Unlocking Our Treasures Enhancing Access to Tissue for Genomics Research Henry Chueh Massachusetts General Hospital Harvard Medical School Internet2 Member Meeting Austin, Texas September 30, 2004

“ Be careful of reading health books. You may die of a misprint.” Mark Twain

Genetic alphabet AT GC

Mutations Image credit: U.S. Department of Energy Human Genome Program,

Molecular foundation of disease Image credit: U.S. Department of Energy Joint Genome Institute

Epithelial Growth Factor Receptor Angiogenesis Metastasis EGFR Tyrosine Kinase Receptor Invasion Proliferation K K EGFR-TK Inhibitor Cell membrane Image credit: Modified from Astra-Zeneca educational materials

Lynch, T. J. et al. N Engl J Med 2004;350: Clustering of Mutations in the EGFR Gene at Critical Sites within the ATP-Binding Pocket

Genomics research  Clinical research in the genomics era requires, at a minimum:  Access to diseased and healthy tissue  Clinical information associated with the tissue (demographics, outcomes, etc)

Shared Pathology Information Network

SPIN Collaborators  National Cancer Institute (NCI)  Children’s Hospital  Massachusetts General Hospital  Brigham and Women’s Hospital  Dana-Farber Cancer Institute  Beth Israel Hospital  UCLA Medical Center  Regenstrief Institute  Univ. of Pittsburgh Medical Center

SPIN Themes  Think “framework”  Specifications clear enough to develop products independently  Local control  Network planning

SPIN: p2p Model Assumptions  No ongoing aggregation of data, no central repository to govern  Provision of data into a SPIN node from systems internal to the institution is managed locally with SPIN tools  Any information search by any SPIN Query Tool is HIPAA Privacy Rule compliant

SPIN Network Today MGHUCLA HMS CH BI BWH UPMC HMS Tissue Banks (other) OliveViewCedars RI SPIN VSL Running type A SPIN node software Running type B SPIN software Link established Link planned VA

SPIN: Key Activities  Join: Become a member of the network  Host: Provision clinical, specimen data  Search: Locate specimens  Acquire: Obtain specimens

SPIN Host / Search: Data Flow SPIN node De-identified Limited Data Set Institutional Firewall SPIN Query SPIN Response Anonymous or De-identified Data Set InternetIntranet SPIN ProtocolsSPIN Node Software Source Systems Identified Data SPIN Loading Tools Source Systems Clinical Systems Codebook Internal Threshold

Clinical reports to coded annotations … Right colon Chronic colitis Active Mild …

SPIN Query Propagation and Response MGHUCLA BI BWH Query Server SPIN CH SPIN XML request Compose query using a Web browser SPIN request propagates SPIN peer responses return directly to originating SuperNode UPMC RI Cedars SPIN (aggregate) XML Response

Clinical Research Scenarios  ? Rare subset of non-small cell lung cancer (NSCLC) shares common mutation that would make it more susceptible to certain novel therapeutics  ? Infection with herpes zoster (chickenpox) virus enhances mutagenicity in lung cancer

SPIN Open Architecture  Accommodates alternative node and query server implementations  Will accommodate additional data models and schema:  Clinical data (symptoms, outcomes, etc)  Clinical imaging data (MRI, CT scans, etc)  Molecular biology data (microarray data, etc)  Pathology imaging

What’s ahead?  Bringing phenotypes in juxtaposition with genotypic information  NIH roadmap initiatives to include integrated biomedical computing  In silico experiments and analysis

Acknowledgements  Jules Berman (NCI)  Isaac Kohane  Clem McDonald  Jonathan Braun  Michael Becich  Ulysses Balis  David Berkowicz  David Korn (AAMC)  Elias Zerhouni (NIH)

Image credit: U.S. Department of Energy Human Genome Program,