mcw department of physiology
DESCRIPTION
Accelerating Candidate Gene Discovery through Ontological Indexing of Large Scale Data Repositories Simon Twigger, Ph.D. MCW Department of Physiology. Human & Molecular Genetics Center. http://rgd.mcw.edu. Meet the client. Rat researchers ask. - PowerPoint PPT PresentationTRANSCRIPT
Accelerating Candidate Gene Discovery through Ontological Indexing of Large Scale Data Repositories
Simon Twigger, Ph.D.
MCW Department ofPhysiology
Human & Molecular Genetics Center
http://rgd.mcw.edu
Meet the client
Rat researchers ask...
What tissue is this gene expressed in?What expression data is known for SD (aka
SD/NHsd, Harlan Sprague Dawley,
Sprague Dawley) rats?
Are any of these genes associated
with my phenotype?Has this gene been seen in the brain?What rat expression studies have
been done on Mammary Cancer(aka breast neoplasms/breast
cancer/cancer of the breast, breast carcinoma...)?
Has anyone done any expression studies using congenic rats?
Biological Data Warehouse
Really important piece of data...
Problem...
WherWhere, e,
what,what,when?when?
+
(one) Solution?
WhereWhere, ,
what,what,when?when?
+
How to create the index?
Examine One by One?
Analysis of anterior pituitary glands of ACI, Copenhagen, and Brown Norway males following treatment with the synthetic estrogen diethylstilbestrol (DES).
Copenhagen = COPBrown Norway = BN
NCBO ontology services
http://bioportal.bioontology.org/annotator
Open Biomedical Annotator
http://www.bioontology.org/wiki/index.php/Annotator_Web_service
• Datasets
• Series• Sample
s
• Datasets
• Series• Sample
s
Initial Ontologies & Workflow
Phase 1Small Scale Testing
http://gminer.mcw.edu/
Initial Test Load:
30 Rat Dataset records (GDS) out of 23632 Series records (GSE) out of 750587 Sample records (GSM) out of 7288
RubyOnRails web application to view data
Parallel Annotation Workflow
Concurrent Annotation Results
August October
Cloud-enabled Workflow?
Results/Demo
Initial Observations - Synonyms
DES
Ept6Searching with synonyms can be great:Ept6 = ACI.COP-(D3Mgh16-D3Rat119)/ShulDES = Diethylystilbestrol
Initial Observations - Synonyms
Searching with synonyms can cause problems:Estrogen-induced pituitary tumorigenesis = EPTEthanolaminephosphotransferase activity = EPT
Initial Observations 2Rat Strain symbols
AT, AN, AS, A, B, CDG (1000 x g)C (˚C)TX (Abbreviation for Texas)
...pituitary gland of the ACI, Copenhagen and Brown Norway Rat.
...16 month-old Sprague-Dawley females that......expression data from female SD rats with access to
lifelong......Strain or Line: F344/NCrl ...
...dahl Salt-sensitive (S) rat and S.R(9)x3A congenic rat....
...kidneys from Dahl salt-sensitive males...
Train classifier on real strain phrases? Look for relevant neighboring terms?
Initial Observations - Anatomy
In GEO recordsIn GEO records Corresponding MA termCorresponding MA termWhite Adipose Tissue White FatBrown Adipose Tissue Brown Fat
Ulnar bone Ulna boneSkeletal Muscle Set of Skeletal Muscle
Anterior Pituitary Anterior Pituitary GlandCalvarial Bone ChondrocraniumLeft Ventricle Heart Left Ventricle
Potential synonyms that could be added to MA
Phase 2All Rat Affy Samples
1 ontology (Anatomy)
0 Rat Dataset records (GDS)479 Series records (GSE)12,012 Sample records (GSM)
Larger scale data load
Targeted Indexing
Mouse AdultGross Anatomy
Ontology
Results/Demo
Linking annotations to data
Tm2d1
RGD1306410
Svs4
Hbb
Scgb2a1
Alb
Tm2d1
RGD1306410
Svs4
HbbScgb2a
1Alb
+
Hbb is_expressed_in rat kidneyTm2d1 is_expressed_in rat kidney
Human (U133, U133v2.), Mouse (430, U74, U95) and Rat (U34a/b/c, 230, 230v2)62,000 samples x ca. 25,000 genes/sample = 1.5B data points
Linking annotations to data
Probeset results on GMiner
Gabdr
Probeset results on GMiner
RDF Data integration
Triple StoreTriple Store
OpenRDF Sesame
Virtuoso Open Source
Rat Genes& xrefs
Probeset toRGD ID
Probesetto MA
Mouse AnatomyOntology
Ongoing•Work on term recognition, strains, etc.
•Evaluation of Probeset-to-Anatomy results
•Curation interface to add additional terms
•RDF formats, Triple Store implementation
•Integrate Strain and tissue results into RGD
Education & Outreach
Meet the student
You!
Heavy ScientificProblem
Ontologies More knowledge
through
education =
bigger lever!
Researchers
Video #3 is being shot this week
Future Videos
Target is the scientist!
• Solve common tasks• Use annotation tools• Evaluate annotations
• Intro to specific ontologies• Interview ontology teams
• Ideas?• What does your community need?
Acknowledgements
• Joey Geiger - Development of GMiner
• Jennifer Smith - Video creation, data curation
• Rajni Nigam - Rat Strain Ontology
• Clement Jonquet - NCBO OBA tools
• Trish Whetzel - Video script feedback
• Mark Musen & NIH Roadmap Initiative - Our Funding!
Links
• http://twigger.hmgc.mcw.edu/ncbo/ Project webpage
• http://gminer.mcw.edu Web application
• http://github.com/mcwbbc/gminer Gminer Code
• http://github.com/simont/MCW-RDF RDFizer code