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PMID: 19465376 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

ToppGene Suite for gene list enrichment analysis and candidate gene prioritization.

Nucleic acids research ·Vol. 37 ·No. Web Server issue ·2009-07-00 ·Pages W305-11

Chen J, Bardes EE, Aronow BJ, Jegga AG

Abstract

ToppGene Suite (http://toppgene.cchmc.org; this web site is free and open to all users and does not require a login to access) is a one-stop portal for (i) gene list functional enrichment, (ii) candidate gene prioritization using either functional annotations or network analysis and (iii) identification and prioritization of novel disease candidate genes in the interactome. Functional annotation-based disease candidate gene prioritization uses a fuzzy-based similarity measure to compute the similarity between any two genes based on semantic annotations. The similarity scores from individual features are combined into an overall score using statistical meta-analysis. A P-value of each annotation of a test gene is derived by random sampling of the whole genome. The protein-protein interaction network (PPIN)-based disease candidate gene prioritization uses social and Web networks analysis algorithms (extended versions of the PageRank and HITS algorithms, and the K-Step Markov method). We demonstrate the utility of ToppGene Suite using 20 recently reported GWAS-based gene-disease associations (including novel disease genes) representing five diseases. ToppGene ranked 19 of 20 (95%) candidate genes within the top 20%, while ToppNet ranked 12 of 16 (75%) candidate genes among the top 20%.

MeSH Terms
Animals Disease/genetics Genes Humans Internet Mice Protein Interaction Mapping Proteins/genetics Software
Chemicals
Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Chen Jing
Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA.
Bardes Eric E
Aronow Bruce J
Jegga Anil G
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkp427
Published
2009-07-00
Epub
2009-00-22
Pages
W305-11
Language
English
Region
England
NLM ID
0411011
PMCID
PMC2703978
Subset
IM
Grants
NIDDK NIH HHS · 1U01 DK70219 · United States
NIDDK NIH HHS · P30 DK078392 · United States
External Links
PubMed source DOI: 10.1093/nar/gkp427 PMC Full Text View journal details
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