title: Random Effects Model for Multiple Pathway Analysis with Applications to Type II Diabetes Microarray Data.
abstract: Close to three percent of the world's population suffer from diabetes. Despite the range of treatment options available for diabetes patients, not all patients benefit from them. Investigating how different pathways correlate with phenotype of interest may help unravel novel drug targets and discover a possible cure. Many pathway-based methods have been developed to incorporate biological knowledge into the study of microarray data. Most of these methods can only analyze individual pathways but cannot deal with two or more pathways in a model based framework. This represents a serious limitation because, like genes, individual pathways do not work in isolation, and joint modeling may enable researchers to uncover patterns not seen in individual pathway-based analysis. In this paper, we propose a random effects model to analyze two or more pathways. We also derive score test statistics for significance of pathway effects. We apply our method to a microarray study of Type II diabetes. Our method may eludicate how pathways crosstalk with each other and facilitate the investigation of pathway crosstalks. Further hypothesis on the biological mechanisms underlying the disease and traits of interest may be generated and tested based on this method.
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina 27705, U.S.A. Tel.: +919-681-5011.
authors.forename: Herbert
authors.initials: H
authors.lastname: Pang
authors.affiliation: Department of Statistics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, U.S.A. Tel.: +540-231-5366.
authors.forename: Inyoung
authors.initials: I
authors.lastname: Kim
authors.affiliation: Department of Biostatistics, Yale School of Public Health, and Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, U.S.A. Tel.: +203-785-6271.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
keywords: Diabetes; Gene expression analysis; Microarray; Pathway tests; Random pathway effects; Score test