title: Detection of candidate tumor driver genes using a fully integrated Bayesian approach.
abstract: DNA copy number alterations (CNAs), including amplifications and deletions, can result in significant changes in gene expression and are closely related to the development and progression of many diseases, especially cancer. For example, CNA-associated expression changes in certain genes (called candidate tumor driver genes) can alter the expression levels of many downstream genes through transcription regulation and cause cancer. Identification of such candidate tumor driver genes leads to discovery of novel therapeutic targets for personalized treatment of cancers. Several approaches have been developed for this purpose by using both copy number and gene expression data. In this study, we propose a Bayesian approach to identify candidate tumor driver genes, in which the copy number and gene expression data are modeled together, and the dependency between the two data types is modeled through conditional probabilities. The proposed joint modeling approach can identify CNA and differentially expressed genes simultaneously, leading to improved detection of candidate tumor driver genes and comprehensive understanding of underlying biological processes. We evaluated the proposed method in simulation studies, and then applied to a head and neck squamous cell carcinoma data set. Both simulation studies and data application show that the joint modeling approach can significantly improve the performance in identifying candidate tumor driver genes, when compared with other existing approaches.
authors.affiliation: Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, U.S.A.
authors.forename: Jichen
authors.initials: J
authors.lastname: Yang
authors.forename: Xinlei
authors.initials: X
authors.lastname: Wang
authors.forename: Minsoo
authors.initials: M
authors.lastname: Kim
authors.forename: Yang
authors.initials: Y
authors.lastname: Xie
authors.forename: Guanghua
authors.initials: G
authors.lastname: Xiao
mesh_terms: D001499:Bayes Theorem; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D003198:Computer Simulation; D018628:Gene Dosage / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics; D006801:Humans; D015233:Models, Statistical; D009369:Neoplasms / Q000235:genetics*
keywords: Bayesian joint modeling; hidden Markov model; integrative analysis