro d uc tio n 9. L ipids

10. T

ype 2 dia b e te s

Majo r Collabo r ations and T he ir Goals:

Co nso rtium o n Asthma a mo ng Afric a n-a nc e stry Po pula tio ns in the Ame ric a s (C AAPA): de sig n o f ME

GA a rra y (se e b e lo w)

Re sour c e s and T

o ls Pr
duc e d:

1. Multi-E thnic Ge no typing Arra y (ME G A): I llumina g e no typing a rra y fe a turing c o mmo n a nd ra re va ria tio n se le c te d fo r a nc e stra lly dive rse po p ula tio ns (http:/ / www.c idr.jhmi.e d u/ suppo rte d/ 20140729_ME GA_Custo me rFAQ_to %20(3)_E DI T E D_JMR.pdf) 2. db Ga P sub missio ns (http:/ / www.nc b i.nlm.nih.g o v/ g a p? te rm=PAGE %5BStud y%20Na me %5D)

F ive Ke y Public atio ns:

1. Ma tise T C, e t a l. T he Ne xt PAGE in unde rsta nding c o mple x tra its: de sig n fo r the a na lysis o f Po pula tio n Arc hite c ture Using Ge ne tic s a nd E pide mio lo g y (PAGE) Stud y. 2011; Am J Epide mio l 174, 849-859. PMI D 21836165. 2. Go ng , J, e t a l. F ine Ma pping a nd I de ntific a tio n o f BMI L

c i in Afric a n Ame ric a ns. 2013; Am J Hum Ge ne t;

93(4):661. PMI D 24094743. 3. Ca rlso n CS, e t a l. Ge ne ra liza tio n a nd dilutio n o f a sso c ia tio n re sults fro m E uro pe a n GWAS in po p ula tio ns o f no n- E uro pe a n a nc e stry: the PAGE stud y. 2013; PL

S Bio l. 11(9):e 1001661. PMI

D 24068893. 4. Pa rk SL , e t a l. Asso c ia tio n o f the F T O o b e sity risk va ria nt rs8050136 with pe rc e nta g e o f e ne rg y inta ke fro m fa t in multiple ra c ia l/ e thnic po pula tio ns: the PAGE stud y. 2013; Am J E pide mio l. 178(5):780. PMI D 23820787. 5. Buyske S, e t a l. E va lua tio n o f the me ta b o c hip g e no typing a rra y in Afric a n Ame ric a ns a nd implic a tio ns fo r fine ma pping o f GWAS-ide ntifie d lo c i: the PAGE stud y. 2012; PL

S One 7, e 35651. PMI

D 22539988.

SLIDE 65

Majo r Obstac le s and Ne e ds that Might be F ac ilitate d by G e no mic Me dic ine Re se ar c h: Ma jor Obsta c le s a nd Ne e ds Approa c he s Conside re d/ Propose d to O ve rc ome Obsta c le s

I nte g ra te a nc e stra lly dive rse individua ls into g e no mic me dic ine re se a rc h F

c us o n re c ruiting , a na lyzing , a nd c o mmunic a ting with dive rse individua ls

a nd the ir he a lthc a re pro vide rs. Build o n e xta nt c o lle c tio ns o f we ll- c ha ra c te rize d a nd a nc e stra lly dive rse c o ho rts fo r pe rso na lize d me dic ine re se a rc h. I mpro ve ide ntific a tio n a nd inte rpre ta tio n o f c linic a lly re le va nt va ria nts fo r a nc e stra lly dive rse individua ls Be a wa re o f diffe re nc e s in a lle le fre q ue nc ie s o f c linic a lly re le va nt va ria nts a mo ng a nc e stra l po pula tio ns, a nd hig hlig ht whe n suc h fre q ue nc ie s a re no t kno wn. F a c ilita te c o lle c tio n a nd sta nda rdiza tio n o f la rg e -sc a le phe no typing da ta de rive d fro m he te ro g e ne o us so urc e s L e a rn fro m a nd c o ntrib ute to e xisting phe no type ha rmo niza tio n e ffo rts. Bro a de n e ffo rts to ha rmo nize phe no type s a c ro ss multiple mo da litie s (e .g , mHe a lth, E HR, surve ys). Fa c ilita te c o lla b o ra tio n a mo ng la rg e c o ho rts with he te ro g e ne o us so urc e s o f phe no type da ta . NHGRI Pro g ram Offic ials: L uc ia Hindo rff

SLIDE 66

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am PCORne t

Pro g ram Name and We b site : PCORNe t (PCORI funde d initia tive ): http:/ / www.pc o rne t.o rg / I nc lude s 11 Clinic a l Da ta Re se a rc h Ne two rks (CDRNs), 18 Pa tie nt Po we re d Re se a rc h Ne two rks (PPRNs), a nd a Co o rdina ting Ce nte r (Ha rva rd, Duke ; CO-PI s Ric ha rd Pla tt a nd Adria n He rna nde z)

PIs and F unde d Site s: CDRNS:

PPRNS:

Obje c tive s:

Cre a te a se c ure na tio na l re se a rc h re so urc e tha t will e na b le te a ms o f he a lth re se a rc he rs, pa tie nts, a nd the ir

pa rtne rs to wo rk to g e the r o n re se a rc hing q ue stio ns o f sha re d inte re st 2.

Utilize multiple ric h da ta so urc e s to suppo rt re se a rc h, suc h a s e le c tro nic he a lth re c o rds, insura nc e c la ims da ta ,

a nd da ta re po rte d dire c tly b y pa tie nts 3.

E ng a g e pa tie nts, c linic ia ns & he a lth syste m le a de rs thro ug ho ut the re se a rc h c yc le fro m ide a g e ne ra tio n to

imple me nta tio n 4.

Support o b se rva tio na l a nd inte rve ntio na l re se a rc h studie s tha t c o mpa re ho w we ll diffe re nt tre a tme nt o ptio ns

wo rk fo r diffe re nt pe o ple 5.

E na ble e xte rna l pa rtne rs to c o lla b o ra te with PCORI

funde d ne two rks

Susta in PCORne t re so urc e s fo r a ra ng e o f re se a rc h a c tivitie s suppo rte d b y PCORI

a nd o the r spo nso rs

F unding Pe r iod and FY14 T

tal:

PCORI ha s c o mmitte d o ve r $250 millio n to da te to wa rds PCORne t inc luding : PHASE I : I nitia l 18 mo nths (Ja nua ry 2014-July 2015) 11 CDRNs a t $7 millio n e a c h = $77 millio n 18 PPRNs a t $1 millio n e a c h = $18 millio n Co o rdina ting Ce nte r a t ~ $12 millio n PHASE I I : 36 mo nths (~ July 2015-July 2018) 13 CDRNs a t ~$8.75 millio n e a c h = $114 millio n

SLIDE 67

22 PPRNs a t ~$1 millio n e a c h = $22 millio n Co o rdina ting Ce nte r a t ~ $14 millio n T RIAL S ADAPT ABL E (ASA T RIAL ): $14 millio n Ob e sity Ob se rva tio na l T ria ls: $9 millio n

Majo r Collabo r ations and T he ir Goals:

1. F DA Mini-Se ntine l/ Se ntine l Ne two rk: Simila r c o mmo n da ta mo de l a nd pa rtic ipa tio n o f CDRNs in Se ntine l ne two rk. 2. E me rg e : Sha ring Co mputa b le phe no type s o n the Phe K B we b site 3. CT SA Co nso rtium: Use o f I RBsha re , ACT A, RE DCa p, a nd o the r CT SA c o nso rtia to o ls

Re so ur c e s and T

o ls Pr
duc e d:

1. De ve lo pme nt o f PCORne t Co mmo n Da ta Mo de l 2. T

o ls fo r e le c tro nic ide ntific a tio n a nd c o nta c t o f pa tie nts using RE

