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Bioinformatics Advance Access originally published online on December 17, 2008
Bioinformatics 2009 25(3):372-378; 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, MD, USA

*To whom correspondence should be addressed.


  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.

Result: For yeast, worm and fly screens, we estimate the overall false discovery rates (FDRs) to be 9.9%, 13.2% and 17.0% and the false negative rates (FNRs) to be 51%, 42% and 28%. Bait-specific FDRs 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 FDRs, the current analysis suggests that intrinsic membrane proteins may actually have reduced FDRs. 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.

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

Contact: joel.bader{at}jhu.edu

Supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: Alfonso Valencia

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

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