Data Sharing: Highlights from NCI Experience and Cancer Moonshot Task Force
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Presentation at 2018 Biomedical Transparency Summit hosted by the Center for Biomedical Research Transparency.
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Data Sharing: Highlights from NCI Experience and Cancer Moonshot Task Force
- 1. Biomedical Transparency Summit Hyatt Regency, Bethesda MD January 26th, 2018 Jerry S.H. Lee, Ph.D. Deputy Director, Center for Strategic Scientific Initiatives Office of the Director, National Cancer Institute, National Institutes of Health Data Sharing: Highlights from NCI Experience and Cancer Moonshot Task Force
- 2. Primary tumor (Localized) Metastasis (Distant) “…>90% of deaths are caused by disseminated disease or metastasis…” 5 year Relative Survival Rates (2016 report of 2005-2011 data) Tumor, Cancer, and Metastasis: Length-scale and Time-scale Matter Siegel et. al. CA Cancer J Clin, Jan/Feb 2016
- 3. 06 2005 2018 Joined NCI Center for Strategic Scientific Initiatives (CSSI) 08 Official “Other Duties As Assigned” 09 Transitioned to Deputy Director, CSSI 10 16 Served as Deputy Director for Cancer Research and Technology WH Cancer Moonshot Task Force 4/14/16 – 1/11/17 10/17/16 PhD in Chemical and Biomolecular Engineering Nuclear and Cellular Mechanics: Implications for Laminopathies and Cancer
- 4. “What is Water?”: Measurements Insights Color (clear, yellow, brown) Taste (none, metallic, awful) LOTS of Quantitative “Data” Qualitative Descriptions Phase (liquid, gas, solid) Phase change (boil, melt, freeze) Measurements Taken But also LOTS of disagreements… Boiling point = 92oC Boiling point = 100oC
- 5. “What is Water?”: Standards and Sharing of Data New Insights and Understanding 2400m 0m New Parameter “Pressure” LOTS of Quantitative and Reproducible Data (Steam Table) New Understanding • Phase boundaries • V/L equilibrium • Triple Point (Phase Diagram) • Define samples and protocols • Share collected data Boiling point = 92oC Boiling point = 100oC
- 7. NCI Center for Strategic Scientific Initiatives (CSSI): 2003 Present Dates indicate approval(s) by NCI Board of Scientific Advisors; *Program moved to NCI Division of Cancer Biology “…to create and uniquely implement exploratory programs focused on the development and integration of advanced technologies, trans-disciplinary approaches, infrastructures, and standards, to accelerate the creation and broad deployment of data, knowledge, and tools to empower the entire cancer research continuum in better understanding and leveraging knowledge of the cancer biology space for patient benefit…” Mission 2003, 2007, 2011, 2013, 2014, 2017 2004, 2008, 2014 2005, 2010, 2015 2005, 2008 2010 2008, 2013* 2011, 2014 Deputy Director Jerry S.H. Lee, PhD Director Douglas R. Lowy, MD
- 8. • Accelerate progress in cancer, including prevention & screening • From cutting edge basic research to wider uptake of standard of care • Encourage greater cooperation and collaboration • Within and between academia, government, and private sector • Enhance data sharing Goals of the Cancer Moonshot Initiative: (From Presidential Memo 2016) Courtesy of Dinah Singer (http://deainfo.nci.nih.gov/advisory/bsa/0316/0905Singer.pdf)
- 9. Make a decade’s worth of progress in cancer prevention, diagnosis, treatment, and care – ultimately to end cancer as we know it.
