national cancer data ecosystem and data sharing
TRANSCRIPT
NCI Support for a National Cancer Data
Ecosystem and Data SharingWarren Kibbe, PhD
@wakibbe
February 6th, 2017
2
To develop the knowledge base that will lessen the burden of
cancer in the United States and around the world.
NCI Mission
3
Cancer Statistics
In 2016 there were an estimated
1,700,000 new cancer cases and
600,000 cancer deaths- American Cancer Society 2015
Cancer remains the second most common cause of death in the U.S.
- Centers for Disease Control and Prevention 2015
4
Understanding Cancer
Precision medicine will lead to fundamental understanding of the complex interplay between genetics, epigenetics, nutrition, environment and clinical presentation and direct effective, evidence-based prevention and treatment.
5
Cancer is a grand challenge
Deep biological understanding
Advances in scientific methods
Advances in instrumentation
Advances in technology
Data and computation
Cancer Research and Care generatedetailed data that is critical to create a learning health system for cancer
Requires:
6
7
8
Biological Scales
10
Digital technology is changing rapidly
11
Cancer therapy is changing
12
Application of Cancer Genomics is changing
13
The Beau BidenCancer Moonshot
How do we enable meaningful, patient-centered and patient-level
data sharing for cancer and promote access to clinical trials for
all Americans?
14
Goals of the Beau Biden Cancer Moonshot
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(Presidential Memo 2016)
15
A Few Beau Biden Cancer Moonshot Milestones• Announced by Former President Obama at the State of the Union January 12, 2016
• Blue Ribbon Panel convened at AACR, April 18, 2016
• Genomic Data Commons went public June 6, 2016
• Vice President’s Cancer Moonshot Summit – June 29, 2016
• Rethinking Clinical Trial Search – Open API at https://clinicaltrialsapi.cancer.gov • Blue Ribbon Panel recommendations – accepted by the National Cancer Advisory
Board on September 7th, 2016
• Cancer Moonshot Task Force and BRP recommendations sent to President on October 17th, 2016 https://www.cancer.gov/research/key-initiatives/moonshot-cancer-initiative/milestones and released at https://cancer.gov/brp
• 21st Century Cures Act funding the Beau Biden Cancer Moonshot passed 94-5 by the Senate on December 8 and signed by Former President Obama December 13, 2016.
16https://cancer.gov/brp
Blue Ribbon Panel Recommendations
Network for Direct Patient Engagement Cancer Immunotherapy Translational Science Network Therapeutic Target Identification to Overcome Drug Resistance A National Cancer Data Ecosystem for Sharing and Analysis Fusion Oncoproteins in Childhood Cancers Symptom Management Research Prevention and Early Detection – Implementation of Evidence-based Approaches Retrospective Analysis of Biospecimens from Patients Treated with Standard of Care Generation of 4D Human Tumor Atlas Development of New Enabling Cancer Technologies
18
Relationship Between Bypass Budget and Blue Ribbon Panel Report Bypass Budget addresses NCI’s
entire research portfolio
Lays out the plan for NCI’s continued investment in cancer research
Cancer Moonshot is a unique opportunity to enhance cancer research in specific areas that are poised for acceleration
The BRP report made 10 bold, yet feasible, recommendations that will fast-track initiatives if infused with Moonshot funding
Cancer Research Data Ecosystem
@wakibbe
20
Changing the conversation around data sharing
How do we find data, software, standards? How can we make data, annotations, software, metadata accessible? How do we increase data reuse? Reproducibility? How do we make more data machine readable?
NIH Data CommonsNCI Genomic Data Commons
National Cancer Data Ecosystem
Data Commons co-locate data, storage and computing infrastructure, and frequently used tools for analyzing and sharing data to create an
interoperable resource for the research community.*Robert L. Grossman, Allison Heath, Mark Murphy, Maria Patterson, A Case for Data Commons Towards Data Science as a Service, to appear. Source of image: Interior of one of Google’s Data Center, www.google.com/about/datacenters/.
