Network-based Phenome-Genome Association Prediction by Bi-Random Walk.
BACKGROUND
The availability of ontologies and systematic documentations of phenotypes and their genetic associations has enabled large-scale network-based global analyses of the association between the complete collection of phenotypes (phenome) and genes. To provide a fundamental understanding of how the network information is relevant to phenotype-gene associations, we analyze the circular bigraphs (CBGs) in OMIM human disease phenotype-gene association network and MGI mouse phentoype-gene association network, and introduce a bi-random walk (BiRW) algorithm to capture the CBG patterns in the networks for unveiling human and mouse phenome-genome association. BiRW performs separate random walk simultaneously on gene interaction network and phenotype similarity network to explore gene paths and phenotype paths in CBGs of different sizes to summarize their associations as predictions.


RESULTS
The analysis of both OMIM and MGI associations revealed that majority of the phenotype-gene associations are covered by CBG patterns of small path lengths, and there is a clear correlation between the CBG coverage and the predictability of the phenotype-gene associations. In the experiments on recovering known associations in cross-validations on human disease phenotypes and mouse phenotypes, BiRW effectively improved prediction performance over the compared methods. The constructed global human disease phenome-genome association map also revealed interesting new predictions and phenotype-gene modules by disease classes.
College of Software, Nankai University, Tianjin, China.
MaoQiang
M
Xie
College of Software, Nankai University, Tianjin, China.
YingJie
Y
Xu
College of Software, Nankai University, Tianjin, China.
YaoGong
Y
Zhang
Department of Clinical Science, University of Texas Southwestern Medical Center, Dallas, TX, USA.
TaeHyun
T
Hwang
Department of Computer Science and Engineering, University of Minnesota Twin Cities, Minneapolis, MN, USA.
Rui
R
Kuang
D000465:Algorithms; D000818:Animals; D019540:Area Under Curve; D005767:Gastrointestinal Diseases / Q000235:genetics; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies; D016678:Genome; D006801:Humans; D051379:Mice; D010641:Phenotype; D060066:Protein Interaction Maps