DCa p inc luding e -c o nse nt, a nd e le c tro nic surve y via we b o r mo b ile te c hno lo g y 3. I nte g ra tio n o f PROMI S me a sure s into RE DCa p 4. De ve lo pme nt o f ne two rk-wide po lic ie s re la te d to da ta sha ring , I RB, a nd c o ntra c ting

F ive Ke y Public atio ns:

1. F le ure nc e RL , Curtis L H, Ca liff RM, Pla tt R, Se lb y JV, Bro wn JS. L a unc hing PCORne t, a na tio na l pa tie nt-c e nte re d c linic a l re se a rc h ne two rk. Jo urnal o f the Ame ric an Me dic al I nfo rmatic s Asso c iatio n : JAMI

A. 2014;21(4):578-582.

do i:10.1136/ a mia jnl-2014-002747. 2. PCORne t PPRN Co nso rtium, Da ug he rty SE

1, Wa hb a S 1, F

le ure nc e R1., Pa tie nt-po we re d re se a rc h ne two rks: b uilding c a pa c ity fo r c o nduc ting pa tie nt-c e nte re d c linic a l o utc o me s re se a rc h.J Am Me d I nfo rm Asso c . 2014 Jul-Aug ;21(4):583-6. d o i: 10.1136/ a mia jnl-2014-002758. E pub 2014 3. Wa itma n L R, Aa ro nso n L S, Na dka rni PM, Co nno lly DW, Ca mpb e ll JR. T he Gre a te r Pla ins Co lla b o ra tive : a PCORne t Clinic a l Re se a rc h Da ta Ne two rk.Jo urnal o f the Ame ric an Me dic al I nfo rmatic s Asso c iatio n : JAMI A. 2014;21(4):637-641. d o i:10.1136/ a mia jnl-2014-002756. 4. Ro se nb lo o m, S. T ., Ha rris, P., Pulle y, J., Ba sfo rd , M., Gra nt, J., DuBuisso n, A., & Ro thma n, R. L . (2014). T he Mid - So uth Clinic a l Da ta Re se a rc h Ne two rk.Jo urnal o f the Ame ric an Me dic al I nfo rmatic s Asso c iatio n : JAMI A, 21(4), 627–632. d o i:10.1136/ a mia jnl-2014-002745 5. K ho AN, Hyne s DM, Go e l S, e t a l. CAPriCORN: Chic a g o Are a Pa tie nt-Ce nte re d Outc o me s Re se a rc h Ne two rk. Jo urnal o f the Ame ric an Me dic al I nfo rmatic s Asso c iatio n : JAMI

A. 2014;21(4):607-611.

do i:10.1136/ a mia jnl-2014-002827.

Majo r Obstac le s and Ne e ds that Might be F ac ilitate d by G e no mic Me dic ine Re se ar c h: Ma jor Obsta c le s a nd Ne e ds Approa c he s Conside re d or Propose d to O ve rc ome Obsta c le s

L inka g e o f c linic a l E HR da ta to b io re po sito ry da ta Use o f de -ide ntifie d da ta linka g e (e x. Bio Vu). Ne e d to a ddre ss pa tie nt c o nse nt/ priva c y issue s. Co st o f a dditio na l g e no mic da ta . T ra nsfo rma tio n o f b io re p o sito ry da ta into sta nda rdize d da ta fo r PCORne t c o mmo n da ta mo de l Va lida tio n o f phe no type s Sha ring o f c o mp uta b le phe no type s via Phe K B

SLIDE 68

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am PGRN

Pro g ram Name and We b site : Pha rma c o g e no mic s Re se a rc h Ne two rk (PGRN), http:/ / pg rn.o rg / displa y/ p g rnwe b site / PGRN+Ho me

PIs and F unde d Site s:

K e nne th E . T humme l, Ph.D. a nd Wylie Burke , M.D. Ph.D. NWAP: Pha rma c o g e ne tic s in Rura l a nd Unde rse rve d Po pula tio n Ma rk J. Ra ta in, M.D., Na nc y J. Co x, Ph.D.

M. E

ile e n Do la n, Ph.D. PAAR: Pha rma c o g e no mic s o f Antic a nc e r Ag e nts Re se a rc h Gro up Ma ry V. Re lling , Pha rm.D. PAAR4K ids: Pha rma c o g e no mic s o f Antic a nc e r Ag e nts Re se a rc h in Childre n Ala n R. Shuldine r, M.D. PAPI

2: Pha rma c o g e no mic s o f Anti-Pla te le t

I nte rve ntio n-2 (PAPI

2) Study

Ro na ld M. K ra uss, M.D. PARC: Pha rma c o g e no mic s a nd Risk o f Ca rdio va sc ula r Dise a se Da n M. Ro de n, M.D. PAT : Pha rma c o g e no mic s o f Arrhythmia T he ra py Julie A. Jo hnso n, Pha rm.D., Rho nda Co o pe r-De Ho ff, Pha rm.D. PEAR: Pha rma c o g e no mic E va lua tio n o f Antihype rte nsive Re spo nse s Jo hn R. Ke lso e , M.D. PGBD: Pha rma c o g e no mic s o f Mo o d Sta b ilize r Re sp o nse in Bipo la r Diso rde r Sc o tt T . We iss, M.D., M.S., K e la n G. T a ntisira , M.D. PHAT : Pha rma c o g e ne tic s o f Asthma T re a tme nt So umya Ra yc ha udhuri , M.D., a nd Mic ha e l Bre nne r, M.D. PhRAT : Pha rma c o g e no mic s o f Rhe uma to id Arthritis T he ra py K a thle e n M. Gia c o mini, Ph.D. PMT : Pha rma c o g e ne tic s o f Me mb ra ne T ra nsp o rte rs Ca ryn L e rma n, Ph.D., a nd Ra c he l T ynda le , Ph.D. PNAT : Pha rma c o g e ne tic s o f Nic o tine Addic tio n T re a tme nt Ric ha rd M. We inshilb o um, M.D., a nd L ie we i Wa ng , M.D., Ph.D. PPI I : Pha rma c o g e ne tic s o f Pha se I I Drug Me ta b o lizing E nzyme s Wo lfg a ng Sa de e , Dr.re r.na t. XGE N: E xpre ssio n Ge ne tic s in Drug T he ra p y

Obje c tive s:

T he PGRN is a ne two rk o f sc ie ntific g ro ups who se visio n is to le a d disc o ve ry a nd a dva nc e tra nsla tio n in g e no mic s, to e na b le sa fe r a nd mo re e ffe c tive drug the ra pie s. I t ha s b e e n supp o rte d sinc e 2000 b y the NI

H. I

ts o b je c tive s a re to :

Co nd uc t studie s in b a sic , tra nsla tio na l, a nd c linic a l sc ie nc e to a dva nc e the sc ie ntific visio n
De ve lo p no ve l e xpe rime nta l me tho ds a nd to o ls to so lve pha rma c o g e no mic pro b le ms
Sha re da ta a nd, whe re fe a sib le , b io lo g ic a l sa mple s in c o lla b o ra tio ns
F
ste r c ro ss-disc iplina ry te a ms fo r disc o ve ry a nd disse mina tio n o f ne w info rma tio n
Build e ffe c tive pa rtne rships a nd a llia nc e s with ke y sta ke ho lde rs o utside the PGRN
E

ng a g e re la te d disc ipline s to a dva nc e the a pplic a tio n o f pha rma c o g e no mic kno wle dg e

Wo rk to g e the r to ma ke the ne two rk b e c o me mo re tha n the sum o f the pa rts

F unding Pe r iod and FY14 T

tal: F

Y2000-F Y2015, re ne wa l unde r c o nside ra tio n: the ne two rk is unde rg o ing tra nsitio n; se e the PGRN T ra nsitio n Pla ns