Cancer Research Data Ecosystem – Cancer Moonshot BRP
Well characterized research data
sets
Cancer cohorts Patient data
EHR, Lab Data, Imaging, PROs, Smart Devices,
Decision Support
Learning from everycancer patient
Active researchparticipation
Research informationdonor
Clinical ResearchObservational studies
ProteogenomicsImaging dataClinical trials
Discovery Patient engaged Research
SurveillanceBig Data
Implementation research
SEERGDC
22
Principles for the Cancer Research Data Ecosystem
• Open Science. Supporting Open Access, Open Data, Open Source, and Data Liquidity for the cancer community
• Standardization through CDEs and Case Report Forms
• Interoperability by exposing existing knowledge through appropriate integration of ontologies, vocabularies and taxonomies
• Consistency of curation and capture of evidence (tissue types, recurrence, therapy – including genomic, epigenomic, etc context)
• Sustainable models for informatics infrastructure, services, data, metadata
23
Cancer Data Sharing& Data Commons
• Support open science • Support data reusability• Aligned with Cancer Moonshot• Part of Precision Medicine• Reduce Health Disparities• Improve patient access to clinical
trials• Work toward a learning National
Cancer Data Ecosystem
Reduce the risk, improve early detection, outcomes and survivorship in cancer
24
Data Commons Structure
Data Contributors and Consumers
Researchers PatientsCliniciansInstitutions
NCI ThesauruscaDSR
NLM UMLSRxNormLOINC
SNOMED
25
The Cancer Genomic Data Commons (GDC) is an existing effort to standardize and simplify submission of genomic data to NCI and follow the principles of FAIR – Findable, Accessible, Attributable, Interoperable, Reusable, and Provide Recognition.
The GDC is part of the NIH Big Data to Knowledge (BD2K) initiative and an example of the NIH Commons
Genomic Data Commons
Microattribution, nanopublications, tracking the use of data, annotation of data, use of algorithms, supports
the data /software /metadata life cycle to provide credit and analyze impact of data, software, analytics,
algorithm, curation and knowledge sharing
Force11 white paperhttps://www.force11.org/group/fairgroup/fairprinciples
NCI Genomic Data Commons The GDC went live on June 6, 2016 with approximately 4.1 PB of data. This includes:
2.6 PB of legacy data
1.5 PB of “harmonized” data
577,878 files about 14194 cases (patients), in 42 cancer types, across 29 primary sites.
10 major data types, ranging from Raw Sequencing Data, Raw Microarray Data, to Copy Number Variation, Simple Nucleotide Variation and Gene Expression.
Data are derived from 17 different experimental strategies, with the major ones being RNA-Seq, WXS, WGS, miRNA-Seq, Genotyping Array and Expression Array.
Foundation Medicine announced the release of 18,000 genomic profiles to the GDC at the Cancer Moonshot Summit.
Genomic Data Commons Data Portal
GDC Content
GDC
TCGA11,353 cases TARGET 3,178 cases
Current
Foundation Medicine 18,000 cases Cancer studies in dbGAP ~4,000 cases
Coming soon
NCI-MATCH ~5,000 cases Clinical Trial Sequencing Program ~3,000 cases
Planned (1-3 years)
Cancer Driver Discovery Program ~5,000 cases Human Cancer Model Initiative ~1,000 cases APOLLO – VA-DoD ~8,000
cases
~58,000 cases
Exome-seq
Whole genome-seq
RNA-seq
Copy number
Genomealignment
Genomealignment
Genomealignment
Datasegmentation
1° processing
Mutations
Mutations +structural variants
Digital geneexpression
Copy numbercalls
2° processingOncogene vs.
