Unlocking Our TreasuresUnlocking Our TreasuresEnhancing Access to Tissue for Genomics ResearchEnhancing Access to Tissue for Genomics Research

Henry ChuehHenry ChuehMassachusetts General HospitalMassachusetts General Hospital

Harvard Medical SchoolHarvard Medical School

Internet2 Member MeetingInternet2 Member MeetingAustin, TexasAustin, Texas

September 30, 2004September 30, 2004

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

Mark Twain

Genetic alphabetGenetic alphabet

ATGC

MutationsMutations

Image credit: U.S. Department of Energy Human Genome Program, http://www.ornl.gov/hgmis

Molecular foundation of diseaseMolecular foundation of disease

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

Epithelial Growth Factor ReceptorEpithelial Growth Factor Receptor

AngiogenesisMetastasis

EGFR TyrosineKinase Receptor

Invasion

Proliferation

K KEGFR-TK Inhibitor

Cell membrane

Image credit: Modified from Astra-Zeneca educational materials

Lynch, T. J. et al. N Engl J Med 2004;350:2129-2139

Clustering of Mutations in the EGFR Gene at Critical Sites within the ATP-Binding Pocket

Genomics researchGenomics research

Clinical research in the genomics era Clinical research in the genomics era requires, at a minimum:requires, at a minimum:

Access to diseased and healthy tissueAccess to diseased and healthy tissue Clinical information associated with the tissue Clinical information associated with the tissue

(demographics, outcomes, etc)(demographics, outcomes, etc)

Shared Pathology Information NetworkShared Pathology Information Network

SPIN CollaboratorsSPIN Collaborators

National Cancer Institute (NCI)National Cancer Institute (NCI) Children’s HospitalChildren’s Hospital Massachusetts General HospitalMassachusetts General Hospital Brigham and Women’s HospitalBrigham and Women’s Hospital Dana-Farber Cancer InstituteDana-Farber Cancer Institute Beth Israel HospitalBeth Israel Hospital UCLA Medical CenterUCLA Medical Center Regenstrief InstituteRegenstrief Institute Univ. of Pittsburgh Medical CenterUniv. of Pittsburgh Medical Center

SPIN ThemesSPIN Themes

Think “framework”Think “framework” Specifications clear enough to develop Specifications clear enough to develop

products independentlyproducts independently Local controlLocal control Network planning Network planning

SPIN: p2p Model AssumptionsSPIN: p2p Model Assumptions

No ongoing aggregation of data, no central No ongoing aggregation of data, no central repository to governrepository to govern

Provision of data into a SPIN node from Provision of data into a SPIN node from systems internal to the institution is systems internal to the institution is managed locally with SPIN toolsmanaged locally with SPIN tools

Any information search by any SPIN Any information search by any SPIN Query Tool is HIPAA Privacy Rule Query Tool is HIPAA Privacy Rule compliantcompliant

SPIN Network TodaySPIN Network Today

MGHUCLA

HMS

CH

BI

BWH

UPMC

HMS Tissue Banks

(other)OliveView

Cedars

RI

SPIN

VSL

Running type A SPIN node software

Running type B SPIN software

Link established

Link planned

VA

SPIN: Key Activities SPIN: Key Activities

Join: Become a member of the networkJoin: Become a member of the network

Host: Provision clinical, specimen dataHost: Provision clinical, specimen data

Search: Locate specimensSearch: Locate specimens

Acquire: Obtain specimensAcquire: Obtain specimens

SPIN Host / Search: Data FlowSPIN Host / Search: Data Flow

SPIN node

De-identified Limited Data Set

InstitutionalFirewall

SPIN Query

SPIN ResponseAnonymous or

De-identified Data Set

Internet Intranet

SPIN Protocols SPIN Node Software

SourceSystems

Identified Data

SPIN Loading Tools

SourceSystemsClinicalSystems

Codebook

InternalThreshold

Clinical reports to coded annotationsClinical reports to coded annotations

…<Specimen> <Topology> <Term Code="C0227375" Source="UMLS">Right colon</Term> </Topology> <Diagnosis> <Term Code="C0267375" Source="UMLS">Chronic colitis</Term> <Modifier Code="C0205177" Source="UMLS">Active</Modifier> <Modifier Code="C0205080" Source="UMLS">Mild</Modifier> </Diagnosis> <Diagnosis> …