Cur r e nt Intr a-Pr

am Wo r king Gr

ups:
P-ST

AR – PGRN Sta tistic a l Ana lysis Re so urc e

PG-POP – Pha rma c o Ge no mic disc o ve ry a nd re plic a tio n in ve ry la rg e pa tie nt POPula tio ns
PHONT

– PGRN Onto lo g y Ne two rk Re so urc e

De e p Se q ue nc ing Re so urc e s: BCM-HGSC (Ba ylo r), UW-NE

XT GE N – Unive rsity o f Wa shing to n, WU-NGS – Wa shing to n Unive rsity

Majo r Collabo r ations and T he ir Goals:

Pha rmGK

B – Pha rma c o g e no mic s K no wle dg e Ba se www.pha rmg kb .o rg / inde x.jsp

PGRN-CGM – Pha rma c o g e no mic s Re se a rc h Ne two rk & Ce nte r fo r Ge no mic Me dic ine Glo b a l Allia nc e (with

RI K E N Ce nte r fo r Ge no mic Me dic ine ) http:/ / pg rn.o rg / displa y/ pg rnwe b site / PGRN-CGM+Pro file

SLIDE 69

C—Clinic a l Pha rma c o g e ne tic s I mple me nta tio n Co nso rtium https:/ / www.pha rmg kb .o rg / pa g e / c pic

Re so ur c e s and T

o ls Pr
duc e d:

1. Pha rmGK B – Pha rma c o g e no mic s K no wle dg e Ba se www.pha rmg kb .o rg / inde x.jsp 2. T ra nsla tio na l Sc ho la r Ca re e r Awa rd s: http:/ / www.nig ms.nih.g o v/ Re se a rc h/ Spe c ific Are a s/ PGRN/ CT SAsc ho la rs/ Pa g e s/ de fa ult.a spx 3. Re se a rc h in Pro g re ss Se mina rs: http:/ / pg rn.o rg / displa y/ pg rnwe b site / PGRN-RI PS+Sc he dule 4. Pro je c ts: PGRNSe q / PGxSe q Pro je c t; T ra nsla tio na l Pha rma c o g e ne tic s Pro je c t; Po lyg e nic Mo de ling Pro je c t; RNA Se q Pro je c t http:/ / pg rn.o rg / displa y/ pg rnwe b site / Ne two rk-wide +Pro je c ts

F ive Ke y Public atio ns:

1. Dio uf B, Cre ws KR, L e w G, Pe i D, Che ng C, Ba o J, Zhe ng JJ, Ya ng W, F a n Y, Whe e le r HE , Wing C, De la ne y SM, K

ma tsu M, Pa ug h SW, Mc Co rkle JR, L

u X, Winic k NJ, Ca rro ll WL , L

h ML

, Hung e r SP, De vida s M, Pui C-H, Do la n ME , Re lling MV, E va ns WE . Asso c ia tio n o f a n I nhe rite d Ge ne tic Va ria nt with Vinc ristine -Re la te d Pe riphe ra l Ne uro pa thy in Childre n with Ac ute L ympho b la stic L e uke mia . JAMA. 2015 F e b 24;313(8):815-23. PMI D: 25710658 2. Pe re ra MA, Ca va lla ri L H, L imdi NA, Ga ma zo n E R, Ko nka shb a e v A, Da ne shjo u R, Pluzhniko v A, Cra wfo rd DC, Wa ng J, L iu N, T a to ne tti N, Bo urg e o is S, T a ka ha shi H, Bra dfo rd Y, Burkle y BM, De snic k RJ, Ha lpe rin JL , K ha lifa SI , L a ng a e e T Y, L ub itz SA, Nute sc u EA, Oe tje ns M, Sha hin MH, Pa te l SR, Sa g re iya H, T e c to r M, We c k K E, Rie de r MJ, Sc o tt SA, Wu AH, Burme ste r JK, Wa de lius M, De lo uka s P, Wa g ne r MJ, Mushiro da T , K ub o M, Ro de n DM, Co x NJ, Altma n RB, K le in T E, Na ka mura Y, Jo hnso n JA. Ge ne tic va ria nts a sso c ia te d with wa rfa rin do se in Afric a n- Ame ric a n individua ls: a g e no me -wide a sso c ia tio n study. L a nc e t. 2013 Aug 31;382(9894):790-6. PMI D: 23755828 3. I nte rna tio na l Wa rfa rin Pha rma c o g e ne tic s Co nso rtium, K le in T E, Altma n RB, E riksso n N, Ga g e BF, K imme l SE , L e e MT , L imdi NA, Pa g e D, Ro de n DM, Wa g ne r MJ, Ca ldwe ll MD, Jo hnso n JA. E stima tio n o f the wa rfa rin do se with c linic a l a nd pha rma c o g e ne tic da ta . N E ng l J Me d. 2009 Fe b 19;360(8):753-64. PMI D: 19228618 4. Ma ng ra vite L M, E ng e lha rdt BE , Me dina MW, Smith JD, Bro wn CD, Cha sma n DI , Me c ha m BH, Ho wie B, Shim H, Na ido o D, F e ng Q, Rie de r MJ, Che n YD, Ro tte r JI , Ridke r PM, Ho pe we ll JC, Pa rish S, Armita g e J, Co llins R, Wilke RA, Nic ke rso n DA, Ste phe ns M, K ra uss RM. A sta tin-de pe nde nt QT L fo r G AT M e xpre ssio n is a sso c ia te d with sta tin- induc e d myo pa thy. Na ture . 2013 Oc t 17;502(7471):377-80. PMI D: 23995691 5. L

ng RM, Be rg JM. Wha t to e xpe c t fro m the pha rma c o g e no mic s re se a rc h ne two rk. Clin Pha rma c o l T

he r. 2011 Ma r;89(3):339-41. PMI D: 21326260

Majo r Obstac le s and Ne e ds that Might be F ac ilitate d by G e no mic Me dic ine Re se ar c h: Ma jor Obsta c le s a nd Ne e ds Approa c he s Conside re d or Propose d to O ve rc ome Obsta c le s

E nsuring tha t la rg e c linic a l studie s a nd tria ls, a s we ll a s c o ho rts b e ing de ve lo pe d , a re suita b le fo r pha rma c o g e no mic s a na lysis. T he PGRN wa nts to pro vide spe c ific , de ta ile d g uida nc e fo c use d o n drug s a nd drug re sp o nse phe no type s to ma jo r na tio na l a nd inte rna tio na l e ffo rts tha t inte nd to c re a te b io spe c ime n b a nks a nd wo rk with E MRs.

NIH Pr

am Offic ial: Ro c he lle L

ng (NI

GMS) a nd pro g ra m dire c to rs a t o the r institute s, NI H

SLIDE 70

Ge no mic Me dic ine VIII – Summar y of Re late d Pr

am PhenX

am Name and We b site : Co nse nsus Me a sure s fo r Phe no type s a nd e Xp o sure s (Phe nX), https:/ / www.phe nx.o rg PIs and F unde d Site s:

Ca ro l Ha milto n RT I I nte rna tio na l

Obje c tive s:

1. Cre a te a pub lic a nd fre e ly a va ila b le we b -b a se d c a ta lo g o f we ll-e sta b lishe d, lo w-b urde n, sta nda rd me a sure s

a nd pro to c o ls fo r use in b io me dic a l studie s.

2. E

nc o ura g e use o f sta nda rd me a sure s a nd e sta b lish c o mmo n da ta e le me nts to he lp re se a rc he rs e ffe c tive ly c o lla b o ra te , sha re da ta , a nd c o nduc t c ro ss-study a na lysis.

3. E

nha nc e Phe nX T

o lkit c o nte nt b y ide ntifying me a sure s in ne w re se a rc h do ma ins (Ra re Ge ne tic Co nditio ns,

Ob e sity, Pre g na nc y a nd Pe dia tric s) a nd e ng a g e e xpe rt re vie w pa ne ls to re visit e xisting me a sure s to e nsure the y a re still use ful.

