Module Discovery by Exhaustive Search for Densely Connected, Co-Expressed Regions in Biomolecular Interaction Networks

Peer reviewed: 
Yes, item is peer reviewed.
Scholarly level: 
Faculty/Staff
Final version published as: 

Colak R, Moser F, Chu JS-C, Schönhuth A, Chen N, et al. (2010) Module Discovery by Exhaustive Search for Densely Connected, Co-Expressed Regions in Biomolecular Interaction Networks. PLoS ONE 5(10): e13348. doi:10.1371/journal.pone.0013348

Date created: 
2010
Abstract: 

Background

Computational prediction of functionally related groups of genes (functional modules) from large-scale data is an important issue in computational biology. Gene expression experiments and interaction networks are well studied large-scale data sources, available for many not yet exhaustively annotated organisms. It has been well established, when analyzing these two data sources jointly, modules are often reflected by highly interconnected (dense) regions in the interaction networks whose participating genes are co-expressed. However, the tractability of the problem had remained unclear and methods by which to exhaustively search for such constellations had not been presented.

Methodology/Principal Findings

We provide an algorithmic framework, referred to as Densely Connected Biclustering (DECOB), by which the aforementioned search problem becomes tractable. To benchmark the predictive power inherent to the approach, we computed all co-expressed, dense regions in physical protein and genetic interaction networks from human and yeast. An automatized filtering procedure reduces our output which results in smaller collections of modules, comparable to state-of-the-art approaches. Our results performed favorably in a fair benchmarking competition which adheres to standard criteria. We demonstrate the usefulness of an exhaustive module search, by using the unreduced output to more quickly perform GO term related function prediction tasks. We point out the advantages of our exhaustive output by predicting functional relationships using two examples.

Conclusion/Significance

We demonstrate that the computation of all densely connected and co-expressed regions in interaction networks is an approach to module discovery of considerable value. Beyond confirming the well settled hypothesis that such co-expressed, densely connected interaction network regions reflect functional modules, we open up novel computational ways to comprehensively analyze the modular organization of an organism based on prevalent and largely available large-scale datasets.

Language: 
English
Document type: 
Article
File(s): 
Sponsor(s): 
Canadian Institute for Health Research
Michael Smith Foundation for Health Research (MSFHR)
Simon Fraser University Community Trust Endowment Fund
Pacific Institute for the Mathematical Sciences (PIMS)
National Sciences and Engineering Research Council (NSERC)
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