Mike Barnes, William Harvey Research Institute, QMUL on the MRC Stratified Medicine TranSMARTs

1. MRC Stratified Medicine
TranSMARTs
Mike Barnes
William Harvey Research Institute
QMUL
m.r.barnes@qmul.ac.uk 28/4/2015

2. Genomics: A Systems Approach
Drug
Endotypes
Disease
Endotypes
Molecular
Mechanisms
TNFR1
Novel
Mechanistic
InsightsApoptosis
Inflammation
Omic
(RNA, protein)
Drug Response
(Connectivity Map)
TNF
JNK1
NFKB
CD20
Infliximab
RituximabmabTocilizumabTNF signalling
Cytokine signalling
Genetic
Synovium
Blood

3. TranSMART: MRC Stratified Medicine
RA-MAP
MATURA
Rheumatoid Arthritis Psoriasis
Biologic response biomarkersDisease biomarkers

4. PSORTData
Generation
Pharma
TranSMARTs
MATURA
TranSMART
TranslationalMedicine
Platform
RA-Map TranSMART
Portal
Extraction Layer – Standardize extracted data formats
Semantic normalisation
Compliant,Auditable&
Traceable
CatalogofOntology&
Terminology
Data Checking & Validation
Pseudo-anonymisation Platform
Cohort Selection
and Biostatistics
Omics Analysis /
Bioinformatics
Biomarker
Discovery
NormalisedDataSharing
PSORT
TranSMART
Clinical Cohort
Phenotypic Data
Demographics
Clinical observations
Clinical trail outcomes
Adverse events
Reference Data
Literature
Pathway data
Gene metadata
Drug data
High content
biomarker data
Gene Expression
Genotypes
Metabolomics
PK/PD markers
Future
TranSMARTs
firewalledvirtualmachines
MRC TranSMART data Infrastructure

5. TranSMART Data Content
PSORT
• Clinical, BADBIR, Clinical Trial
• Transcriptomic (mRNA,miRNA), Genetics, metabolomic
MATURA
• Clinical, Clinical Trial
• Genetics, Transcriptomics (mRNA, miRNA)
RA-MAP
• Clinical
• Transcriptomics (mRNA, miRNA)

6. MRC Stratified Medicine:
Security and Data Sharing Models
“Controlled Data hub”
• Data can be downloaded
 Fully audit trail
• Analysis at partner sites
• Background data by CDA
Pros
• Available now
• More agile analysis
• Simpler admin
• Analyst freedom locally
Cons
• Less secure
“Analysis safe haven”
• Data cannot be downloaded
• All analysis on safe haven
Pros
• Secure
Cons
• Complex server admin
• Less flexible analysis
• VM access can be slow
• Solution not available yet
• Resource intensive (high cost)
Open ClosedShared Principles
• Standardised, versioned data
• Access based on contribution “give more, get more”
• Access control by data set

7. PSORT/RAMAP Controlled Data Hub
TranSMART
Data QC
Secure Data
Sharing
Data
Standardisation
Data Integration
Data Export
Simple data
analysis
Analysis on Data Exports using local
Compute resources
• R statistical analysis etc
• Machine Learning
• GWAS
• High-dimensional
• High Performance computing
pipelined
analysis (plugins)
R backend

8. MATURA “Analysis Safe Haven”
Analysis on Data Exports using
Elastic compute resources on VM
• Standardised reference data sets
• R statistical analysis etc
• Machine Learning
• GWAS
• High-dimensional analysis
• High Performance computing
Data
Exports
MATURA
CMB Approval
Public
Data
Analysis VM

9. MRC Stratified Medicine:
Infrastructure Evolution
MRC
eMEDLAB
VM
hosting
•Central data centre
•Open Stack Architecture
•TranSMART hosting
•Secure data access
•Elastic compute for all analysis
Sept2015Now
•QMUL data centre
•TranSMART hosting
•Secure data access
•Limited analysis

10. RA-MAP - TranSMART

11. Acknowledgements
QMUL
Richard Christie
Simon Butcher
Oliver Greenaway
eTRIKS
Anthony Rowe (J&J)
Yike Guo
Ioannis Pandis
Wei Gu
Denny Verbeeck
Francisco Capdevila