4. E

xte nd Phe nX c a pa b ilitie s thro ug h use o f so c ia l me dia , inc lusio n o f pro to c o ls in la ng ua g e s o the r tha n E ng lish, a nd e xte nd mo de o f a d ministra tio n to inc lude we b -b a se d da ta c o lle c tio n.

5. Co lla b o ra te with o the r g ro ups tha t a re pro duc ing c o lle c tio ns o f c o mmo n d a ta e le me nts, e .g . PROMI

S a nd NI NDS CDE Pro g ra m.

6. E

ng a g e a nd e duc a te the sc ie ntific c o mmunity thro ug h e duc a tio na l we b ina rs a nd pre se nta tio ns a t sc ie ntific c o nfe re nc e s, wo rksho ps, a nd thro ug h pub lic a tio ns.

F unding Pe r iod and FY14 T

tal:
F

Y2007-F Y2014, $3.2M in FY14 ($1.2M fro m NHGRI ; c o -funding fro m NI DA a nd supple me nt funds pro vide d b y NHL BI , NI MH, a nd T RSP).

Cur r e nt Intr a-Pr

am Wo r king Gr

ups:

1. Ob e sity 2. Ra re Ge ne tic Co nditio ns 3. T ra ns-NI H Co lla b o ra tio ns a dding de pth to the Phe nX T

o lkit

a . T

b a c c o Re g ula to ry Re se a rc h (NI

H T

b a c c o Re g ula to ry Sc ie nc e Pro g ra m supple me nt)

i. Are a s o f e mpha sis: so c ia l/ c o g nitive , b io b e ha vio ra l, a g e nt, ve c to r, e nviro nme nt b . Me nta l He a lth Re se a rc h (NI MH supple me nt) i. Are a s o f e mpha sis: suic ide , PT SD c . Sub sta nc e Ab use a nd Addic tio n (NI DA supple me nt) i. Are a s o f e mpha sis: sub sta nc e use , risk fa c to rs, c o mmunity/ c o mo rb iditie s/ o utc o me s d. Sic kle Ce ll Dise a se (NHL BI supple me nt) i. Are a s o f e mpha sis: c a rdio va sc ula r, p ulmo na ry, a nd re na l c o mplic a tio ns, ne uro lo g y, q ua lity o f life a nd he a lth se rvic e s

Majo r Collabo r ations and T he ir Goals:

db Ga P: Ma pping Phe nX me a sure s to a ll c o mple te d studie s de po site d in db Ga P. Ma pping s will e na b le e a sie r

ide ntific a tio n o f db Ga P studie s tha t inc lude simila r me a sure s/ va ria b le s.

DCa p : I n c o lla b o ra tio n with RE DCa p, Phe nX is d e ve lo ping RE DCa p I nstrume nt Zip file s fo r a ll Phe nX me a sure s/ pro to c o ls. T his fe a ture will impro ve visib ility a nd upta ke o f Phe nX me a sure s b y CT SAs a nd o the r RE DCa p use rs.

Ge ne tic Allia nc e : A c ro wdso urc ing e ffo rt a ime d a t g e tting c linic ia ns to pro vide info rma tio n a b o ut the use o f

Phe nX me a sure s fo r spe c ific ra re g e ne tic c o nditio ns.

H I Cs: Se e “I ntra -Pro g ra m WGs” fo r mo re de ta ils a b o ut o ur pa rtne rships a c ro ss the NI H.

Re so ur c e s and T

o ls Pr
duc e d:

1. www.phe nxto o lkit.o rg : A da ta b a se fo r sta nda rd me a sure s re la te d to c o mple x dise a se s 2. www.phe nx.o rg : A we b po rta l tha t pro vide s info rma tio n a b o ut the pro je c t, a nd supp o rts pro je c t pa rtic ipa nts

F ive Ke y Public atio ns:

1. Sto ve r, P. J., Ha rla n, W., Ha mmo nd , J., He nde rsho t, T

., & Ha milto n, C. M. (2010). Phe nX: a to o lkit fo r inte rdisc iplina ry g e ne tic s re se a rc h. Curre nt Opinio n in L ipido lo g y, 21, 136–140.

SLIDE 71

2. Ha milto n, C. M., Stra de r, L

. C., Pra tt, J., Ma ie se , D., He nde rsho t, T ., K wo k, R., Ha mmo nd , J., Hug g ins, W., Ja c kma n, D., Pa n, H., Ne ttle s, D., Be a ty, T ., F a rre r, L ., K ra ft, P., Ma ra zita , M., Ord o va s, J., Pa to , C., Spitz, M., Wa g e ne r, D., Willia ms, M., Junkins, H., Ha rla n, W., Ra mo s, E . & Ha ine s, J. (2010) T he Phe nX T

o lkit: Ge t the Mo st F

ro m Yo ur Me a sure s. Ame ric an Jo urnal o f E pide mio lo g y. 2011 Aug 1;174(3):253-60.

3. Pa n, H., T

ryka , K., Vre e ma n, D., Hug g ins, W., Phillips, M., Me hta , J., Phillips, J., Mc Do na ld , C., Junkins, H., Ra mo s, E. & Ha milto n, C. M. (2012) Using Phe nX Me a sure s to I de ntify Oppo rtunitie s fo r Cro ss-Stud y Ana lysis. Huma n Muta tio n, 33(5), 849-857.

4. Mc Ca rty, C.A., Be rg , R., Ro ttsc he it, C.M., Wa udb y, C.J., K

itc hne r, T ., Brillia nt, M., Ritc hie , M.D. (2014) Va lida tio n o f Phe nX me a sure s in the pe rso na lize d me dic ine re se a rc h pro je c t fo r use in g e ne / e nviro nme nt studie s. BMC Me dic al Ge no mic s, 7(3), do i:10.1186/ 1755-8794-7-3

5. Mc Ca rty, C.A., Hug g ins, W., Aie llo , A.E., Bilde r, R.M., Ha riri, A., Je rnig a n, T

.L ., Ne wma n, E., Sa ng he ra , D.K., Stra uma n, T .J., Ze ng , Y., Ra mo s, E.M., Junkins, H.A. (2014) Phe nX RI SI NG: re a l wo rld imple me nta tio n a nd sha ring o f Phe nX me a sure s. BMC Me dic al Ge no mic s, 7(16), do i: 10.1186/ 1755-8794-7-16.

Majo r Obstac le s o r Ne e ds E nc o unte r e d: Ma jor Obsta c le s or Ne e ds Approa c he s to O ve rc ome Obsta c le s

I de ntifying b e st a ppro a c he s fo r ha rne ssing so c ia l me dia a nd c ro wdso urc ing me tho ds Pilo ting c ro wdso urc ing pro je c ts; Co nside ring de ve lo ping a mo de ra te d “wiki” to o b ta in fe e db a c k o n va lue a nd use o f Phe nX me a sure s I nc re a sing visib ility a nd use o f Phe nX me a sure s Phe nX pro to c o ls a va ila b le fo r uplo a d to RE DCa p; I nc lude Phe nX pro to c o ls in la ng ua g e s o the r tha n E ng lish T ra c king use o f Phe nX me a sure s in o n-g o ing studie s I mple me nte d “Re g iste r Yo ur Stud y” to ide ntify studie s using Phe nX a nd a llo w PI s o ppo rtunitie s fo r c ro ss-study c o lla b o ra tio n Mo nito ring Phe nX T

o lkit tra ffic a nd c o mmunity

a wa re ne ss Re g ula rly mo nito r we b site sta tistic s; c ha lle ng ing to g a ug e Phe nX upta ke thro ug h pub lic a tio ns a nd c ita tio ns

