transmart - i2b2 · clinical trials, clinical and pre-clinical gene expression, protein profiling...
TRANSCRIPT
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December 2010
tranSMART
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Aim
� Focus - Translational Research
� Sampling of questions to be answered – what is the correlation between animal models and
human data? – what is the best biomarker strategy for a given
compound ? – what is the best indication for a given compound? – how can a disease stratified based on clinical data? – is there support for a target of interest based on
clinical data?
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Precompetitive Sharing
Ubiquitous Access
Ø Indication selection Ø Target/pathway hypothesis Ø Biomarker hypothesis Ø Clinical study design
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Academic Partnerships
� Based on i2b2 release 1.3 � GDE Consortium is being formed
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Infrastructure
� Amazon Elastic Compute Cloud – Security – Cost – Scalability – HPC – Amazon data feeds
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Fine-grained Security Model � Strong authentication
� Strong governance – study owners, established process – Training – Access granting process is established and followed – Clinical trial nodes grayed-out if no access is granted
Access Model
Sys
tem
Ow
ner
Stu
dy O
wne
r/B
iom
arke
r Rep
Adm
inis
trato
rR
eque
stor Submit request to
Administrator
Create usercredentials
Existing user?Communicatecredentials to
requestor
Does role needapproval?
Approve?
Assign appropriaterole
No
End
Yes
No
Verify credentialswork
Yes
No
Yes
Approve?
End End
Approve?
No
Yes
Yes
No
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Dictionaries, Ontologies and Master Data
� Gene/protein names and alternatives (Entrez) � Gene name mapping service (Affy ID, SNP, protein) � Pathways (GO, KEGG, GeneGo, Ingenuity, Ariadne,
MSigDB) � Internal signatures � Diseases (MeSH, ICD10) � Clinical trial observations (MedDRA) � J&J drugs dictionary � Clinical trials metadata dictionary � Cell line dictionary � Curated inhibitors (CAS id)
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Gather input from data owner
Communica3on with data steward to help iden3fy appropriate data
Data transfer
Obtains, reads and understands trial
Protocol and other relevant
documentation
Collects permissions and
actual data
Transforms into Dataset Explorer
format trough i2b2 protocols &
load
Identify most relevant data
com
mun
icat
ion
Data transfer
Classifies data according to
established schema and converts data
to SAS format
QA and QC Deploy
Curation Process for Internal Trials
Confidential
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Big Scary Diagram
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tranSMART Data Warehouse
� Data – Structured Data
� Clinical trials, clinical and pre-clinical gene expression, protein profiling (RBM), SNP, PD markers, metabolomics, proteomics
– In-house – immunology (large and small mol), oncology, psychiatry – Public and commercial
– Unstructured Data � Curated text � Text indexing
– Master data, ontologies, vocabularies and metadata – Federated sources
� User Interfaces – Search
� Gene, pathway, disease, compound, trial, and combinations – Hypothesis testing
� Cohort selection and comparison/analysis – Hypothesis generation
� Gene signatures – Analytics workflows
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Statistics
� Dataset Explorer – 42 internal studies (clinical trials, experimental medicine
studies, in vivo and ex vivo experiments) – 43 public studies – Oncology, immunology, cardiovascular, CNS
� Search – 10 internal studies – 9,000 GEO/Array Express comparisons – 97 DFCI curated studies – 100,000 curated biomarker assertions
Confidential
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Platforms and Sources Roadmap
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Use Cases
� Knowledge Management/Search
� Hypothesis Testing
� Hypothesis Generation
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Search
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Curated Content in Semantic Networks
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Hypothesis Testing – Flexible Queries
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Hypothesis Testing – Simple Statistics
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Hypothesis Testing – Advanced Statistics
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Advanced Biomarker Analysis
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Meta-analysis
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Cross-Study Queries
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Indication Hypothesis Generation � Disease Profiles Database
– Well curated – Well annotated – QCd
� Database of 9,000 public comparisons from NCBI GEO and EBI Array Express
� Subset is molecular profiles of disease vs. normal samples – Also, proprietary data!
� Drug or Pathway Modulation Signatures – In vitro, in vivo or clinical samples – Treatment vs. placebo or before vs. after or …
� Drug, siRNA, Ab, KO, … – Measure gene expression, protein expression, … – Statistical analysis and derivation of statistically significant
list of genes (proteins, …) with direction
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Indication Hypothesis Generation
in vitro ex vivo in vivo
Manuscript in preparation.
TEA in tranSMART
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Implemented Disruptive Technology
� Open source
� Cloud computing
� Pre-competitive sharing
� Informatics/IT
� Recombinant Data
� Business partners across multiple TAs (Biology, Biomarkers, Translational Medicine, Clinical)
� Academic partners
Confidential