PathNet: A tool for pathway analysis using topological information by Bhaskar Dutta, Anders Wallqvist and Jaques Reifman. (Source Code for Biology and Medicine 2012, 7:10 doi:10.1186/1751-0473-7-10)
Abstract:
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 highthroughput 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.
Results
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 Alzheimers disease microarray datasets, and compared its performance with existing methods. Importantly, PathNet identified deregulation of the ubiquitin-mediated proteolysis pathway as an important component in Alzheimers disease progression, despite the absence of this pathway in the standard enrichment analyses.
Conclusions
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/.
Important work for genomics but also a reminder that a list of paths is just that, a list of paths.
The value-add and creative aspect of data analysis is in the scoring of those paths in order to wring more information from them.
How is it for you? Just lists of paths or something a bit more clever?