- 10. TCGA 2004 MATCH 2016 Defining mechanisms, targets, and lead molecules New methods of diagnosis, treatment, and prevention Delivery of recommended and timely care to the right patient True Benefit to society Controlled studies leading to effective care MPACT LungMAP ALCHEMIST 2004 Translational from basic science to human studies Translational of new interventions into the clinic and health decision making
- 11. (12,000+ patient tumors and increasing) 2006-2015: A Decade of Illuminating the Underlying Causes of Primary Untreated Tumors Primary tumor (Localized)
- 12. “…to conduct this mini–cancer-genome project, a 29-person team, sequenced…11 breast cancer samples and 11 colon cancer samples…then winnowed out more than 99% of the mutations by removing errors…and changes that didn’t alter a protein. …this yielded a total of 189 “candidate” cancer genes. Although some are familiar…most had never been found mutated in cancer before. The results…are a ‘treasure trove’… …the relatively small number of new genes common to the tumors reinforces concerns about [NIH] The Cancer Genome Atlas… …despite such doubts, the atlas project gets under way next week. NIH will announce the three cancers to be studied in the pilot phase…the project is on an extremely aggressive timeline…”
- 13. glioblastoma multiforme (brain) squamous carcinoma (lung) serous cystadenocarcinoma (ovarian) • Clinical diagnosis • Treatment history • Histologic diagnosis • Pathologic status • Tissue anatomic site • Surgical history • Gene expression • Chromosomal copy number • Loss of heterozygosity • Methylation patterns • miRNA expression • DNA sequence Biospecimen Core Resource with more than 13 Tissue Source Sites 7 Cancer Genomic Characterization Centers 3 Genome Sequencing Centers Data Coordinating Center Three Cancers- Pilot Multiple data types
- 14. 1st Reference Released in 2008: GBM Mid- 2008 • Reference cancer genome for GBM • Unanticipated Scientific Discoveries • Hypothesis on a possible resistance mechanism to temozolomide (TMZ) 2009 • Gene expression-based classification of GBM • Response to aggressive therapy differs by subtype- exclude non-responders 2010 • Identification of new subset of GBM • Occurs in younger patients • Evidence of better prediction of outcomes
- 16. #ofpatienttumorsamples ARRA $ Rapid Acceleration from Stimulus Funding (2009-2011) 2006 2007 2008 2009 2010 2011 Patient Samples Collected (Reality) Patient Samples Collected (Projected) Patient Samples Collected (No ARRA $)
- 17. Source: UCSC Cancer Genomic Heatmaps (CopyNumber GISTIC2) [https://genome-cancer.ucsc.edu/] Compiled by Jerry S.H. Lee, PhD, March 2013 Lung squamous: Lung adeno: Stomach adeno: Breast carc: Ovarian serous: Kidney clear cell carc: Prostate adeno: Colon/rectum adeno: Head & neck: Glioblastoma: 343 356 237 866 559 493 171 575 306 563 Total: 5,979 Brain lower grade glioma: 180 Thyroid carc: 401 Uterine corpus end. carc: 492 Liver hep. carc: 97 Kidney pap. cell carc: 103 Bladder carc: 135 Cervical carc: 102
- 18. August 2015
