Module-based association analysis for omics data with network structure.

TitleModule-based association analysis for omics data with network structure.
Publication TypeJournal Article
Year of Publication2015
AuthorsWang, Zhi, Arnab Maity, Chuhsing Kate Hsiao, Deepak Voora, Rima Kaddurah-Daouk, and Jung-Ying Tzeng
JournalPLoS One
Volume10
Issue3
Paginatione0122309
Date Published2015
ISSN1932-6203
KeywordsAlgorithms, Computational Biology, Computer Simulation, Gene Regulatory Networks, Humans, Polymorphism, Single Nucleotide
Abstract

Module-based analysis (MBA) aims to evaluate the effect of a group of biological elements sharing common features, such as SNPs in the same gene or metabolites in the same pathways, and has become an attractive alternative to traditional single bio-element approaches. Because bio-elements regulate and interact with each other as part of network, incorporating network structure information can more precisely model the biological effects, enhance the ability to detect true associations, and facilitate our understanding of the underlying biological mechanisms. However, most MBA methods ignore the network structure information, which depicts the interaction and regulation relationship among basic functional units in biology system. We construct the connectivity kernel and the topology kernel to capture the relationship among bio-elements in a module, and use a kernel machine framework to evaluate the joint effect of bio-elements. Our proposed kernel machine approach directly incorporates network structure so to enhance the study efficiency; it can assess interactions among modules, account covariates, and is computational efficient. Through simulation studies and real data application, we demonstrate that the proposed network-based methods can have markedly better power than the approaches ignoring network information under a range of scenarios.

DOI10.1371/journal.pone.0122309
Alternate JournalPLoS One
Original PublicationModule-based association analysis for omics data with network structure.
PubMed ID25822417
PubMed Central IDPMC4378989
Grant ListP01 CA142538 / CA / NCI NIH HHS / United States
R00 ES017744 / ES / NIEHS NIH HHS / United States
R01 MH084022 / MH / NIMH NIH HHS / United States
RC1 GM091083 / GM / NIGMS NIH HHS / United States
Project: