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Bioinformatics Advance Access published online on December 17, 2008
Bioinformatics, doi:10.1093/bioinformatics/btn640
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© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Precision and recall estimates for two-hybrid screens

Hailiang Huang and Joel S. Bader *

Department of Biomedical Engineering and High-Throughput Biology Center, Johns Hopkins University, Baltimore, Mary-land, United States of America.

*To whom correspondence should be addressed. Dr. Joel S. Bader, E-mail: joel.bader{at}jhu.edu


  Abstract

Motivation: Yeast two-hybrid screens are an important method to map pairwise protein interactions. This method can generate spurious interactions (false discoveries), and true interactions can be missed (false negatives). Previously we reported a capture-recapture estimator for bait-specific precision and recall. Here we present an improved method that better accounts for heterogeneity in bait-specific error rates.

Results: For yeast, worm, and fly screens, we estimate the overall false-discovery rates to be 9.9%, 13.2% and 17.0% and the false-negative rates to be 51%, 42% and 28%. Bait-specific false-discovery rates and the estimated protein degrees are then used to identify protein categories that yield more (or fewer) false-positive interactions and more (or fewer) interaction partners. While membrane proteins have been suggested to have elevated false-discovery rates, the current analysis suggests that intrinsic membrane proteins may actually have reduced false-discovery rates. Hydrophobicity is positively correlated with decreased error rates and fewer interaction partners. These methods will be useful for future two-hybrid screens, which could use ultra-high-throughput sequencing for deeper sampling of interacting bait-prey pairs.

Contact: joel.bader{at}jhu.edu

Supplementary information: All software (C source) and datasets are available as supplemental files and at http://www.baderzone.org under the Lesser GPL v. 3 license.

Associate Editor: Prof. Alfonso Valencia

Received on July 10, 2008; revised on November 23, 2008; accepted on December 10, 2008

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