- 19. 1911/16/2017 NCI-MATCH Central Screening Summary • Overall match rate: 18% − Patients with a tumor gene abnormality that matched to one of the 30 treatment arms (992/5560 with testing completed) • Enrollment rate: 69% − Patients with a treatment assignment who enrolled (689/992) 11/16/2017 6,397 patients registered 5,962 samples (93% seq success rate)
- 20. Source: UCSC Cancer Genomic Heatmaps (CopyNumber GISTIC2) [https://genome-cancer.ucsc.edu/] Compiled by Jerry S.H. Lee, PhD, March 2013 Lung squamous: Lung adeno: Stomach adeno: Breast carc: Ovarian serous: Kidney clear cell carc: Prostate adeno: Colon/rectum adeno: Head & neck: Glioblastoma: 343 356 237 866 559 493 171 575 306 563 Total: 5,979 Brain lower grade glioma: 180 Thyroid carc: 401 Uterine corpus end. carc: 492 Liver hep. carc: 97 Kidney pap. cell carc: 103 Bladder carc: 135 Cervical carc: 102 2011
- 21. DNA RNA Protein Central Dogma of Biology
- 22. Re-writing Central Dogma On average across 375 tumor samples, ONLY 33% of DNA/RNA predicted cancer protein abundance Zhang, B. et. al. Proteogenomic characterization of human colon and rectal cancer. Nature. 2014 Jul 20
- 23. TCGA/CPTAC Ovarian Cancer Patient in TCIA http://cancerimagingarchive.net
- 24. Overarching Structure of CPTAC 3.0 (December 2015) A. Proteome Characterization Centers additional cancer types where questions remain on their proteogenomic complexity B. Proteogenomic Translational Research Centers apply proteogenomic assays in NCI-sponsored clinical trials C. Proteogenomic Data Analysis Centers develop innovative tools that process and integrate data across the entire proteome Data, assays and resources - community resources newtreatment-naïve cancertypes 5-6 Warren Kibbe, PhD Acting Deputy Director, National Cancer Institute Director, Center for Bioinformatics & Information Technology Henry Rodriguez, PhD, MBA Director, Office of Clinical Cancer Proteomics Research Center for Strategic Scientific Initiatives Jeff Abrams, MD Acting Director, Clinical Research Division of Cancer Treatment and Diagnosis
- 27. Catalyze New Scientific Breakthroughs Unleash the Power of Data Accelerate Bringing New Therapies to Patients Strengthen Prevention and Diagnosis Improve Patient Access and Care STRATEGIC GOALS IMPLEMENTATION PATH FEDERAL PRIVATE/ NON-PROFIT PUBLIC-PRIVATE COLLABORATION 2/1/2016 10/17/2016
- 28. Cancer Moonshot Data & Technology Team Co-Chairs: Dimitri Kusnezov (DOE), DJ Patil (OSTP), and Jerry Lee (OVP) Members: • John Scott (DoD) • Craig Shriver (DoD) • Cheryll Thomas (CDC) • Frances Babcock (CDC) • Teeb Al-Samarrai (DOE) • Sean Khozin (FDA) • Alexandra Pelletier (PIF) • Maya Mechenbier (OMB) • Henry Rodriguez (NCI) • Karen Cone (NSF) • Michael Kelley (VA) • Louis Fiore (VA) • Warren Kibbe (NCI) • Betsy Hsu (NCI) • Niall Brennan (CMS) • Thomas Beach (USPTO) • Claudia Williams (OSTP) • Vikrum Aiyer (USPTO) • Tom Kalil (OSTP) • Kathy Hudson (NIH) • Dina Paltoo (NIH) • Al Bonnema (DoD) • Michael Balint (PIF) • Kara DeFrias (OVP) • Greg Pappas (FDA) • Erin Szulman (OSTP) • Paula Jacobs (NCI)
- 29. NCI Genomic Data Commons launched at ASCO on June 6, 2016 https://gdc-portal.nci.nih.gov 2.6 PB of legacy data and 1.5 PB of harmonized data.
