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Originally published In Press as doi:10.1074/mcp.M100037-MCP200 on April 4, 2002.
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Molecular & Cellular Proteomics 1:349-356, 2002.
© 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

Research

Protein Interactions

Two Methods for Assessment of the Reliability of High Throughput Observations*

Charlotte M. Deane{ddagger},§, Lukasz Salwinski{ddagger}, Ioannis Xenarios and David Eisenberg

From the Howard Hughes Medical Institute, Molecular Biology Institute, UCLA-Department of Energy Laboratory of Structural Biology and Molecular Medicine, University of California, Los Angeles, California 90095-1570

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 (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 identifies correctly 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 Saccharomyces cerevisiae pairwise protein interactions. Using these two methods, we estimate that ~50% of them are reliable, and with the aid of PVM we identify confidently 3003 of them. Web servers for both the PVM and EPR methods are available on the DIP website (dip.doe-mbi.ucla.edu/Services.cgi).

To whom correspondence should be addressed: Howard Hughes Medical Inst., Molecular Biology Inst., UCLA-DOE Laboratory of Structural Biology and Molecular Medicine, University of California, Los Angeles, P.O. Box 951570, Los Angeles, CA 90095-1570. Tel.: 310-825-3754; Fax: 310-206-3914; E-mail: david{at}mbi.ucla.edu.


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