Disease Gene Identification by Random Walk on Multigraphs Merging Heterogeneous Genomic and Phenotype Data

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Abstract

BACKGROUND: High throughput experiments resulted in many genomic datasets and hundreds of candidate disease genes. To discover the real disease genes from a set of candidate genes, computational methods have been proposed and worked on various types of genomic data sources. As a single source of genomic data is prone of bias, incompleteness and noise, integration of different genomic data sources is highly demanded to accomplish reliable disease gene identification. RESULTS: In contrast to the commonly adapted data integration approach which integrates separate lists of candidate genes derived from the each single data sources, we merge various genomic networks into a multigraph which is capable of connecting multiple edges between a pair of nodes. This novel approach provides a data platform with strong noise tolerance to prioritize the disease genes. A new idea of random walk is then developed to work on multigraphs using a modified step to calculate the transition matrix. Our method is further enhanced to deal with heterogeneous data types by allowing cross-walk between phenotype and gene networks. Compared on benchmark datasets, our method is shown to be more accurate than the state-of-the-art methods in disease gene identification. We also conducted a case study to identify disease genes for Insulin-Dependent Diabetes Mellitus. Some of the newly identified disease genes are supported by recently published literature. CONCLUSIONS: The proposed RWRM (Random Walk with Restart on Multigraphs) model and CHN (Complex Heterogeneous Network) model are effective in data integration for candidate gene prioritization.

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"From Asia Pacific Bioinformatics Network (APBioNet) Eleventh International Conference on Bioinformatics (InCoB2012) Bangkok, Thailand. 3-5 October 2012"
Keywords
Genomics, Diabetes, Genetic algorithms
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CC BY 2.0 (Attribution), ©2012 Li, et al.
Citation
Li, Yongjin, and Jinyan Li. 2012. "Disease gene identification by random walk on multigraphs merging heterogeneous genomic and phenotype data.." BMC Genomics 13 Suppl 7: S27.