Incorporation of Genetic Pathway Information into Analysis of Multivariate Gene Expression Data

Abstract: Multivariate microarray gene expression data are commonly collected to study the genomic responses under ordered conditions such as over increasing/decreasing dose levels or over time during biological processes. One important question from such multivariate gene expression experiments is to identify genes that show different expression patterns over treatment dosages or over time and pathways that are perturbed during a given biological process. In this paper, we develop a hidden Markov random field model for multivariate expression data in order to identify genes and subnetworks that are related to biological processes, where the dependency of the differential expression patterns of genes on the networks are modeled by a Markov random field. Simulation studies indicated that the method is quite effective in identifying genes and the modified subnetworks and has higher sensitivity than the commonly used procedures that do not use the pathway information, with similar observed false discovery rates. We applied the proposed methods for analysis of a microarray time course gene expression study of TrkA- and TrkB-transfected neuroblastoma cell lines and identified genes and subnetworks on MAPK, focal adhesion and prion disease pathways that may explain cell differentiation in TrkA-transfected cell lines