transmart community meeting 5-7 nov 13 - session 3: characterization of the cell phenotypes involved...
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tranSMART Community Meeting 5-7 Nov 13 - Session 3: Characterization of the cell phenotypes involved in metastasis Characterization of the cell phenotypes involved in metastasis: Using tranSMART to enable high-throughput heterogeneous data integration and analysis Brian Athey, University of MichiganTRANSCRIPT
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tranSMART Overview University of Michigan-
Johns Hopkins University- Collaboration Brian D. Athey UM
Kenneth J. Pienta JHU Kevin A. Smith UM
Terry E. Weymouth UM 6 November 2013
Sanofi tranSMART Paris Meeting
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Presentation Outline
• Motivating & Conceptual Background • tranSMART at Johns Hopkins University
– Overall Scope – Scope of Pienta-Athey Lab Collaborative Demonstration Project
• Digital Microscopy Service, NCIBI tools and data, EMT-MET Transformation
• Future: Establishing and harmonizing databases across The Brady Institute
• Future: Evaluating PE or IDBS Electronic Laboratory Notebook (ELN) integration; Institutional level
• tranSMART at Michigan – PerkinElmer (PE) Spotfire Collaboration – Current and Future
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Biomedical Engineering
Historical Data
Registries
OpenClinica
Velos
BioDBX
RedCAP
Research Data Warehouse
Messaging Bus, ETL & External Collaboration Services (SOA, caGRID, SHRINE, ...) Vocabulary & Terminology Mapping Services (ICD-9/10 SNOMED, IMO, caDSR, ...)
Common Identifier Services (Patient, Provider, Research, Specimens, External Mappings) HIPAA/IRB Services (Honest Broker, DE-ID Consent Management, …)
Epic Clarity
HIM/ Documentation
Radiology
Pathology
Pharmacy
CareLink/ Eclipsys
Others…
Scheduling
Revenue Cycle
Emergency Med.
Ambulatory
International Data Sharing with External Collaborators
CTSAs caBIG TCGA
ULAM
Tissue Biorepositories
Metabolomics
Proteomics
Bioinformatics
Next-Gen Sequencing
Collexis
eThority (billing)
Click Commerce
(IRB)
Research Pre, Post- Award
Industry: Pharma/ Biotech I2b2/
SHRINE
Others …
Demographics
Diseases
Individuals
Populations
Portals / Providers, Payors, P. Health D
atabases / HIEs / N
HIN
IT S
ERC
UIR
TY
Cam
pus
Syst
ems
IT Security
HSDW
i2b2
High Performance
Cloud Computing & Data Storage
IT S
ecur
ity
• Reporting • Visualization • Analysis & • Data Mining
IT Security Brian Athey
& ECRIT 1/11/11
Health Sciences Library
Resources
NIH-Specific & External Data
Resources (PubMed, GenBank,
KEGG, GO, etc.)
SPORES
Others
Clinical Analysis
Database (CAD)
UMHS Data Architecture Unifying the Three Missions: Education, Research, & Patient Care
Visiting Student Application Service(VSAS)
M-Pathways
Ctools/Saki 3
Curriculum Eval. System
Clinical Scheduling & Grading System
Comprehensive Clinical Assessment Exam
Admissions
CAD CDR Education
Knowledge Repository
Research Administration
Data Warehouse
Research Administration
Systems
Research
Core Facilities/ ‘Omics’
Research Data
Management Systems
Research & Quality Metrics
Data Marts
Quality Metrics
Reporting&
Peer Review
Patient Care Systems Legacy+/Epic EHR
Enterprise Federated Data Warehouse
Service-Oriented Information Bus
Education
Bioinformatics and Systems Biology Workbenches
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Biomedical Engineering
Historical Data
Research Data
Management Systems
Registries
OpenClinica
Velos
BioDBX
RedCAP
Research Data Warehouse
Messaging Bus, ETL & External Collaboration Services (SOA, caGRID, SHRINE, ...) Vocabulary & Terminology Mapping Services (ICD-9/10 SNOMED, IMO, caDSR, ...)
Research Administration
Systems
Common Identifier Services (Patient, Provider, Research, Specimens, External Mappings) HIPAA/IRB Services (Honest Broker, De-ID Consent Management, …)
Epic Clarity
Patient Care Systems Epic
Centricity Documentation
Radiology
Pathology Pharmacy
CareLink/ Eclipsys
Others…
Scheduling
Revenue Cycle
Emergency Med.
