BRCA Challenge GA4GH Demonstraon project in collaboraon with ENIGMA Iniated 2014 by Sir John Burn, Newcastle University & Stephen Chanock, Naonal Cancer Instute Current “Driver” team: Amanda Spurdle – QIMR Berghofer Medical Research Instute, Brisbane Gunnar Raetsch - ETH Zurich David Goldgar, Sean Tavgian - Huntsman Cancer Instute, University of Utah, Salt Lake City Melissa Cline, Benedict Paten - University of California, Santa Cruz Rachel Liao – Broad Instute, Cambridge, Massachuses

1 genomicsandhealth.org BRCA Challenge – Instuons: Steering Commiee

Internaonal representaon

John Burn, Newcastle University, Newcastle upon Tyne, UK Robert Nussbaum, University of California San Francisco, USA Stephen Chanock, National Cancer Institute, Rockville, USA Kenneth Offit, Memorial Sloan Kettering Cancer Center, New York, USA Antonis Antoniou, University of Cambridge, Cambridge, UK Sharon Plon, Baylor College of Medicine, Houston, USA Larry Brody, National Human Genome Research Institute, Bethesda, USA Gunnar Rätsch, ETH Zurich, Zurich, Switzerland Robert Cook-Deegan, Duke University, Durham, USA Nazneen Rahman, Institute of Cancer Research, London, UK Fergus Couch, Mayo Clinic, Rochester, USA Heidi Rehm, Harvard Medical School, Boston, USA Johan den Dunnen, Leiden University Medical Center, Leiden, Netherlands Mark Robson, Memorial Sloan Kettering Cancer Center, NY City, USA Susan Domchek, University of Pennsylvania, Philadelphia, USA Wendy Rubinstein, National Institute of Health, Bethesda, USA Douglas Easton, University of Cambridge, Cambridge, UK Amanda Spurdle, QIMR Berghofer Medical Research Institute, BNE, Australia William Foulkes, McGill University, Montreal, Canada Dominique Stoppa-Lyonnet, Curie Institute, Paris, France Judy Garber, Dana-Farber Cancer Institute, Boston, USA Sean Tavtigian, Hunstman Cancer Institute, Salt Lake City, USA David Goldgar, Huntsman Cancer Institute, Salt Lake City, USA David Haussler, UC Santa Cruz Genomics Institute, Santa Cruz, USA Kazuto Kato, Osaka University, Osaka, Japan Bartha Knoppers, McGill University, Montreal, Canada Delyth Jane Morgan, Breast Cancer Now, Cancer Research UK

2 genomicsandhealth.org BRCA Challenge – Instuons across the globe

John Burn, Newcastle University, Newcastle upon Tyne, UK Stephen Chanock, Naonal Cancer Instute, Rockville, USA Antonis Antoniou, University of Cambridge, Cambridge, UK Larry Brody, Naonal Human Genome Research Instute, Bethesda, USA Robert Cook-Deegan, Duke University, Durham, USA Fergus Couch, Mayo Clinic, Rochester, USA Johan den Dunnen, Leiden University Medical Center, Leiden, Netherlands Susan Domchek, University of Pennsylvania, Philadelphia, USA Douglas Easton, University of Cambridge, Cambridge, UK William Foulkes, McGill University, Montreal, Canada Judy Garber, Dana-Farber Cancer Instute, Boston, USA David Goldgar, Huntsman Cancer Instute, Salt Lake City, USA Kazuto Kato, Osaka University, Osaka, Japan Delyth Jane Morgan, Baroness Morgan of Drefelin, Breast Cancer Now, Cancer Research UK Robert Nussbaum, University of California San Francisco, San Francisco, USA Kenneth Offit, Memorial Sloan Keering Cancer Center, New York, USA Sharon Plon, Baylor College of Medicine, Houston, USA Gunnar Rätsch, ETH Zurich, Zurich, Switzerland Nazneen Rahman, Instute of Cancer Research, London, UK Heidi Rehm, Harvard Medical School, Boston, USA Mark Robson, Memorial Sloan Keering Cancer Center, New York City, USA Wendy Rubinstein, Naonal Instute of Health, Bethesda, USA Amanda Spurdle, QIMR Berghofer Medical Research Instute, Herston, Australia Dominique Stoppa-Lyonnet, Curie Instute, Paris, France Sean Tavgian, Hunstman Cancer Instute, Salt Lake City, USA David Haussler, UC Santa Cruz Genomics Instute, Santa Cruz, USA Bartha Knoppers, McGill University, Montreal, Canada

3 genomicsandhealth.org BRCA Challenge – Project Overview

● Mission: Improve care of paents at risk of breast and ovarian cancer using global data sharing and collaboraon in the analysis of BRCA1 and BRCA2 1.Share BRCA1 and BRCA2 variants publically via a web portal 2.Address social, ethical, legal challenges to global data sharing 3.Create a GA4GH model for all disease genes

● Clinical Focus: Germline variant classificaon

● Major milestones: – BRCA Exchange - >17,900 variants, mulple sites – 1/3 expert-classified with supporng raonale – coming soon… mobile app with alert funcon

4 genomicsandhealth.org BRCA Exchange Website

Gunnar Raetsch, Melissa Cline, Benedict Paten & others

Features:

• Flexible searching

• Drill down to extra info - Tiled format

• Versioning... - Variant level - Dataset level

5 genomicsandhealth.org BRCA Challenge Mobile App

Gunnar Raetsch & Faisal Alquaddoomi

Features:

● Simplified presentaon

● Follow a variant funconality (in tesng phase)

6 genomicsandhealth.org BRCA Challenge – Goals & Previous Engagement

● Goals: * Variant level data – classificaon, raonale, other * Individual level data – clinical info, differing access * Algorithms to automate collecon/classificaon

● Previous Engagement with GA4GH: * Ethics & regulatory: - FDA guidance (NGS tesng & public variant databases) - Ethics WG chairs - database liability pub (GIM 19: 839) * Data WG: Adopted the GA4GH API - To allow others to access BRCA-Exchange data * ….. currently integrang with the Beacon network

7 genomicsandhealth.org BRCA Challenge – Standards needed for Data sharing

● Genomic Knowledge & Clinical/Phenotype data ● genomic nomenclature “translaon” ● associated clinical informaon/phenotype - including paent ascertainment ● genec & clinical data provenance/quality ● Data use & Researcher IDs - view & re-use of data ● for clinical/research purpose ● open access vs controlled (how much/who) ● Cloud - interoperability ● opmising workflow, GA4GH approval stamp ● Discovery - controlling for overlapping data

8 genomicsandhealth.org BRCA Challenge – What we can offer to GA4GH?

● Feedback of BRCA Challenge developments ● Algorithms for automated variant priorizaon/classificaon ● Field tesng of standards on variant representaon and clinical data ● Mobile app for variant view and classificaon updates

9 genomicsandhealth.org BRCA Challenge

Q&A

Gunnar, Benedict & Melissa to chime in!

10 genomicsandhealth.org