Title
A network-based approach for predicting missing pathway interactions.
Abstract
Embedded within large-scale protein interaction networks are signaling pathways that encode response cascades in the cell. Unfortunately, even for well-studied species like S. cerevisiae, only a fraction of all true protein interactions are known, which makes it difficult to reason about the exact flow of signals and the corresponding causal relations in the network. To help address this problem, we introduce a framework for predicting new interactions that aid connectivity between upstream proteins (sources) and downstream transcription factors (targets) of a particular pathway. Our algorithms attempt to globally minimize the distance between sources and targets by finding a small set of shortcut edges to add to the network. Unlike existing algorithms for predicting general protein interactions, by focusing on proteins involved in specific responses our approach homes-in on pathway-consistent interactions. We applied our method to extend pathways in osmotic stress response in yeast and identified several missing interactions, some of which are supported by published reports. We also performed experiments that support a novel interaction not previously reported. Our framework is general and may be applicable to edge prediction problems in other domains.
Year
DOI
Venue
2012
10.1371/journal.pcbi.1002640
PLOS COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
osmotic pressure,signaling pathway,osmotic stress,algorithms,signal transduction,transcription factor
Osmotic stress response,ENCODE,Protein Interaction Networks,Protein–protein interaction,Pathway (interactions),Biology,Causal relations,Bioinformatics,Genetics,Small set,Transcription factor
Journal
Volume
Issue
ISSN
8
8
1553-734X
Citations 
PageRank 
References 
5
0.51
33
Authors
3
Name
Order
Citations
PageRank
Saket Navlakha139323.55
Anthony Gitter2476.07
Ziv Bar-Joseph31207112.00