- 30. At the June 29th Cancer Moonshot Summit, Foundation Medicine announced the release of 18,000 genomic profiles to the NCI GDC
- 31. TCGA 11,353 cases TARGET 3,178 cases Current Foundation Medicine 18,000 cases Cancer studies in dbGaP ~4,000 cases Multiple Myeloma RF ~1,000 cases AACR GENIE 59,000 cases Coming soon NCI-MATCH ~3,000 cases Clinical Trial Sequencing Program ~3,000 cases Planned (1-3 years) Cancer Driver Discovery Program ~5,000 cases Human Cancer Models Initiative ~1,000 cases APOLLO – VA and DoD ~8,000 cases ~117,000 cases 10/17/2017 NCI-CPTAC ~1,000 cases
- 32. 0 1000 2000 3000 4000 5000 6000 7000 8000 9000 10000 2013 2014 2015 2016 2017 2018 2019 2020 #oftumorsamples Projected Reality Moonshot? (Agency and International Collaborations) 2009 2016
- 33. Defining mechanisms, targets, and lead molecules New methods of diagnosis, treatment, and prevention Delivery of recommended and timely care to the right patient True Benefit to society Controlled studies leading to effective care Translational from basic science to human studies Translational of new interventions into the clinic and health decision making Proteogenomics Characterization Centers (PCC) 2016 2026 Proteogenomics Translational Research Centers (PTRC) VA DoD
- 34. https://medium.com/cancer-moonshot/ Col. Craig Shriver, MD Jennifer Lee, MD Henry Rodriguez, PhD, MBA 5/26/16
- 36. Patients with new or recurrent cancer diagnosis Veterans Active Duty & DoD Beneficiaries Civilians Consents to VA/DoD/NCI APOLLO research program The American Genome Center Co-enroll MVP Proteogenomics Characterization (~8,000 patients) CPTAC PCC + MCC PRO / IHC Residual tissue for CLIA-approved targeted sequencing (CATS) VA ORD and NCI- sponsored Clinical Trials NCI CTEP/CPTAC PTRC VA Hospitals Murtha Cancer Center Clinical Phenotype & outcomes Data aggregation, analysis, and sharing to rapidly improve outcomes for active duty, beneficiaries, veterans, and civilians Murtha Cancer Center VA Hospitals Adaptive Learning Healthcare System Clinical Data Research Data APOLLO – Applied Proteogenomics OrganizationaL Learning and Outcomes consortium DaVINCI Registry DPALS CATS
- 38. APOLLO
- 39. 7/17/2016 “…proteogenomics, which is -- as I used a metaphor -- it’s like the genes are the full roster of a basketball team….but the winning strategy comes from finding out who their starting lineup is. The proteins are the starters you're going to play against -- the five you are going to have to defend against I’m pleased to say, Mr. Prime Minister, that we've signed three memorandums of understanding between our two nations …we're going to be able to share patient histories, proteogenomics and clinical phenotypes data -- data on various proteins and genetic characteristics of almost 60,000 patients in Australia and the United States with full privacy protections… And I predict that you're going to see this repeated around the world.” - Vice President Biden, Australia https://www.whitehouse.gov/the-press-office/2016/07/16/fact- sheet-victoria-comprehensive-cancer-center-vice-president-biden
- 42. NCI Proteomic Data Commons CPTAC APOLLO ICPC Proteogenomics Data Generation SFTP site Internal Jamboree Proteomic Data Commons Research Community 01001110 01000011 01001001 Adapted from Hinkson, et al. Front. Cell Dev. Biol 9/16/2017 Izumi Hinkson, PhD
- 44. Finding the Right “Needle” at the Right “Time” of Disease
- 47. APOLLO
- 48. Modified from Abernethy et. al. JCO 2010
- 50. $? Outcome?
- 51. Big Data Scientist Training Enhancement Program (BD-STEP) Graduates of BD-STEP would: • have skillsets to perform next-generation patient- centered outcomes research by manipulating and analyzing large-scale, multi-element, patient data sets to develop novel disease signatures or unique performance-based clinical benchmarks • have an understanding of real-time, performance- driven health care delivery in the VA systems Michelle Berny-Lang, NCIConnie Lee, VHA/EES
- 52. BD-STEP Sites and Fellows: 2016-2018
- 54. Example #1 Industry (6) Government (8) Jan 2014
- 56. August 2017
- 57. Example #2 June 2017 – November 2017
- 58. https://www.synapse.org/#!Synapse:syn8228304/wiki/413428 504 participants 37 countries 6 continents
- 60. Data sharing in other research communities norbert.tavares@nih.gov
- 61. Acknowledgements/Thanks to the “Secret Ingredients” Clinical Sciences Physical Sciences Life Sciences
- 62. Learn More About Us… http://cssi.cancer.gov jerry.lee@nih.gov @NCI_CSSI @jleePSOC Norbert Tavares, PhD norbert.tavares@nih.gov