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Submitted on December 26, 2001
Revised on March 20, 2002
Accepted on April 4, 2002

Protein interactions: Two methods for assessment of the reliability of high-throughput observations

Charlotte M. Deane, Lukasz Salwinski, Ioannis Xenarios, and David Eisenberg

DOE-MBI LSBMM, UCLA, Los Angeles, CA 90095-1507

Corresponding Author: david{at}mbi.ucla.edu

High-throughput methods for detecting protein interactions require assessment of their accuracy. We present two forms of computational assessment. The first method is the Expression Profile Reliability Index (EPR Index). The EPR index estimates the biologically relevant fraction of protein interactions detected in a high-throughput screen. It does so by comparing the RNA expression profiles for the proteins whose interactions are found in the screen with expression profiles for known interacting and non-interacting pairs of proteins. The second form of assessment is the Paralogous Verification Method (PVM). This method judges an interaction likely if the putatively interacting pair has paralogs that also interact. In contrast to the EPR index which evaluates datasets of interactions, PVM scores individual interactions. On a test set, PVM correctly identifies 40% of true interactions with a false positive rate of ~1%. EPR and PVM were applied to the Database of Interacting Proteins (DIP), a large and diverse collection of protein-protein interactions that contains over 8000 S. cerevisiae pairwise protein interactions. Using these two methods, we estimate that ~50% of them are reliable and with the aid of PVM we confidently identify 3003 of them. Web servers for both the PVM and EPR methods are available on the DIP website (http://dip.doe-mbi.ucla.edu/Services.cgi).


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