NHG RI Pr

am Offic ials: E

rin Ra mo s

SLIDE 72

Ge no mic Me dic ine VIII – Summar y o f Re late d Pr

am PMI

am Name and We b site : Pre c isio n Me dic ine I

nitia tive , http:/ / www.nih.g o v/ pre c isio nme dic ine /

Pr e c isio n Me dic ine Initiative Wo r king Gr

Ric ha rd L ifto n (c o -c ha ir) Ya le Unive rsity Bra y Pa tric k-L a ke (c o -c ha ir) Duke Unive rsity K a thy Hudso n (c o -c ha ir) Na tio na l I nstitute s o f He a lth E sta b a n Go nza le z Burc ha rd Unive rsity o f Ca lifo rnia , Sa n F ra nc isc o T

ny Co le s

Yuma nity T he ra pe utic s Ro ry Co llins Unive rsity o f Oxfo rd Andre w Co nra d Go o g le X Jo sh De nny Va nde rb ilt Unive rsity Susa n De smo nd-He llma n Ga te s F

unda tio n

E ric Dishma n I nte l K a thy Giusti Multiple Mye lo ma Re se a rc h F

unda tio n

Se ka r K a thire sa n Ma ssa c huse tts Ge ne ra l Ho spita l Sa c hin K he te rpa l Unive rsity o f Mic hig a n Shiriki K uma nyika Unive rsity o f Pe nnsylva nia Spe ro Ma nso n Co lo ra do Sc ho o l o f Pub lic He a lth

P. Pe a rl O’ Ro urke

Pa rtne rs He a lth Ca re Syste m Ric ha rd Pla tt Ha rva rd Pilg rim He a lth Ca re I nstitute Ja y She nd ure Unive rsity o f Wa shing to n Sue Sie g e l Ve nture s & He a lthyma g ina tio n Ro b e rt Ca liff (e x o ffic io ) F

o d a nd Drug Administra tio n

K a re n De Sa lvo (e x o ffic io ) Offic e o f the Na tio na l Co o rdina to r fo r He a lth I T Jo Ha nde lsma n (e x o ffic io ) White Ho use Offic e o f Sc ie nc e a nd T e c hno lo g y Po lic y T im O’ L e a ry (e x o ffic io ) De pa rtme nt o f Ve te ra ns Affa irs T e rry Ra uc h (e x o ffic io ) De fe nse Me dic a l Re se a rc h a nd De ve lo pme nt Pro g ra m

Obje c tive s:

1. Cre a te a la rg e re se a rc h c o ho rt o f o ne millio n o r mo re pa rtic ipa nts who c ho o se to sha re ma ny type s o f da ta (e .g ., b io me dic a l, b e ha vio ra l, a nd life style ) to a dva nc e re se a rc h 2. Use this re se a rc h c o ho rt to disc o ve r a nd q ua ntify fa c to rs tha t c o ntrib ute to illne ss, a nd te st a ppro a c he s tha t c a n pre se rve he a lth a nd tre a t dise a se 3. I nc o rpo ra te ra pidly e vo lving te c hno lo g y into the c o ho rt de sig n 4. I nvo lve pa rtic ipa nts in the pla nning , b uilding , a nd ma na g e me nt o f the c o ho rt 5. I de ntify a nd a ddre ss g a p s in e xisting po lic ie s o n d a ta priva c y, se c urity, a nd misuse tha t must b e fille d to suppo rt the PMI c o ho rt

F unding Pe r iod and FY14 T

tal: F

Y2016 (pro po se d ): $130M

Cur r e nt Intr a-Pr

am Wo r king Gr

ups:

1. Co ho rts a nd E pide mio lo g y 2. Co mmunity E ng a g e me nt a nd He a lth Dispa ritie s 3. Pa rtic ipa nt E ng a g e me nt 4. E le c tro nic He a lth Re c o rds 5. Mo b ile T e c hno lo g ie s

F ive Ke y Public atio ns:

1. Co llins FS, Va rmus H. A ne w initia tive o n pre c isio n me dic ine . N E ng l J Me d. 2015 F e b 26;372(9):793-5.

SLIDE 73

Ge no mic Me dic ine VIII: NHGRI’s Ge no mic Me dic ine Por tfo lio

June 8- 9, 2015 Hilton - Washington DC / Roc kville 1750 Roc kville Pike , Roc kville , MD 20852 (301) 468- 1100

HOT E L and T RAVE L L OGIST ICS INF ORMAT ION

ME E T ING L OCAT ION: Hilton – Washington DC / Roc kville Hote l & E xe c utive Me e ting Ce nte r 1750 Roc kville Pike Roc kville , MD 20852 T e l# (301) 468- 1100 / F ax# (301) 468- 0308 www.washingtondc r

c kville .hilton.c om

AIRPORT S: IAD - Washington Dulle s - http:/ / www.me twashair por ts.c om/ dulle s/ 208.htm DCA - Re agan National Air por t - http:/ / www.me twashair por ts.c om/ r e agan/ 1261.htm BWI - Baltimor e / Washington Inte r national Air por t - http:/ / www.bwiair por t.c om/ e n DIRE CT IONS T O T HE HIL T ON – WASHINGT ON DC / ROCKVIL L E HOT E L & E XE CUT IVE ME E T ING CE NT E R (DCA) WASHINGT ON NAT IONAL AIRPORT DIRE CT IONS

De pa rt fro m Ro nald Re a g a n Wa shing to n Na tio na l Airpo rt, VA (0.6 mi.) T a ke ra mp rig ht a nd fo llo w sig ns fo r Ge o rg e Wa shing to n Me mo ria l Pky No rth (11.7 mi.) T a ke ra mp rig ht a nd fo llo w sig ns fo r I

495 No rth (4.3 mi.)

K e e p le ft o nto I-270 N Spur (2.0 mi.) K e e p stra ig ht o nto I-270 N (0.9 mi.) K e e p rig ht to sta y o n I-270 N / Dwig ht D E ise nho we r Hwy / I

270 L
c al L

a ne s / Wa shing to n Na tio na l Pike (0.3 mi.) At e xit 4A, ta ke ra mp rig ht fo r Mo ntro se Ro a d to wa rd T

we r Oa ks Blvd (1.1 mi.)

K e e p le ft o nto Mo ntro se Pkwy (1.2 mi.) T a ke ra mp le ft fo r MD-355 N / Ro c kville Pike (0.7 mi.) Arrive a t MD-355 N / Ro c kville Pike o n the rig ht (0.0 mi.) Dista nc e F ro m Ho te l: 22.9 mi. / T ra ve l T ime : 34 min. Sub wa y/ Ra il $8.00 USD / T a xi $55.00 USD – One Wa y

(IAD) WASHINGT ON DUL L E S INT E RNAT IONAL AIRPORT DIRE CT IONS

De pa rt Sa a rine n Circ le to wa rd Dulle s Airpo rt Ac c e ss Rd (0.3 mi.) 68

SLIDE 74

K e e p rig ht o nto Dulle s Airpo rt Ac c e ss Rd (12.1 mi.) T a ke ra mp rig ht fo r VA-267 E to wa rd E xit 18-19 / Ric hmo nd / Ba ltimo re (1.1 mi.) At e xit 18B, ta ke ra mp rig ht fo r I-495 No rth to wa rd Ba ltimo re (7.5 mi.) K e e p le ft o nto I-270 N Spur (2.0 mi.) K e e p stra ig ht o nto I-270 N (0.9 mi.) K e e p rig ht to sta y o n I-270 N / Dwig ht D E ise nho we r Hwy / I

270 L
c al L

a ne s / Wa shing to n Na tio na l Pike (0.3 mi.) At e xit 4A, ta ke ra mp rig ht fo r Mo ntro se Ro a d to wa rd T

we r Oa ks Blvd (1.1 mi.)

