Discovering reliable protein interactions from high-throughput experimental data using network topology.
OBJECTIVE
Current protein-protein interaction (PPI) detection via high-throughput experimental methods, such as yeast-two-hybrid has been reported to be highly erroneous, leading to potentially costly spurious discoveries. This work introduces a novel measure called IRAP, i.e. "interaction reliability by alternative path", for assessing the reliability of protein interactions based on the underlying topology of the PPI network.


METHODS
A candidate PPI is considered to be reliable if it is involved in a closed loop in which the alternative path of interactions between the two interacting proteins is strong. We devise an algorithm called AlternativePathFinder to compute the IRAP value for each interaction in a complex PPI network. Validation of the IRAP as a measure for assessing the reliability of PPIs is performed with extensive experiments on yeast PPI data. All the data used in our experiments can be downloaded from our supplementary data web site at .


RESULTS
Results show consistently that IRAP measure is an effective way for discovering reliable PPIs in large datasets of error-prone experimentally-derived PPIs. Results also indicate that IRAP is better than IG2, and markedly better than the more simplistic IG1 measure.


CONCLUSIONS
Experimental results demonstrate that a global, system-wide approach-such as IRAP that considers the entire interaction network instead of merely local neighbors-is a much more promising approach for assessing the reliability of PPIs.
Chen
Jin
J
School of Computing, National University of Singapore, Singapore 119260, Singapore. chenjin@comp.nus.edu.sg
Hsu
Wynne
W
Lee
Mong Li
ML
Ng
See-Kiong
SK
D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics; D015870:Gene Expression; D008954:Models, Biological; D025941:Protein Interaction Mapping / Q000379:methods*; D015203:Reproducibility of Results; D015003:Yeasts / Q000737:chemistry / Q000235:genetics
D005656:Fungal Proteins