Ambulatory
Research Core Facilities/‘Omics’
International Data Sharing with External Collaborators
CTSAs caBIG TCGA
Epic EHR Legacy +
ULAM
Tissue Biorepositories
Metabolomics
Proteomics
Bioinformatics
Next-Gen Sequencing
Bioinformatics and Systems Biology Workbenches
Collexis
eThority (billing)
Click Commerce
(IRB)
Research Pre, Post- Award
Industry: Pharma/ Biotech I2b2/
SHRINE
Others …
Demographics
Diseases
Individuals
Populations
Portals / Providers, Payors, P. Health D
atabases / HIEs / N
HIN
IT S
ERC
UIR
TY
Cam
pus
Syst
ems
IT Security
HSDW
i2b2
High Performance
Cloud Computing & Data Storage
IT S
ecur
ity
• Reporting • Visualization • Analysis & • Data Mining
IT Security
Research & Quality Metrics
Data Marts
Brian Athey & ECRIT 1/11/11
Health Sciences Library
Resources
NIH-Specific & External Data
Resources (PubMed, GenBank,
KEGG, GO, etc.)
SPORES
Others
CIDSS Analytics
& Reporting Tools
Quality Metrics
Reporting &
Peer Review
Education
CAD CDR Education
Knowledge Repository
Research Administration
Data Warehouse HIM
Others…
M-Pathways
CTools/Sakai 3
Curriculum Evaluation System
Clinical Scheduling
Comprehensive Clinical Assessment
Exam
Admissions
UMHS Data Architecture Unifying the Three Missions: Education, Research, & Patient Care
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Supporting Academic Health Centers is beyond ‘just Epic’ : Translational Biomedical Knowledge Creation & tranSMART
Gender Ethnicity Age Weight Diagnosis Medical History
Literature Databases Terminologies Ontologies
Lab Tests Genes Proteins
Biological Models Technologies Algorithms
Research
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Conceptual Vision: Building a Knowledge Network “Towards Precision Medicine”, Institute of Medicine (IOM); 2011, NAS.org.
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Lee Hood IOM February 27, 2012
The Science in the Middle: Linking models and driving problems to measurement core facilities, enabled by tranSMART
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Platform Development Collaboration
Pienta / Athey
Collaboration
Brady Urological Institute
Other Johns Hopkins
Units
• 3-D Imaging Cell Lines • 3-D Tissue Imaging • Genomics, Epigenomics • Proteomics • Metabolomics • Data and Metadata
concerning studies
• Bio-specimen Repositories • Next Generation Sequencing Core • Morphology Core • Specified links to CRM and
EHR resources
• Oncology Dept. • Cancer Center • Others
• Broader enablement of Personalized Medicine
tranSMART | JHU | Scaling to Johns Hopkins Medicine
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Theory
Mathematical Modeling
Modeling
Preclinical Studies
Preclinical therapeutics
Clinical studies Bi
oinf
orm
atic
s/tr
anSM
ART
Trans-Brady Datamart/tranSMART
Pienta lab: The etiology of cancer cell dormancy in the cancer ecosystem
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Stem? Modeling Dormancy
‘omics
EMT-MET
Bioi
nfor
mat
ics/
tran
SMAR
T
Trans-Brady Datamart/tranSMART
2DCell morphology CD44 RBM3
3D Cytoskeleton
Metabolism
RCI OVO-ZEB
In vivo Dispersion studies
anti-CXCR4
Pienta lab: The etiology of cancer cell dormancy
Clinical studies
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tranSMART | JHU | The Brady
• Datasets to be harmonized and loaded into tranSMART (patients & samples including biorepositories) – Primary prostatectomy (>10,000) – Active surveillance (>1000) – Familial genetics (>1000) – Radiation Oncology (>5000) – Advanced prostate cancer (>100) – Kidney cancer (>100) – Bladder cancer (>100) – Pediatric bladder extrophy (>500)
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Presentation Outline
• tranSMART – Brief History / Current Use/Demo • tranSMART at Johns Hopkins University
– Scope of Pienta-Athey Lab Collaborative Demonstration Project (EPI-EMT Transformation in PCa)
– National Center for Integrative Biomedical Informatics (NCIBI) Tools, PerkinElmer (PE) Spotfire
– Establishing and Harmonizing databases across The Brady Institute
– Currently: Evaluating PE or IDBS Electronic Laboratory Notebook (ELN)
– Future: Scaling more broadly to Johns Hopkins Medicine • tranSMART at University of Michigan
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tranSMART | JHU | Pienta-Athey Lab Project
• Platform Development of 3D Microscopic Imaging Technologies, Analytical Pipelines, and Data and Information Reporting Services – Integrative characterization of the cell phenotypes
involved in metastasis – Re-engineering image processing pipeline
• Accommodate fluorescence Interphase FISH • Tissue imaging replacing Feulgen with DAPI or other
appropriate DNA staining
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Fundamental Microscopy Data Types
• Nuclear Morphometry • Nuclear size • Nuclear circularity and shape parameters • DNA content via integrated fluorescent signal
• Chromosome Territories • Position, shape, volume
• Sub-territory bodies (loci, collections of loci, chromosomal segments e.g. TDs) • Position, shape, volume
• Immunofluorescence of , e.g., epigenetic histone marks • Localization to CTs, sub-territory bodies, morphometric nuclear
regions
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TMPRSS-ERG Fluorescence Micrograph
• Bracken, H, et al, Association of SPINK1 Expression and TMPRSS2:ERG Fusion with Prognosis in Endocrine-Treated Prostate Cancer. Clin. Cancer Res., 2010