K e e p le ft o nto Mo ntro se Pkwy (1.2 mi.) T a ke ra mp le ft fo r MD-355 N / Ro c kville Pike (0.7 mi.) Arrive a t MD-355 N / Ro c kville Pike o n the rig ht (0.0 mi.) Dista nc e fro m Ho te l: 27.2 mi. / T ra ve l T ime : 35 min. T a xi $60.00 USD – One Wa y

(BWI) BAL T IMORE / WASHINGT ON INT E RNAT IONAL DIRE CT IONS

De pa rt fro m Baltimo re -Wa shing to n T hurg o o d Ma rshall I nte rna tio na l Airpo rt, MD (0.5 mi.) K e e p le ft o nto I-195 W (1.9 mi.) At e xit 2B, ta ke ra mp rig ht fo r MD-295 So uth to wa rd Wa shing to n (3.0 mi.) T a ke ra mp rig ht fo r MD-100 We st to wa rd E llic o tt City (2.6 mi.) At e xit 5A-B, ta ke ra mp rig ht fo r I-95 So uth to wa rd Wa shing to n (15.8 mi.) At e xit 27, ta ke ra mp rig ht fo r I-495 We st to wa rd Silve r Spring (9.7 mi.) At e xit 34, ta ke ra mp rig ht fo r MD-355 to wa rd Ro c kville / Wisc o nsin Ave / Be the sd a (3.4 mi.) Arrive a t MD-355 N / Ro c kville Pike o n the rig ht (0.0 mi.) Dista nc e fro m Ho te l: 36.8 mi. / T ra ve l T ime : 45 min. T a xi $75.00 USD

ME T RO RAIL SYST E M

F ro m Ro nald Re a g a n Na tio na l Airpo rt o nly T a ke the Ye llo w L ine to wa rd s Ge o rg ia Ave nue / Pe two rth. Ge t o ff a t Ga lle ry Plac e / China to wn, tra nsfe r sta tio n to the Re d a nd Gre e n L ine s. T a ke the Re d L ine to wa rd s Sha d y Gro ve . E xit tra in a t the T winb ro o k Sto p . T he Hilto n is lo c a te d a c ro ss the stre e t fro m the sta tio n. 69

SLIDE 75

Genomic Medicine Meeting VIII Contact List

Anjene Addington, PhD, MPH Genomics Research Branch Health Scientist Administrator at the National Institutes of Health (NIH) Email: anjene.addington@nih.gov Phone: 301-443-6653 Warwick Anderson, AM, PhD, Univ., FAHA (int), FRPCA Human Frontier Science Program Strasbourg, France Email: wanderson@hfsp.org Phone: +33 3 88 21 51 23 Steven Benowitz, MA Associate Director of Communications, Extramural Research Program; National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) Email: steven.benowitz@nih.gov Phone: 301-451-8325 Jonathan Berg, MD, PhD Assistant Professor, Department of Genetics and Cancer Genetics Clinic at University of North Carolina, Chapel Hill Email: jsberg@med.unc.edu Phone: 919-966-7043 Adam C. Berger, Ph.D Senior Program Officer and Director of the Roundtable on Translating Genomic-Based Research for Health in the Board on Health Sciences Policy at the Institute of Medicine, Email: aberger2@nas.edu Phone: 202-334-3756 Vence L. Bonham, Jr., JD JD, Chief, Education and Community Involvement Branch; Associate Investigator; Social and Behavioral Research Branch; National Human Genome Research Institute Email: bonhamv@mail.nih.gov Phone: 301-594-3973 Erwin Bottinger, MD Director Charles R. Bronfman Institute for Personalized Medicine; Professor of Medicine and Nephrology; Professor of Pharmacology and Systems Therapeutics Email: erwin.bottinger@mssm.edu Phone: 212-241-6193 Phillip Bourne, PhD, FACMI Associate Director for Data Science (ADDS) at the National Institute of Health Email: philip.bourne@nih.gov Phone: 301-496-5787 Joy Boyer, BA Senior Program Analyst Ethical, Legal and Social Implications Research Program; National Human Genome Research Institute (NHGRI); National Institutes of Health (NIH). Email: boyerj@exchange.nih.gov Phone: 301-402-4997 Ruth Brenner, MD, MPH Eunice Kennedy Shriver National Institute

f Child Health and Human

Development; Pediatric Trauma and Critical Illness Branch; National Institute

f Health (NIH)

Email: ruth.brenner.mil@mail.mil Phone: 301-594-8668 Lawrence Brody, PhD Director, Division of Genomics and Society; National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) Email: lbrody@mail.nih.gov Phone: 301-496-7824 Carol Bult, PhD Professor and Cancer Center Deputy Director Mammalian Genetics The Jackson Laboratory for Genomic Medicine Email: carol.bult@jax.org Phone: 207-288-6324 70

SLIDE 76

Genomic Medicine Meeting VIII Contact List

Rex Chisholm, PhD Adam and Richard T. Lind Professor of Medical Genetics in the Feinberg School of Medicine and professor of Cell and Molecular Biology and Surgery Email: r-chisholm@northwestern.edu Phone: 847-491-3741 Christopher Chute, MD, DR.PH Professor of Medicine, Public Health, and Nursing. Chief Health Information Research Officer, John Hopkins Medicine Email: chute@jhu.edu Phone: 410-955-0532 Barbara Conley, MD Associate Director, Cancer Diagnosis Program Division of Cancer Treatment and Diagnosis; National Cancer Institute Email: barbara.conley@nih.gov Phone: 240-276-6505 Maurico de Castro-Pretelt, MD National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH). Email: mauricio.decastro- pretelt@nih.gov Phone: 813-253-9291 Elise Feingold, PhD Program Director, Genome Analysis, Division of Genome Sciences; National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH). Email: Elise_Feingold@nih.gov Phone: 301-496-7531 Adam Felsenfeld, PhD Program Director, Division of Genome Sciences; National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH). Email: felsenfa@exchange.nih.gov Phone: 301-496-7531 Robert Freimuth, PhD Associate Consultant, Division of Biomedical Statistics and Informatics; Assistant Professor of Medical Informatics; Health Sciences Research; Mayo Clinic College of Medicine Email: freimuth.robert@mayo.edu Phone: 507-284-0753 William Gahl, MD, PhD Clinical Director, National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH). Email: gahlw@helix.nih.gov Phone: 301-402-2739

J. Mike Gaziano, MD, PhD

Professor of Medicine, Harvard Medical School; Brigham and Women’s Hospital; Division of Aging Email: jmgaziano@partners.org Phone: 617-278-0785 Geoffrey S Ginsburg, MD, PhD Director of the Center for Applied Genomic & Precision Medicine, Duke University Health System Email: Geoffrey.ginsburg@duke.edu Phone: 919-668-6210 Jonathan M. Gitlin, PhD Science Policy Analyst; Policy and Program Analysis Branch; National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH). Email: gitlinjm@mail.nih.gov Phone: 301-594-6593 Katrina Goddard, PhD Director, Knowledge Synthesis Team, Co-Chair of the Action Ability Work Group; Kaiser Permanente Research Email: Katrina.AB.Goddard@kpchr.org Phone: 503-528-3920 71

SLIDE 77

Genomic Medicine Meeting VIII Contact List

Eric D. Green, M.D., Ph.D Director of the National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH Email: egreen@nhgri.nih.gov Phone: 301-402-0911 Robert Green, MD, PhD Associate Physician, Brigham and Women’s Hospital; Associate Professor

f Medicine, Harvard Medical School

Email: rcgreen@genetics.med.harvard.edu Phone: 617-525-4703 Katrina Gwinn, MD Program Director, Extramural Research Program, National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (NIH) Email: gwinnk@ninds.nih.gov Phone: 301-496-5745 Craig Hanis, PhD Professor, School of Public Health, Department of Epidemiology, Human Genetics and Environmental Sciences; the University of Texas Health Science Center at Houston Email: Craig.L.Hanis@uth.tmc.edu Phone: 713-500-9807 Lucia Hindorff, PhD, MPH Program director in the Division of Genomic Medicine at NHGRI, Project scientist for the Clinical Sequencing Exploratory Research (CSER) Email: hindorffl@mail.nih.gov Phone: 301-402-5759 Carolyn Hutter, PhD Program Director, Division of Genomic Medicine; National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) Email: huttercm@mail.nih.gov Phone: 301-451-4735 Howard Jacob, PhD Professor, Physiology and Human Molecular Genetics; Director, Human and Molecular Genetics Center, Warren

