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The NCI Integrated Canine Data Commons (ICDC): an Update

The NCI Integrated Canine Data Commons (ICDC): an Update. Toby T. Hecht, Ph.D. Deputy Director, NCI Division of Cancer Treatment and Diagnosis Consortium for Canine Comparative Oncology (C3O)Symposium February 15, 2019. I have no disclosures or conflicts to report. What will be discussed:.

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The NCI Integrated Canine Data Commons (ICDC): an Update

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  1. The NCI Integrated Canine Data Commons (ICDC): an Update Toby T. Hecht, Ph.D. Deputy Director, NCI Division of Cancer Treatment and Diagnosis Consortium for Canine Comparative Oncology (C3O)Symposium February 15, 2019

  2. I have no disclosures or conflicts to report

  3. What will be discussed: • What is the ICDC and why do we need it? • How is it being set up? What are the data sources? • How will it interact with human genomic and other databases? • How will it be used by investigators? • Where are we now, and what’s ahead in the future?

  4. Overarching Question for the NCI: Can pet dogs with spontaneous cancers serve as close models of human disease in order to evaluate new drugs, immunotherapeutic agents, and combinations, for further development for human cancer patients?

  5. One Approach to Answering this Question • Establish a publicly accessible canine database as an inter-operable node in the larger human NCI Cancer Research Data Commons (CRDC) that would contain: • Full genotype and phenotype characterization of the major canine tumors (and normal tissues) including tumor mutational burden (TMB) and neoantigens (seen by T cells in the context of canine MHC antigens) • Description of the tumor microenvironment (TME) including numbers and types of subsets of immune (and other) cells • Clinical data from COTC and other canine cancer trials (including images) • Including all the clinical data elements for canines

  6. Key NCI Focus Areas

  7. Background and Initial Resources for the ICDC In recent years, there have been 2 NCI initiatives that informed the ICDC: • A supplement to 8 Cancer Center Support Grants (P30s) to work with veterinary oncologists and geneticists to: • Sequence 25 cases of one of more of the following canine tumors and their normal equivalents: B-cell lymphoma, melanoma, glioma, bladder cancer, osteosarcoma, and mammary cancer • Determine the tumor mutational burden (TMB) and identify neoantigens that can strongly bind canine MHC antigens • Characterize T cell subsets and numbers, as well as other relevant aspects of the TME • An RFA that supports a network of canine clinical studies using immunotherapeutic agents and novel drug combinations (e.g., other immune modulators, molecular targeted agents, chemotherapy, and radiation) plus laboratory correlative studies that seek to describe, characterize and understand the cellular and molecular mechanisms that determine the anti-tumor response (or non-response) in dogs with spontaneous tumors. 6 cooperative agreements were awarded including a coordinating center.

  8. Prediction of clinical responses to immune checkpoint inhibitors based on tumor mutational burden (TMB) Samstein, et al; Nature Genetics; https://doi.org/10.1038/s41588-018-0312-8 Months

  9. Components: • Data Nodes • Data Commons Framework • Data Aggregators • Cloud Resources • Application Programming • Interfaces (APIs) • Elastic compute resources • Portals • Workspaces • Analytic Tools • Tool repositories Data Sources: TCIA Canine Immuno-oncology studies Clinical The Cancer Imaging Archive* Clinical Proteomics Tumor Analysis Consortium* Canine Studies

  10. Work Scope and Timeline of the ICDC

  11. Major Parts of the Project for Milestone 1 (Prototype)

  12. DCTD Frederick Task Order Leidos Technical Project Managers: FNL/CBIIT support FNL/DCTD support Integrated Canine Data Commons Leidos Contract + NCI CBIIT + subcontractors as needed to stand up a prototype (as the basic task) Leidos Subcontract to set a Steering Committee (SC): 10 NIH 10 Academic/Industry 3 Leidos Review, modify design and operations, define and refine data models and end user tools • Obtain canine-specific design criteria and data models from the SC • Adapt the infrastructure from the Cancer Research Data Commons (CRDC), customize for canine with input from the SC, and prepare tools for cloud analysis • Test and validate this “1st Prototype” with an existing canine dataset(s) for performance that is inter-operable with the CRDC • Load datasets from the supplements and other sites (after publication) and verify performance • Refine and update; validate all systems; launch public accessible ICDC; add data, maintenance. Statementof Work Tasks SC End User Working Group (SCWG) Research staff at SC institutions (supplements or subcontracts) Compile and curate canine datasets with clinical outcomes (if available) for validation exercise and testing; establishment of a reference genome considering various breeds Curate and upload canine trial data (genomics, PD, path, clinical and imaging), access, and query • Collect and provide other curated datasets with clinical outcomes (if available) from: • Canine Immunotherapy Trials Network • P30 Supplement Sites • Other sites • NHGRI Expand the curation and uploading of canine study data

  13. What has been accomplished so far (4 months)? • Steering Committee Activities • Finalized: 23 members 10 NIH/10 Extramural/3 FNLCR • Subcontracts are being established • First meeting at the end of February • Data Activities • A first data model has been chosen—based on a COTC trial—and will be tested • Starting to receive data from NCATS: genomic sequences, proteomics—establishing import mechanisms. Eventually, users will submit their own data. • Others have relevant data and are willing to contribute • Gathering use cases • Software Activities • Configuring the ICDC infrastructure and the data model to work within a modified Gen3 software system • NCI CloudOne (AWS) was selected as the prototype’s cloud infrastructure. Meeting with cloud resources to understand establishment of interoperability • Working with the semantics team

  14. Data Sources for the ICDC Prototype • Canine Sequences from Collaboration of COP, NCSU, CSU, and NCATS • 5 Tumor types: B cell lymphoma; T cell lymphoma; melanoma; osteosarcoma; pulmonary carcinoma • Number of cases: 12 for each plus normal pairs • Data from all cases: WGS, RNAseq, and proteomics (from tumor and serum) • Project team: NCATS (analysis), CSU group (patients), Matthew Breen’s group in NCSU (sequencing), Amy LeBlanc (patients)

  15. What’s next? • The ICDC Prototype development is fully funded and should take until September 2020. • Parts of Option 1—the Production Phase—should be able to start by September 2019. • Requesting new funds from the NCI to complete Milestones 2 and 3 because of the fast pace of Milestone 1.

  16. “I would argue that no matter what your interest in cancer research, it is empowered by big data. My strategy for big data is to create large, linked, multimodal data sets that have histology, radiology, genetics, and clinical outcomes.” Ned Sharpless, NCI Director

  17. Questions???

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