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Bioinformatics Advance Access published online on November 13, 2008
Bioinformatics, doi:10.1093/bioinformatics/btn593
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© The Author (2008). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Align human interactome with phenome to identify causative genes and networks underlying disease families

Xuebing Wu , Qifang Liu and Rui Jiang *

MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST / Department of Automation, Tsinghua University, Beijing 100084, China

*To whom correspondence should be addressed. Rui Jiang, E-mail: ruijiang{at}tsinghua.edu.cn


  Abstract

Motivation: Understanding the complexity in gene-phenotype relationship is vital for revealing the genetic basis of common diseases. Recent studies on the basis of human interactome and phenome not only uncovers prevalent phenotypic overlap and genetic overlap between diseases, but also reveals a modular organization of the genetic landscape of human diseases, providing new opportunities to reduce the complexity in dissecting the gene-phenotype association.

Results: We provide systematic and quantitative evidence that phenotypic overlap implies genetic overlap. With these results, we perform the first heterogeneous alignment of human interactome and phenome via a network alignment technique, and identify 39 disease families with corresponding causative gene networks. Finally, we propose AlignPI, an alignment-based framework to predict disease genes, and identify plausible candidates for 70 diseases. Our method scales well to the whole genome, as demonstrated by prioritizing 6,154 genes across 37 chromosome regions for Crohn’ disease. Results are consistent with a recent meta-analysis of genome-wide association studies for Crohn's disease.

Availability: Bi-modules and disease gene predictions are freely available at the URL http://bioinfo.au.tsinghua.edu.cn/alignpi/

Contact: ruijiang{at}tsinghua.edu.cn

Supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: Dr. Trey Ideker

Received on July 16, 2008; revised on September 24, 2008; accepted on November 11, 2008

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