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

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

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

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

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

Conceptual Vision: Building a Knowledge Network “Towards Precision Medicine”, Institute of Medicine (IOM); 2011, NAS.org.

Lee Hood IOM February 27, 2012

The Science in the Middle: Linking models and driving problems to measurement core facilities, enabled by tranSMART

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

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

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

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)

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

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

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

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

Dataset Explorer – Images (prototype) 2

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

tranSMART | JHU | Leveraging Global Initiatives

• NIH National Center for Integrative Biomedical Informatics (NCIBI); Michigan-based – Bioinformatics, Systems Biology Network Analysis,

Reference Data

NIH National Center for Integrative Biomedical Informatics (NCIBI) integration with tranSMART

Tools Data

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.

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.

Demo Screenshots

Terry Weymouth Tuesday, Nov 5, 2013

Demo Site Login

Dataset Explorer - Overview

Dataset Explorer – Summary Statistics

Dataset Explorer – Images (prototype) 1

Dataset Explorer – Hierarchical Clustering 1

Dataset Explorer – Hierarchical Clustering 2

Gene List Panel

NCIBI - Pubmed

NCIBI – Concept Explorer (ConceptGen)

NCIBI - Pubmed

NCIBI – Compound Network (MetScape)

NCIBI – Gene2Mesh

NCIBI – Metab2Mesh

Spotfire @ Michigan w/tranSMART

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.

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.

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.

Spotfire: Translational Data – Merge NGS and GEA

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

Thank you/Questions/Discussion

Quiz: Which one is which?