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Bioinformatics Advance Access published online on November 24, 2008
Bioinformatics, doi:10.1093/bioinformatics/btn613
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© The Author (2008). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Prioritizing Risk Pathways: A Novel Association Approach to Searching for Disease Pathways Fusing SNPs and Pathways

Lina Chen 1,*, Liangcai Zhang 1, Yan Zhao 1, Liangde Xu 1, Yukui Shang 1, Qian Wang 1, Wan Li 1, Hong Wang 1 and Xia Li 1,*

1College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

*To whom correspondence should be addressed. Prof. Lina Chen, E-mail: chenlina{at}ems.hrbmu.edu.cn, Xia Li, E-mail: lixia{at}hrbmu.edu.cn


  Abstract

Motivation: Complex diseases are generally thought to be under the influence of one or more mutated risk genes as well as genetic and environmental factors. Many traditional methods have been developed to identify susceptibility genes assuming a single-gene disease model ("single-locus methods"). Pathway-based approaches, combined with traditional methods, consider the joint effects of genetic factor and biologic network context. With the accumulation of high-throughput SNP datasets and human biologic pathways, it becomes feasible to search for risk pathways associated with complex diseases using bioinformatics methods. By analyzing the contribution of genetic factor and biologic network context in KEGG pathways, we proposed an approach to prioritize risk pathways for complex diseases: Prioritizing Risk Pathways fusing SNPs and pathways (PRP). A risk-scoring (RS) measurement was used to prioritize risk biologic pathways. This could help to demonstrate the pathogenesis of complex diseases from a new perspective and provide new hypotheses. We introduced this approach to five complex diseases and found that these five diseases not only share common risk pathways, but also have their specific risk pathways, which is verified by literature retrieval.

Associate Editor: Dr. Alex Bateman

Received on August 1, 2008; revised on October 27, 2008; accepted on November 21, 2008

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