Reference: Huang H and Bader JS (2009) Precision and recall estimates for two-hybrid screens. Bioinformatics 25(3):372-8

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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@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.

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Journal Article
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Huang H, Bader JS
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