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
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)
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)