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Dataset Explorer – Images (prototype) 2
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Athey Imaging Pipeline Service to tranSMART Platform
Raw Cn Raw C…
Experiment Cells, Prep, Features, Channels
Microscope Setup/Image
Full Image Metadata & DB
1K x 1K x Z x C Grid Images
QC
C0 Nucleus Bounding Box
Nucleus BB
Raw C1 Raw C0
Voxels and Clusters For each BB Voxel list file: x,y,z,v0, … vn Image file: for each color Stats: Min, Max, Stdev Threshold: intensity and size For each BB color cluster Voxel list file: x,y,z,v Voxels: count, centroid Threshold: intensity and size
Chromosome Territories
Tissue/Nuclear Morphometry
Immuno-fluor
Outputs to tranSMART
Spectral Unmixing …
Locus-specific
Metadata for above
1K x 1K x Z x C Grid Images
Electronic Lab
Notebook
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tranSMART | JHU | Leveraging Global Initiatives
• NIH National Center for Integrative Biomedical Informatics (NCIBI); Michigan-based – Bioinformatics, Systems Biology Network Analysis,
Reference Data
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NIH National Center for Integrative Biomedical Informatics (NCIBI) integration with tranSMART
Tools Data
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NCIBI in tranSMART
The user can find Medical Subject Headings (MeSH terms) enriched for a particular compound with links to the supporting PubMed publications.
Metab2MeSH Gene2MeSH
The user can find Medical Subject Headings (MeSH terms) enriched for a particular gene with links to the supporting PubMed publications.
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NCIBI in tranSMART
The user can visualize the interactions of genes, enzymes, reactions and compounds in human metabolomics pathways.
Metscape ConceptGen
The user can find biomedical concepts (pathways, MeSH terms, GO terms) enriched for a list of genes or associations between concepts based on overlapping gene sets.
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Demo Screenshots
Terry Weymouth Tuesday, Nov 5, 2013
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Demo Site Login
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Dataset Explorer - Overview
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Dataset Explorer – Summary Statistics
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Dataset Explorer – Images (prototype) 1
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Dataset Explorer – Hierarchical Clustering 1
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Dataset Explorer – Hierarchical Clustering 2
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Gene List Panel
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NCIBI - Pubmed
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NCIBI – Concept Explorer (ConceptGen)
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NCIBI - Pubmed
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NCIBI – Compound Network (MetScape)
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NCIBI – Gene2Mesh
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NCIBI – Metab2Mesh
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Spotfire @ Michigan w/tranSMART
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tranSMART Architecture – where Spotfire fits
Option 1 – as a Core Application with Information Links to the underlying Data Stores
Source: Stuart D, Harju J, Shi W, Hanauer D, Aronzon D, Liu J, Sharma R, Manion F, Xia H, Hutter C, Gruber S. tranSMART Supports a Post-GWAS Data Coordinating Center. American Medical Informatics Association Annual Symposium, Chicago IL, November 4-7, 2012.
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tranSMART Architecture – where Spotfire fits
Option 2 – as a Scientific Analysis Tool with capability to consume output from the Core Applications
Source: Stuart D, Harju J, Shi W, Hanauer D, Aronzon D, Liu J, Sharma R, Manion F, Xia H, Hutter C, Gruber S. tranSMART Supports a Post-GWAS Data Coordinating Center. American Medical Informatics Association Annual Symposium, Chicago IL, November 4-7, 2012.
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Spotfire: Translational Data – Novel GEA analysis
Kruskal-Wallis test of all significantly
differentially expressed probes
vs. all clincal response criteria
Overlay binned gene expression
levels on time-on-trial plot
Embedded links out to Entrez, Uniprot,
etc.
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Spotfire: Translational Data – Merge NGS and GEA
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Platform Development Collaborations
Athey/ Burant
Collaboration
MRC2 NIH Regional
Metabolomics Center
Others
• Genomics, Epigenomics • Proteomics • Metabolomics • Data and Metadata
concerning phenotypic studies in investigational weight management clinic
• NIH National Metabolomics DCC @ SDSC
• Bio-specimen Repositories • Next Generation Sequencing Core • Nutrition Core • Specified links to CRM and
EHR resources
• Nephology • Cancer Center • Research IT • Others schools and colleges
• Broader enablement of Personalized Medicine
tranSMART | UM | Scaling to U-Michigan Medicine
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Thank you/Questions/Discussion
Quiz: Which one is which?