P. Knowles Chair of Genetics, Medical

College of Wisconsin Email: jacob@mcw.edu Phone: 414-456-4887 Cashell Jaquish, PhD Program Director, National Heart, Lung, and Blood Institute National Institutes of Health Email: cj68r@nih.gov Phone: 301-435-0447 Gail Jarvik, MD, PhD Head and Professor, Division of Medical Genetics; The Arno G. Motulsky Endowed Chair in Medicine; Joint Professor of Medicine and Genome Sciences; Adjunct Professor of Epidemiology; University of Washington Email: pair@u.washington.edu Phone: 206-221-3974 Jean Jenkins, PhD, RN, FAAN Clinical Advisor, Genomic Healthcare Branch; National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) Email: jean.jenkins@nih.gov Phone: 301-547-1897 Steve Joffe, MD, PhD Vice Chair of Medical Ethics; Emanuel and Robert Hart Associate Professor University of Pennsylvania; Department

f Medical Ethics & Health Policy

Email: joffes@upenn.edu Phone: 215-898-7136 72

SLIDE 78

Genomic Medicine Meeting VIII Contact List

Julie A. Johnson, Pharm.D., BCPS, FCCP, FAHA Dean of the University of Florida College

f Pharmacy and Distinguished

Professor of Pharmacy (Department of Pharmacotherapy and Translational Research) and Medicine; (Department

f Medicine, Division of Cardiovascular

Medicine) in the Colleges of Pharmacy and Medicine Email: johnson@cop.ufl.edu Phone: 352-273-6312 Heather Junkins, MS Program Director; National Human Genome Research Institute National Institutes of Health Email: junkinsh@mail.nih.gov Phone: 301-402-0343 Stephen Kingsmore, MB, ChB, BAO, DSc, FRCPath Executive Director, Pediatric Genomic Medicine at Children’s Mercy Hospital in Kansas City Email: sfkingsmore@cmh.edu Phone: 816-234-3059 Jennie Larkin, PhD Health Scientist Administrator with the Bioengineering and Genomic Applications Scientific Review Group in the Division of Heart and Vascular Diseases at the National Heart Lung and Blood Institute (NHLBI) at the National Institutes of Health (NIH) Email: larkinJ2@nhlbi.nih.gov Phone: 301-435-0513 William Lawrence, MD, MS Senior Program Officer, Science Communication and Dissemination Research Department at Patient- Centered Outcomes Research Institute (PCORI) Email: wlawrence@pcori.org Phone: 202-827-7700 Rongling Li, MD, PhD, MPH Epidemiologist for the Division of Genomic Medicine; National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) Email: lir2@mail.nih.gov Phone: 301-594-6524 Nicole Lockhart, PhD Health Sciences Administrator, Division

f Genomics and Society, National

Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) Email: lockhani@mail.nih.gov Phone: 301-435-5697 Rochelle Long, PhD Chief, Pharmacological and Physiological Sciences Branch; National Institute of General Medical Sciences (NIGMS) at the National Institute of Health (NIH) Email: longr@nigms.nih.gov Phone: 301-594-3827 Ebony Madden, PhD Epidemiologist, Division of Genomic Medicine; National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) Email: ebony.madden@nih.gov Phone: 301-503-5620 Teri Manolio, M.D., Ph.D Director Division of Genomic Medicine, National Human Genome Research Institute (NHGRI) Email: manolio@nih.gov Phone: 301-402-2915 Jean McEwen, JD, PhD Program Director, National Human Genome Research Institute National Institutes of Health Email: mcewenj@mail.nih.gov Phone: 301-402-4997

SLIDE 79

Genomic Medicine Meeting VIII Contact List

Howard McLeod, PharmD Medical Director of the DeBartolo Family Personalized Medicine Institute at the Moffitt Cancer Center Email: howard.mcleod@moffitt.org Phone: 813-745-4673 Alexa McCray, PhD Associate Professor of Medicine Harvard Medical School and the Department of Medicine, Beth Israel Deaconess Medical Center; Co- Director, Center for Biomedical Informatics; Associate Director, Francis

A. Count way Library of Medicine

Email: alexa_mccray@hms.harvard.edu Phone: 617-432-8326 Pierre Meulien, Ph.D President and CEO of Genome Canada, Canada Email: pmeulien@genomecanada.ca Phone: 613-751-4460 Annie Niehaus ClinGen Analyst, National Human Genome Research Institute (NHGRI) Email: annie.niehaus@nih.gov Dina Paltoo, PhD, MPH Director, Genetics, Health and Society Program; Office of Science Policy, Office of the Director at the National Institutes of Health (NIH) Email: paltood@od.nih.gov Mike Pazin, PhD Program Director, Functional Genomics, Division of Genome Sciences, National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) Email: pazinm@mail.nih.gov Phone: 301-496-7531 Sharon Plon, MD, PhD Professor of Pediatrics-Oncology; Molecular and Human Genetics; Program in Integrative Molecular and Biomedical Sciences, Human Genome Sequencing Center; MSTP Program Director – Baylor College of Medicine; Director of Neurofibromatosis Clinic; Director, Cancer Genetics Clinical and Research Program – Texas Children’s Hospital Email: splon@bcm.edu Phone: 832-824-4251 Cynthia Powell, MD, MS Associate Professor, Department of Genetics and Pediatrics, University of North Carolina, Chapel Hill Email: powellcm@med.unc.edu Phone: 919-966-4202 Erin Ramos, PhD, MPH Epidemiologist, Office of Population Genomics National Human Genome Research Institute National Institutes of Health Email: ramoser@mail.nih.gov Phone: 301-451-3706 Gurvaneet Randhawa, MD, MPH Medical Officer Senior Advisor on Clinical Genomics & Personalized Medicine Center for Evidence and Practice Improvement (CEPI); Agency for Healthcare Research and Quality (AHRQ) US Department of Health & Human Services Email: Gurvaneet.Randhawa@ahrq.hhs.gov Phone: 301-427-1619 74

SLIDE 80

Genomic Medicine Meeting VIII Contact List

Heidi L. Rehm, PhD, FACMG Director of the Laboratory for Molecular Medicine at the Partners Healthcare Center for Personalized Genetic Medicine and Assistant Professor of Pathology at Harvard Medical School Email: hrehm@partners.org Phone: 617-954-9392 Mary V. Relling, Pharm.D Member and Chair, Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital Email: mary.relling@stjude.org Phone: 901-595-3300 Laura Lyman Rodriguez, Ph.D Director of the Division of Policy, Communications, and Education, National Human Genome Research Institute (NHGRI) Email: laura.rodriguez@nih.gov Phone: 301-594-3973 Dan Roden, MD Principal investigator for the Vanderbilt sites of the National Institutes of Health’s Pharmacogenomics Research Network (PGRN) and the NHGRI’s Electronic Medical Records and Genomics (eMERGE) Network Email: dan.roden@vanderbilt.edu Phone: 615-322-0067 Wendy Rubinstein, MD, PhD Director, National Institute of Health (NIH) Genetic Testing Registry and Senior Scientist Email: rubinstw@ncbi.nlm.nih.gov Jeffery A. Schloss, PhD Director, Division of Genome Sciences and Program Director for Technology Development Coordination in the Extramural Research Program at the NHGRI Email: schlossj@exchange.nih.gov Phone: 301-594-3973 Derek Scholes, PhD Chief, Policy and Program Analysis Branch; National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) Email: derek.scholes@nih.gov Phone: 301-435-1747 Sheri Schully, PhD Team Lead; Knowledge Integration Team; Division of Cancer Control and Population Sciences, Office of the Associate Director National Cancer Institute, NIH Email: schullys@mail.nih.gov Phone: 240-276-6936 Heidi Sofia, PhD, MPH Program Director, Computational Biology Division of Genomic Medicine National Human Genome Research Institute National Institutes of Health Email: sofiahj@mail.nih.gov Phone: 301-496-7531 Jeff Struewing, MD Epidemiologist, Office of Population Genomics National Human Genome Research Institute National Institutes of Health Email: struewij@mail.nih.gov Phone: 301-594-3757 Jennifer Troyer, PhD Program Director, Human Heredity and Health in Africa, National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) Email: troyerj@mail.nih.gov Phone: 301-402-2852 Santa Tumminia, PhD Bioinformatics, Genetics Neuroscience; National Eye Institute Email: tumminias@nei.nih.gov Phone: 301-496-2234 75