Tumor suppressor
Translocations
Relative RNA levelsAlternative splicing
Gene amplification/ deletion
3° processing
GDC Data HarmonizationMultiple data types and levels of processing
Mutect2pipeline
GDC Data HarmonizationOpen Source, Dockerized Pipelines
Recoveryrate
(% true positives) A0F0
SomaticSniper 81.1% 76.5%VarScan 93.9% 84.3%
MuSE 93.1% 87.3%All Three 96.4% 91.2%
GDC variant callingpipelinesWash UBaylorBroad
GDC Data HarmonizationMultiple pipelines needed to recover all variants
Development of the NCI Genomic Data Commons (GDC)To Foster the Molecular Diagnosis and Treatment of Cancer
GDC
Bob Grossman PIUniv. of Chicago
Ontario Inst. Cancer Res.Leidos
Institute of MedicineTowards Precision Medicine
2011
Discovery of Cancer Drivers With 2% Prevalence
Lung adeno.+ 2,900
Colorectal+ 1,200
Ovarian+ 500
Lawrence et al, Nature 2014
Power Calculation for Cancer Driver Discovery
Need to resequence >100,000 tumors to identify all cancer drivers at >2% prevalence
What Makes GDC Special? Stores raw genomic data, allowing continuous reanalysis as
computation methods and genome annotations improve
NCI commitment to maintain long-term storage of cancer genomic data in the GDC with free access to researchers
Utilizes shared bioinformatic pipelines to facilitate cross-study comparisons and integrated analysis of multiple data types
Maintains harmonized clinical data in a highly structured and extensible schema
Enables researchers to comply with the NIH Genomic Data Sharing policy as well as journal requirements for data sharing
GDC The explanatory power of data in the GDC will grow over time as
it accrues more cases => GDC will promote precision oncology
Other Cancer Data Sharing EffortsSignature Efforts Data
BRCA ChallengeSomatic variant sharing
Isolated genetic variantsNo raw sequencing data
Precision medicine questionsSomatic variant sharing
Panel gene resequencingClinical response
Clinical trialPublic-private partnerships
Comprehensive genomicsDetailed clinical
phenotype data
Clinical trial accessClinical/genomic data aggregation
EHR dataClinical sequencing
Clinical oncology standardsEHR dataClinical sequencing
GDC
Utility of a Cancer Knowledge System
Identifylow-frequencycancer drivers
Define genomicdeterminants of response
to therapy
Compose clinical trialcohorts sharing
targeted genetic lesions
Cancerinformation
donors
GenomicData
Commons
Towards a Cancer Knowledge System Continue genomic investigations of cancer
• Need > 100,000 cases analyzed• Embrace all genomic platforms• Relationship of relapse and primary biopsies
Incorporate associated clinical annotations• Clinical trial data• Observational, longitudinal standard-of-care data• N-of-1 clinical data
Promote and curate biological investigations of cancer genetic variants• Driver vs. passenger mutations• Multiple phenotypic assays• Alterations in regulatory pathways – proteomics• Mechanisms of therapeutic resistance• Functional genomic investigations
Integrative models for high-dimensional data
GenomicData
Commons
40
Support the Precision Medicine Initiative
• Expand data model to include other data (e.g. imaging and proteomics)
• Allow easy publication of persistent links to data, annotations, algorithms, tools, workflows
• Measure usage and impact
• Change incentives for public contributions
The Genomic Data Commons and Cloud Pilots
41
PMI – Oncology, the GDC and the Cloud Pilots Goals
Support precision medicine-focused clinical research Enable researchers to deposit well-annotated
(Interoperable) genomic data sets with the GDC Provide a single source (and single dbGaP access
request!) to Find and Access these data Enable effective analysis and meta-analysis of these data
without requiring local downloads – data Reuse Understand Contributions, Assess value through usage,
and give Attribution to all users
42
PMI – Oncology, the GDC and the Cloud Pilots Goals
Provide a data integration platform to allow multiple data types, multi-scalar data, temporal data from cancer models and patients through open APIs Work with the Global Alliance for Genomics and Health
(GA4GH) to define the next generation of secure, flexible, meaningful, interoperable, lightweight interfaces – open APIs
Engage the cancer research community in evaluating the open APIs for ease of use and effectiveness
GDC AcknowledgementsNCI Center for Cancer Genomics Univ. of Chicago
Bob GrossmanAllison Heath
Mike FordZhenyu Zhang
Ontario Institute for Cancer Research
Lou StaudtZhining Wang
Martin FergusonJC Zenklusen
Daniela GerhardDeb Steverson
Vincent Ferretti'Francois Gerthoffert
JunJun Zhang
Leidos Biomedical ResearchMark Jensen
Sharon GaheenHimanso Sahni
NCI NCI CBIITTony KerlavageTanya Davidsen
CGC Pilot Team Principal Investigators • Gad Getz, Ph.D - Broad Institute - http://firecloud.org • Ilya Shmulevich, Ph.D - ISB - http://cgc.systemsbiology.net/ • Deniz Kural, Ph.D - Seven Bridges – http://www.cancergenomicscloud.org
NCI Project Officer & CORs• Anthony Kerlavage, Ph.D –Project Officer• Juli Klemm, Ph.D – COR, Broad Institute• Tanja Davidsen, Ph.D – COR, Institute for Systems Biology • Ishwar Chandramouliswaran, MS, MBA – COR, Seven Bridges Genomics
GDC Principal Investigator• Robert Grossman, Ph.D - University of Chicago• Allison Heath, Ph.D - University of Chicago• Vincent Ferretti, Ph.D - Ontario Institute for Cancer Research
Cancer Genomics Project Teams
NCI Leadership Team• Doug Lowy, M.D.• Lou Staudt, M.D., Ph.D.• Stephen Chanock, M.D.• George Komatsoulis, Ph.D.• Warren Kibbe, Ph.D.
