Skip Navigation



Bioinformatics Advance Access published online on April 5, 2009
Bioinformatics, doi:10.1093/bioinformatics/btp158
This Article
Right arrow Advance Access manuscript (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
25/10/1314    most recent
btp158v1
Right arrow Comments: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Comments are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Tsoi, L. C.
Right arrow Articles by Zheng, W. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tsoi, L. C.
Right arrow Articles by Zheng, W. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author (2009). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Evaluation of genome-wide association study results through development of ontology fingerprint

Lam C. Tsoi 1, Michael Boehnke 2, Richard L. Klein 3,4 and W. Jim Zheng 5,*

1 Bioinformatics Graduate Program, Department of Biostatistics, Bioinformatics and Epidemiology, Medical University of South Carolina, Charleston, SC.
2 Department of Biostatistics and Center for Statistical Genetics, School of Public Health, University of Michigan, Ann Arbor, MI
3 Division of Endocrinology, Metabolism, and Medical Genetics, Department of Medicine, Medical University of South Carolina
4 Research Service, Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC
5 Department of Biostatistics, Bioinformatics & Epidemiology, Medical University of South Carolina, Charleston, SC

*To whom correspondence should be addressed. W. Jim Zheng, E-mail: zhengw{at}musc.edu


  Abstract

Motivation: Genome-wide association (GWA) studies may identify multiple variants that are associated with a disease or trait. To narrow down candidates for further validation, quantitatively assessing how identified genes relate to a phenotype of interest is important.

Results: We describe an approach to characterize genes or biological concepts (phenotypes, pathways, diseases, etc) by ontology fingerprint—the set of Gene Ontology terms that are overrepresented among the PubMed abstracts discussing the gene or biological concept together with the enrichment p-value of these terms generated from a hypergeometric enrichment test. We then quantify the relevance of genes to the trait from a GWA study by calculating similarity scores between their ontology fingerprints using enrichment p-values. We validate this approach by correctly identifying corresponding genes for biological pathways with a ninety percent average area under the ROC curve (AUC). We applied this approach to rank genes identified through a GWA study that are associated with the lipid concentrations in plasma as well as to prioritize genes within linkage disequilibrium (LD) block. We found that the genes with highest scores were: ABCA1, LPL, and CETP for HDL; LDLR, APOE and APOB for LDL; and LPL, APOA1 and APOB for triglyceride. In addition, we identified genes relevant to lipid metabolism from the literature even in cases where such knowledge was not reflected in current annotation of these genes. These results demonstrate that ontology fingerprints can be used effectively to prioritize genes from GWA studies for experimental validation.

Associate Editor: Prof. John Quackenbush

Received on January 8, 2009; revised on February 25, 2009; accepted on March 14, 2009

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.