Title
An integrative approach to inferring biologically meaningful gene modules.
Abstract
The ability to construct biologically meaningful gene networks and modules is critical for contemporary systems biology. Though recent studies have demonstrated the power of using gene modules to shed light on the functioning of complex biological systems, most modules in these networks have shown little association with meaningful biological function. We have devised a method which directly incorporates gene ontology (GO) annotation in construction of gene modules in order to gain better functional association.We have devised a method, Semantic Similarity-Integrated approach for Modularization (SSIM) that integrates various gene-gene pairwise similarity values, including information obtained from gene expression, protein-protein interactions and GO annotations, in the construction of modules using affinity propagation clustering. We demonstrated the performance of the proposed method using data from two complex biological responses: 1. the osmotic shock response in Saccharomyces cerevisiae, and 2. the prion-induced pathogenic mouse model. In comparison with two previously reported algorithms, modules identified by SSIM showed significantly stronger association with biological functions.The incorporation of semantic similarity based on GO annotation with gene expression and protein-protein interaction data can greatly enhance the functional relevance of inferred gene modules. In addition, the SSIM approach can also reveal the hierarchical structure of gene modules to gain a broader functional view of the biological system. Hence, the proposed method can facilitate comprehensive and in-depth analysis of high throughput experimental data at the gene network level.
Year
DOI
Venue
2011
10.1186/1752-0509-5-117
BMC systems biology
Keywords
Field
DocType
gene expression,semantic similarity,systems biology,system biology,affinity propagation,gene regulatory networks,algorithms,osmotic pressure,gene network,biological systems,high throughput,bioinformatics,protein protein interaction
Semantic similarity,Protein Interaction Map,Annotation,Biology,Gene ontology,Systems biology,Gene Modules,Bioinformatics,Molecular Sequence Annotation,Gene regulatory network
Journal
Volume
Issue
ISSN
5
1
1752-0509
Citations 
PageRank 
References 
7
0.37
20
Authors
3
Name
Order
Citations
PageRank
Jihoon Cho172.40
Kai Wang270.71
David J. Galas319329.73