Center for Cancer Genomics Partners• JC Zenklusen, Ph.D.• Daniela Gerhard, Ph.D.• Zhining Wang, Ph.D.• Liming Yang, Ph.D.• Martin Ferguson, Ph.D.
Cancer Research Data Ecosystem – Cancer Moonshot BRP
Well characterized research data
sets
Cancer cohorts Patient data
EHR, Lab Data, Imaging, PROs, Smart Devices,
Decision Support
Learning from everycancer patient
Active researchparticipation
Research informationdonor
Clinical ResearchObservational studies
ProteogenomicsImaging dataClinical trials
Discovery Patient engaged Research
SurveillanceBig Data
Implementation research
SEERGDC
46
Data Commons Structure
Data Contributors and Consumers
Researchers PatientsCliniciansInstitutions
NCI ThesauruscaDSR
NLM UMLSRxNormLOINC
SNOMED
48
Rethinking Cancer Clinical Trials Search
for patients and providers
Rethinking Clinical Trials Search
Engaging the Presidential Innovation Fellows Create an Application Programming Interface (API) for Clinical Trials Create an example search interface based on the API Create a twitter feed for all new clinical trials Incorporation of these innovations into cancer.gov
2/6/17
50
Rethinking and Enhancing Clinical Trial Search: June, 2016• Initial Release of an API (Application Programming Interface) (API)1, developed by the
Presidential Innovation Fellows, for testing. This tool, found at https://clinicaltrialsapi.cancer.gov, makes publicly available trial registration information from the CTRP database, currently found on cancer.gov, assessable to third-party innovators so that they can build new digital tools tailored to the clinical trial search needs of their users.
• Launch of @NCICancerTrials on Twitter and dissemination of clinical trial information via GovDelivery: https://public.govdelivery.com/accounts/USNIHNCI/subscriber/new
• Changes the Cancer.gov Website to enhance clinical trial searching
1A set of protocols designed to provide communication between a software application and a computer operating system or between applications.
Rethinking Clinical Trial Search – Next Steps
• Cancer.gov
- Work with the CTAC Clinical Trials Informatics Working Group (CTIWG) on the design on a “front end” to the API for use on the Cancer.gov website.- This will allow search and retrieval of information that is currently available on
Cancer.gov directly from NCI’s Clinical Trials Reporting Program
- The CTIWG will provide input regarding design and usability of the Cancer.gov website, as well as:- Prioritization of requested enhancements (e.g., structured eligibility criteria)
• Other websites and/or providers of clinical trial search
- Test API and use publicly assessable CTRP data for use in their systems.
Clinical Trials Search API https://clinicaltrialsapi.cancer.gov
2/6/17
https://clinicaltrialsapi.cancer.gov/clinical-trial/NCI-2014-01509
2/6/17
2/6/17
2/6/17
2/6/17
2/6/17
59
www.cancer.gov www.cancer.gov/espanol
62
NIH Genomic Data Sharing Policy
https://gds.nih.gov/ Went into effect January 25, 2015
NCI guidance:http://
www.cancer.gov/grants-training/grants-management/nci-policies/genomic-data
Requires public sharing of genomic data sets