SLIDE 81

Genomic Medicine Meeting VIII Contact List

Tiina Urv, PhD Eunice Kennedy Shriver National Institute

f Child Health and Human

Development Program Director for the Intellectual and Developmental Disabilities Branch Email: urvtiin@mail.nih.gov Phone: 301-405-7015 Simona Volpi, PhD Program Director, Genotype-Tissue Expression Project (GTEx), Division of Genome Sciences; National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) Email: volpis@mail.nih.gov Phone: 301-443-6453 Lu Wang, PhD Program Director, Genome Sequencing Program National Human Genome Research Institute National Institutes of Health Email: wanglu@mail.nih.gov Phone: 301-594-7303 Jon White, MD Director, Health Informatics Technology (Health IT) at the Agency for Healthcare Research and Quality (AHRQ) Email: Jonathan.White@ahrq.hhs.gov Louise Wideroff, PhD, MSPH National Institutes of Health Science Officer for the H3 Africa Biorepository

Program. National Eye Institute

Email: widerofl@nei.nih.gov Phone: 301-496-7531 Bob Wildin, MD Chief, Genomic Healthcare Branch, National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) Email: bob.wildin@nih.gov Phone: 301-496-0844 Ken Wiley, Jr., PhD Program Director, Division of Genomic Medicine; National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) Email: ken.wiley@nih.gov Phone: 301-435-5540 Janet Williams, LGC, MS Director, Research Genetic Counselors Genomic Medicine Institute Geisinger Health System Email: jlwilliams3@geisinger.edu Phone: 570-214-7942 Marc S. Williams, MD, FAAP, FACMG Director, Genomic Medicine Institute Geisinger Health System Email: mswilliams1@geisinger.edu Phone: 570-271-6692 Anastasia L. Wise, PhD Epidemiologist in the Division of Genomic Medicine at the National Human Genome Research Institute (NHGRI) Email: Anastasia.wise@nih.gov Phone: 301- 443-0585 Catherine Witkop, MD, MPH Preventive Medicine Physician and the Director of the Trainee Health Program at the US Air Force Academy Email: catherine.t.witkop.mil@mail.mi Phone: 719-333-6239 76

SLIDE 82

Ge nomic Me dic ine VIII Suppor t T e am June 8-9, 2015 Be the sda, MD

R ita L . Cha mbe r s, BS - is the

Se nio r Pro g ra m Co o rdina to r

f the Ce nte r fo r Applie d

Ge no mic & Pre c isio n Me dic ine ; a t Duke Unive rsity fo r o ve r the pa st e ig ht ye a rs. She is a lso the suppo rt te a m fo r the NHGRI Ge no mic Me dic ine Me e ting s. Ms. Cha mb e rs ha s o ve r 20 ye a rs’ c o mb ine d e xpe rie nc e in the a dministra tio n,

rg a niza tio n, a nd pro mo ting me e ting s

a nd a c tivitie s fo r nume ro us o rg a niza tio ns a nd c o rpo ra tio ns inc luding Duke Unive rsity, L a b Co rp, a nd Se g ro -Co lo nia l Ab ra sive s. She ha s b e e n a c kno wle dg e d fo r he r e ffo rts with the o rg a niza tio n o f “Ge no mic and Pe rso nalize d Me dic ine ”, Se c o nd E ditio n, V1-2 Ha rdc o ve r, Ginsb urg GS a nd Willa rd HW, 2012. Org a nize d a nd E dito ria l E ffo rts in ke e ping the pro je c t o n ta sk fo r c o mple tio n. She wa s a lso a wa rde d the Pre side ntia l Me rito rio us Awa rd fo r he r re c o g nitio n o f o utsta nding se rvic e s to Duke Unive rsity. Ms. Cha mb e rs ha s a b a c kg ro und in Busine ss Administra tio n with a c o nc e ntra tio n in Ma na g e me nt a nd Org a niza tio na l De ve lo pme nt a nd c urre ntly studying fo r he r Dua l Ma ste r’ s De g re e s in Busine ss Administra tio n a nd Sc ie nc e in L e a de rship a t Pfe iffe r Unive rsity in Cha rlo tte , NC.

Ja c que line Og dis, BS - is the

Sc ie ntific Pro g ra m Ana lyst fo r the Na tio na l I nstitute s

He a lth; Divisio n o f Ge no mic Me dic ine

E lia n Silve r ma n, BA – the

Sc ie ntific Pro g ra m Ana lyst fo r the Na tio na l I nstitute s o f He a lth; T he Ca nc e r Atla s Ge no me Pro je c t (T CGA), (CSE R), a nd the Ge no mic Me dic ine Wo rking Gro up

T e jinde r R a khr a- Bur r is, MA - is

the Pro g ra m L e a de r o f the Duke Ce nte r fo r Pe rso na lize d a nd Pre c isio n Me dic ine (CPPM) with the Ce nte r fo r Applie d Ge no mic & Pre c isio n Me dic ine ; a t Duke Unive rsity a nd ha s o ve r 10 ye a rs o f e xpe rie nc e in a dministra tio n a nd pro g ra m ma na g e me nt o f sc ie ntific re se a rc h in hig he r e duc a tio n. In a dditio n to pa rtic ipa ting in the stra te g ic a nd a dministra tive / o pe ra tio na l le a de rship o f the CPPM, she a lso is the pro g ra m ma na g e r fo r the NHGRI

funde d g e no mic

de mo nstra tio n pro je c t e ntitle d “Imple me nta tio n, Ado ptio n, a nd Utility o f F a mily Histo ry in Dive rse Se tting s” a nd

ve rse e s the ma na g e me nt o f two Unite d

Sta te s Air F

rc e c o o pe ra tive a g re e me nts.

Prio r to jo ining Duke , she wa s the Asso c ia te Dire c to r fo r Re se a rc h with the Unive rsity o f No rth Ca ro lina Institute fo r Pha rma c o g e no mic s a nd I ndividua lize d T he ra py, a nd pre vio usly ma na g e d a CDC- funde d pub lic he a lth g e ne tic s pro g ra m a t the UNC Sc ho o l o f Pub lic He a lth, a nd a n NIE HS-funde d c o o pe ra tive a g re e me nt into the fe a sib ility

e sta b lishing a na tio na l twin re g istry fo r g e ne tic a nd e nviro nme nta l a sso c ia tio n studie s. Ms. Ra khra -Burris ha s a b a c kg ro und in b usine ss a dministra tio n a nd a Ma ste r’ s De g re e in Mo le c ula r Ge ne tic s fro m Wa shing to n Unive rsity in St. L

uis.

Alva r

nc ina s

Visua l Pro fe ssio na l a t the Na tio na l Huma n Ge no me Re se a rc h I nstitute .

Kia r a Pa lme r , BA – Pub lic Affa irs

Spe c ia list & Vide o Pro duc e r a t Na tio na l I nstitute s o f He a lth’ s (NIH); a t the Na tio na l Huma n Ge no me Re se a rc h I nstitute .