Disease gene identification by random walk on multigraphs merging heterogeneous genomic and phenotype data

BMC Genomics

Proceedings

Jinyan Li¹  Yongjin Li² 

[1] Advanced Analytics Institute, Faculty of Engineering and IT, University of Technology, Sydney, Australia;Center for Systems Biology, University of Texas at Dallas, USA;

关键词: Disease Gene;    Rank List;    Human Protein Reference Database;    Random Walk With Restart;    Single Data Source;   

DOI  :  10.1186/1471-2164-13-S7-S27

来源: Springer

【 摘 要 】

BackgroundHigh 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.ResultsIn 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.ConclusionsThe proposed RWRM (Random Walk with Restart on Multigraphs) model and CHN (Complex Heterogeneous Network) model are effective in data integration for candidate gene prioritization.

【 授权许可】

CC BY   
© Li et al.; licensee BioMed Central Ltd. 2012