Part II:Received in formalin, labeled with the patient’s name, medical record number and

“Appendix (detached)” is a 3.2 x 1.4 x 1.1 cm appendix submitted separately from themain ileocolectomy specimen. The serosal surface appears smooth, purple, andglistening. Serial sectioning reveals no mucosal abnormalities, ulcerations, thickening, orperforations. The periappendiceal tissue appears grossly normal. The both halves of thebisected tip, and sections through the body of the appendix are submitted in Block A.

Diagnosis:

I. Right colon, Ileocolectomy:1. Invasive, poorly differentiated Adenocarcinoma (see synoptic

report)Comment: Though an abundant amount of extracellularmucin is present in the sections examined, less that 50% ofthe malignant cells display mucinous features, thus thecriteria for classification of this tumor as mucinous type ofcolonic adenocarcinoma are not fulfilled.

2. Adenoma with high-grade dysplasia.Note: The dysplasia is located superficially in the colonicepithelium in the sections examined. No invasion into thelamina propria or stalk is noted.

3. Mild chronic active colitis.4. Colonic stricture with transmucosal fibrosis.

II Appendix:1. Intramucosal mucus pool, no evidence of colonic

adenocarcinoma seen.2. Carcinoid tumor, benign. 0.5 cm

Note: Immunohistochemical studies performed on carcinoidtumor cells will be reported in an addendum.

ŅColon Cancer SynopsisÓ

SPIN Query Propagation and ResponseSPIN 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

UPMCRI

Cedars

SPIN (aggregate) XML Response

Clinical Research ScenariosClinical Research Scenarios

? Rare subset of non-small cell lung cancer ? Rare subset of non-small cell lung cancer (NSCLC) shares common mutation that (NSCLC) shares common mutation that would make it more susceptible to certain would make it more susceptible to certain novel therapeuticsnovel therapeutics

? Infection with herpes zoster (chickenpox) ? Infection with herpes zoster (chickenpox) virus enhances mutagenicity in lung cancervirus enhances mutagenicity in lung cancer

SPIN Open ArchitectureSPIN Open Architecture

Accommodates alternative node and query Accommodates alternative node and query server implementationsserver implementations

Will accommodate additional data models Will accommodate additional data models and schema:and schema: Clinical data (symptoms, outcomes, etc)Clinical data (symptoms, outcomes, etc) Clinical imaging data (MRI, CT scans, etc)Clinical imaging data (MRI, CT scans, etc) Molecular biology data (microarray data, etc)Molecular biology data (microarray data, etc) Pathology imagingPathology imaging

What’s ahead?What’s ahead?

Bringing phenotypes in juxtaposition with Bringing phenotypes in juxtaposition with genotypic informationgenotypic information

NIH roadmap initiatives to include integrated NIH roadmap initiatives to include integrated biomedical computingbiomedical computing

In silico experiments and analysisIn silico experiments and analysis

AcknowledgementsAcknowledgements

Jules Berman (NCI)Jules Berman (NCI) Isaac KohaneIsaac Kohane Clem McDonaldClem McDonald Jonathan BraunJonathan Braun Michael BecichMichael Becich Ulysses BalisUlysses Balis David BerkowiczDavid Berkowicz David Korn (AAMC)David Korn (AAMC) Elias Zerhouni (NIH)Elias Zerhouni (NIH)

Image credit: U.S. Department of Energy Human Genome Program, http://www.ornl.gov/hgmis