Title
Functional annotation of regulatory pathways.
Abstract
Standardized annotations of biomolecules in interaction networks (e.g. Gene Ontology) provide comprehensive understanding of the function of individual molecules. Extending such annotations to pathways is a critical component of functional characterization of cellular signaling at the systems level.We propose a framework for projecting gene regulatory networks onto the space of functional attributes using multigraph models, with the objective of deriving statistically significant pathway annotations. We first demonstrate that annotations of pairwise interactions do not generalize to indirect relationships between processes. Motivated by this result, we formalize the problem of identifying statistically overrepresented pathways of functional attributes. We establish the hardness of this problem by demonstrating the non-monotonicity of common statistical significance measures. We propose a statistical model that emphasizes the modularity of a pathway, evaluating its significance based on the coupling of its building blocks. We complement the statistical model by an efficient algorithm and software, Narada, for computing significant pathways in large regulatory networks. Comprehensive results from our methods applied to the Escherichia coli transcription network demonstrate that our approach is effective in identifying known, as well as novel biological pathway annotations.Narada is implemented in Java and is available at http://www.cs.purdue.edu/homes/jpandey/narada/.
Year
DOI
Venue
2007
10.1093/bioinformatics/btm203
ISMB/ECCB (Supplement of Bioinformatics)
Keywords
Field
DocType
common statistical significance measure,novel biological pathway annotation,comprehensive understanding,functional annotation,significant pathway,functional attribute,functional characterization,comprehensive result,significant pathway annotation,regulatory pathway,overrepresented pathway,statistical model,gene regulatory network,escherichia coli,interaction network,statistical significance
Data mining,Computer science,Software,Artificial intelligence,Pairwise comparison,Annotation,Multigraph,Statistical model,Bioinformatics,Gene regulatory network,Java,Machine learning,Modularity
Conference
Volume
Issue
ISSN
23
13
1367-4811
Citations 
PageRank 
References 
9
0.61
11
Authors
6
Name
Order
Citations
PageRank
Jayesh Pandey1392.20
Mehmet Koyutürk269353.38
Yohan Kim390.95
Wojciech Szpankowski41557192.33
Shankar Subramaniam538546.50
Ananth Grama61812136.25