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Crowdsourcing pharmacogenomic data analysis: PGRN-Sage RA Responder Challenge PGRN Spring Meeting April 30, 2013 HARVARD MEDICAL SCHOOL
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Crowdsourcing pharmacogenomic data analysis: PGRN-Sage RA Responder Challenge

Feb 24, 2016

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Crowdsourcing pharmacogenomic data analysis: PGRN-Sage RA Responder Challenge. PGRN Spring Meeting April 30, 2013. HARVARD MEDICAL SCHOOL. Predicting response in RA. N=2,700 RA patients. How our data are silo’d. GWAS (n=2,700). How our data are silo’d. GWAS (n=2,700). - PowerPoint PPT Presentation
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Page 1: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

Crowdsourcing pharmacogenomic data analysis: PGRN-Sage RA Responder Challenge

PGRN Spring Meeting

April 30, 2013

HARVARDMEDICAL SCHOOL

Page 2: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge
Page 3: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

Predicting response in RA

N=2,700 RA patients

Page 4: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

GWAS(n=2,700)

How our data are silo’d

Page 5: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

GWAS(n=2,700)

How our data are silo’d

Page 6: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

The power of the crowd…

Page 7: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

Crowdsourcing is not a new idea…

Page 8: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

Crowdsourcing today is widely used

Page 9: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

• Engage large group of participants– Beyond our immediate collaborators

• Open dialogue on methods and results– Rapid-learning, with insights in real-time

• Facilitate peer-review– Challenge-assisted vs traditional peer-

review

Benefits of crowdsourcing

Plenge et al Nature Genetics 2013

Page 10: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

How can we effectively use crowdsourcing for

PGx traits?

Page 11: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

• Define a discrete biological questions– Polygenic predictor of response to anti-TNF

therapy in rheumatoid arthritis• Assemble unique datasets

– Discovery GWAS (n=2,700 RA patients)– Validation GWAS (n=1,100 RA patients)***– Additional genomic data (RNA-seq, etc)

• Partner with group to host Challenge– Sage-DREAM

• Assemble teams to compete– Any group with IRB approval!

RA Responder Challenge

*** RIKEN application pending

Page 12: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

RA Responder ChallengeDiscovery (phase I)

GWAS of treatment response in RA

(n≈2,700 patients)

Genomic data(e.g., expression

profiling)

Polygenic SNPpredictor of response

What is the best SNP-based genetic model to predict response to anti-

TNF therapy in RA?Polygenic modeling projectEli StahlSarah PendergrassMarylyn RitchieJing Cui

Page 13: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

RA Responder ChallengeDiscovery (phase I)

GWAS of treatment response in RA

(n≈2,700 patients)

Genomic data(e.g., expression

profiling)

Polygenic SNPpredictor of response

*** An outcome of the PGRN polygenic modeling network-wide project

Page 14: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

RA Responder ChallengeDiscovery (phase I)

GWAS of treatment response in RA

(n≈2,700 patients)

Genomic data(e.g., expression

profiling)

Polygenic SNPpredictor of

response

Refine model

Open Collaboration

Peer insights1)2)

etc.

synapse

Build models as a community,

sharing insights in real-time

Sage BionetworksLara MangraviteJonathan DerryStephen Friend

Page 15: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

RA Responder ChallengeDiscovery (phase I)

Validation (phase II)GWAS of treatment response in RA

(n≈2,700 patients)

Genomic data(e.g., expression

profiling)

Polygenic SNPpredictor of

response

Refine model

Open Collaboration

Peer insights1)2)

etc.

Submit models GWAS of treatment

response in RA(n≈1,100 patients)

Score models

synapse

Test models in an independent dataset

(CORRONA)

CORRONAJeff GreenbergDimitrios PappasJoel Kremer

Page 16: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

RA Responder ChallengeDiscovery (phase I)

Validation (phase II)GWAS of treatment response in RA

(n≈2,700 patients)

Genomic data(e.g., expression

profiling)

Polygenic SNPpredictor of

response

Refine model

Open Collaboration

Peer insights1)2)

etc.

Challenge-assisted peer review

Submit models GWAS of treatment

response in RA(n≈1,100 patients)

Score models

Publication peer review

synapse

Peer-review

responses

PublicationPublish with

Nature Genetics

Page 17: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge
Page 18: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

• Scientific– What is the power to detect polygenic signal?– How much will genomic datasets add?– Is a SNP-based approach the best?

• Social– Will groups collaborate or compete?– Is the Synapse platform sufficient to

communicate among diverse groups?• Practical

– How will we manage data access?

Unresolved questions of our crowdsourcing approach

Page 19: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

• Industry sponsorship– Several companies have promised support

to host the Challenge– Initial conversations to generate more data

• Foundation sponorship– Arthritis Foundation has supported the

Challenge, given next-gen approach and “citizen-scientist” emphasis

• Sharing among colleagues – no issues sharing data…actually more!

Initial surprises from putting the Challenge together

Page 20: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

• RNA-predictors of response

• Internet registry “citizen-scientist” clinical trial

• NIH academic-industry “target validation consortium”– “disease deconstruction”

This is meant to be the first step

Page 21: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

Sage-DREAM collaboration

• Breast Cancer Challenge– Published in Science Translational Medicine

• Glioblastoma Challenge

• Other Challenges planned for 2013– See sagebase.org for list of Challeges

Page 22: Crowdsourcing  pharmacogenomic  data analysis:  PGRN-Sage RA Responder Challenge

Is crowdsourcing attractive to other PGRN

investigators?