The knowledge-driven exploration of integrated biomedical knowledge sources facilitates the...
-
Upload
knoesis-center-wright-state-university -
Category
Technology
-
view
2.242 -
download
1
description
Transcript of The knowledge-driven exploration of integrated biomedical knowledge sources facilitates the...
The knowledge-driven exploration of integrated
biomedical knowledge sources facilitates the
generation of new hypotheses
Vinh Nguyen, Olivier Bodenreider, Todd Mining, AmitSheth
Context
• Chagas disease
– Infectious disease caused by Trypanosomacruzi(T. cruzi) parasite
– Affects 8-10 million people in South America, about 20,000 deaths per year
– Finding drug targets and vaccine
210/21/2011
Context
310/21/2011
Why integrate two?
• Synergistically exploit the two sources
– If literature indicates certain finding (for the same or other organism [mice, rat], for same or different process [e.g. for gene expression], does my data support the same finding?
– I find a pattern in my data, or a pathway component – is this reported in literature by someone in the same or similar context?
10/21/2011 4
10/21/2011 5
The knowledge-driven integrated exploitation of complementary sources, which can facilitate generation of new hypotheses for additional investigations and insights.
Use case
• Data sources
– Text data from PubMed
– Experimental data about Chagas disease
• Objectives/capabilities
– Query experimental and literature (text) together
– Find new insights into Chagas disease
610/21/2011
Background Knowledge
• Two knowledge bases were linked/partly integrated– The Biomedical Knowledge Repository (BKR) [NLM]
– The Parasite Knowledge Repository for Chagas disease (PKR)
710/21/2011
Knowledge source - BKR
• Created at NLM by Dr. Olivier Bodenreider and Dr. Thomas Rindflesch
• ~ 20 million predications from 6 million PubMed articles by SemRep
• Example
810/21/2011
Knowledge source - PKR
Created by T.cruziproject at Kno.e.sis, WSU with CTEGD, UGA primarily for semantic analysis of parasite experimental data from/including:
• The expression level of T. cruzi genes (from Microarray analysis data)
• The presence of proteins encoded by T. cruzi genes (using Proteome analysis)
• Ontologies for annotation– Parasite Experiment Ontology (PEO)– Parasite Lifecycle Ontology (PLO)
910/21/2011
Linking the two knowledge bases
• Orthology relation
– Gene function is usually conserved across species
1010/21/2011
How to explore the integrated knowledge bases?
• Knowledge-driven exploration process
• Two steps of the process– Navigate the chain of named relationships
• Graph expansion• Graph restriction
– Interpret the chain to infer new hypothesis
1110/21/2011
Example of Exploration process• Sample chain
1210/21/2011
Exploration process – Demo
iExplorevideo demo is available at
http://www.youtube.com/watch?v=-7-BgBDTSjc
1310/21/2011
Exploration process -Interpretation
• Sample chain
1410/21/2011
The T. cruzi orthologs of human genes inhibited by itraconazole may also be inhibited by itraconazole and thus would be candidates for further studies into the mechanism(s) of action of the drug itraconazole on T. cruzi
-> Hypothesis
Significance
• Biologically
– Biologists follow the exploration process to generate novel hypotheses
– Can easily be generalized to other diseases
• Technically
– Technical details (e.g., SPARQL queries) hidden from the user
– Scalable over millions of predications
10/21/2011 15
Technologies
• Semantic Web
– RDF, SPARQL standards
– Virtuoso triple store
• iExplore development
– Client side: Flex application
– Server side: Java
10/21/2011 16
Conclusion• Integrate knowledge bases
– BKR
– PKR
• Knowledge-driven exploration
– Two-step process: navigation and interpretation
– Assist biologists to explore the integrated knowledge bases
1710/21/2011
Future work• Validation of novel hypotheses
– Collaborating with UGA researchers in the biomedical aspect
– Incorporate the validation into iExplore
• Automate the interpretation step
– Learning the way biologists use their background knowledge to interpret the chain of named relationship
1810/21/2011
Acknowledgements
Dr. Thomas Rindflesch
May Cheh
Dr. Clement McDonald
Dr. BastienRance
Jonathan Mortensen
John Nguyen
Thang Nguyen
Lister Hill Center
1910/21/2011
Dr. CarticRamakrishnan
Dr. Priti Parikh
Joshua Dotson
SarasiLalithsena
10/21/2011 20
10/21/2011 21
Further information, please visit http://knoesis.wright.edu/iExplore