Title
PathNet: a tool for pathway analysis using topological information.
Abstract
<AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Identification of canonical pathways through enrichment of differentially expressed genes in a given pathway is a widely used method for interpreting gene lists generated from high-throughput experimental studies. However, most algorithms treat pathways as sets of genes, disregarding any inter- and intra-pathway connectivity information, and do not provide insights beyond identifying lists of pathways.We developed an algorithm (PathNet) that utilizes the connectivity information in canonical pathway descriptions to help identify study-relevant pathways and characterize non-obvious dependencies and connections among pathways using gene expression data. PathNet considers both the differential expression of genes and their pathway neighbors to strengthen the evidence that a pathway is implicated in the biological conditions characterizing the experiment. As an adjunct to this analysis, PathNet uses the connectivity of the differentially expressed genes among all pathways to score pathway contextual associations and statistically identify biological relations among pathways. In this study, we used PathNet to identify biologically relevant results in two Alzheimer's disease microarray datasets, and compared its performance with existing methods. Importantly, PathNet identified de-regulation of the ubiquitin-mediated proteolysis pathway as an important component in Alzheimer's disease progression, despite the absence of this pathway in the standard enrichment analyses.PathNet is a novel method for identifying enrichment and association between canonical pathways in the context of gene expression data. It takes into account topological information present in pathways to reveal biological information. PathNet is available as an R workspace image from http://www.bhsai.org/downloads/pathnet/.
Year
DOI
Venue
2012
10.1186/1751-0473-7-10
Source code for biology and medicine
Keywords
Field
DocType
alzheimer disease,gene expression,topology,genes,bioinformatics
Data mining,Differential expression,Gene,Microarray,Topological information,Contextual Associations,Computer science,Disease progression,Pathway analysis,Bioinformatics
Journal
Volume
Issue
ISSN
7
1
1751-0473
Citations 
PageRank 
References 
7
0.50
9
Authors
3
Name
Order
Citations
PageRank
Bhaskar Dutta121454.87
Anders Wallqvist220418.40
Jaques Reifman335632.72