Title
Network topology-based detection of differential gene regulation and regulatory switches in cell metabolism and signaling.
Abstract
Common approaches to pathway analysis treat pathways merely as lists of genes disregarding their topological structures, that is, ignoring the genes' interactions on which a pathway's cellular function depends. In contrast, PathWave has been developed for the analysis of high-throughput gene expression data that explicitly takes the topology of networks into account to identify both global dysregulation of and localized (switch-like) regulatory shifts within metabolic and signaling pathways. For this purpose, it applies adjusted wavelet transforms on optimized 2D grid representations of curated pathway maps.Here, we present the new version of PathWave with several substantial improvements including a new method for optimally mapping pathway networks unto compact 2D lattice grids, a more flexible and user-friendly interface, and pre-arranged 2D grid representations. These pathway representations are assembled for several species now comprising H. sapiens, M. musculus, D. melanogaster, D. rerio, C. elegans, and E. coli. We show that PathWave is more sensitive than common approaches and apply it to RNA-seq expression data, identifying crucial metabolic pathways in lung adenocarcinoma, as well as microarray expression data, identifying pathways involved in longevity of Drosophila.PathWave is a generic method for pathway analysis complementing established tools like GSEA, and the update comprises efficient new features. In contrast to the tested commonly applied approaches which do not take network topology into account, PathWave enables identifying pathways that are either known be involved in or very likely associated with such diverse conditions as human lung cancer or aging of D. melanogaster. The PathWave R package is freely available at http://www.ichip.de/software/pathwave.html.
Year
DOI
Venue
2014
10.1186/1752-0509-8-56
BMC systems biology
Keywords
Field
DocType
signal transduction,computational biology,gene regulatory networks,gene expression regulation,aging
Gene,Biology,Cell biology,Systems biology,Network topology,Regulation of gene expression,Signal transduction,Bioinformatics,Drosophila melanogaster,Gene regulatory network,Biological pathway
Journal
Volume
Issue
ISSN
8
1
1752-0509
Citations 
PageRank 
References 
2
0.34
5
Authors
8
Name
Order
Citations
PageRank
Rosario M. Piro1707.67
Stefan Wiesberg2244.14
Gunnar Schramm3643.08
Nico Rebel420.34
Marcus Oswald514716.01
Roland Eils664470.09
Gerhard Reinelt71481429.95
Rainer König81276.43