Walking on multiple disease-gene networks to prioritize candidate genes

作     者：Rui Jiang 

作者机构：MOE Key Laboratory of BioinformaticsDivision and Center for Synthetic&Systems BiologyTNLISTDepartment of AutomationTsinghua UniversityBeijing 100084China Department of StatisticsStanford UniversityStanfordCA 94305USA 

出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)

年 卷 期：2015年第7卷第3期

页      面：214-230页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：This work was supported by the National Basic Research Program of China(2012CB316504) the National High Technology Research and Development Program of China(2012AA020401) the National Natural Science Foundation of China(61175002) 

主　　题：disease-gene network gene prioritization random walk data fusion 

摘      要：Uncovering causal genes for human inherited diseases,as the primary step toward understanding the pathogenesis of these diseases,requires a combined analysis of genetic and genomic *** bioinformatics methods have been designed to prioritize candidate genes resulting fromgenetic linkage analysis or association studies,the coverage of both diseases and genes in existing methods is quite limited,thereby preventing the scan of causal genes for a significant proportion of diseases at the whole-genome *** overcome this limitation,we propose a method named pgWalk to prioritize candidate genes by integrating multiple phenomic and genomic *** derive three types of phenotype similarities among 7719 diseases and nine types of functional similarities among 20327 *** on a pair of phenotype and gene similarities,we construct a disease-gene network and then simulate the process that a random walker wanders on such a heterogeneous network to quantify the strength of association between a candidate gene and a query disease.A weighted version of the Fisher’s method with dependent correction is adopted to integrate 27 scores obtained in this way,and a final q-value is calibrated for prioritizing candidate genes.A series of validation experiments are conducted to demonstrate the superior performance of this *** further show the effectiveness of this method in exome sequencing studies of autism and epileptic *** online service and the standalone software of pgWalk can be found at http://***/jianglab/pgwalk.