Precision and recall estimates for two-hybrid screens.
Precision and recall estimates for two-hybrid screens.
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DOI：
10.1093/bioinformatics/btn640
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发表时间：
2009-02-01
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影响因子：
--
通讯作者：
Bader JS
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文献类型：
--
作者：
Huang H;Bader JS
动机：酵母双杂交筛选是绘制两两蛋白相互作用图谱的重要方法。这种方法可能产生虚假的相互作用（错误的发现），并且可能错过真实的相互作用（假阴性）。以前，我们报道了一个捕获-再捕获估计器，用于特定诱饵的精度和召回率。在这里，我们提出了一种改进的方法，可以更好地解释诱饵特定错误率的异质性。结果：酵母、蠕虫和蝇类筛查的总体错误发现率（FDRs）分别为9.9%、13.2%和17.0%，假阴性率（fnr）分别为51%、42%和28%。然后使用诱饵特异性fdr和估计的蛋白质度来确定产生更多（或更少）假阳性相互作用和更多（或更少）相互作用伙伴的蛋白质类别。虽然膜蛋白被认为会提高fdr，但目前的分析表明，内在膜蛋白实际上可能会降低fdr。疏水性与降低错误率和减少相互作用伙伴正相关。这些方法将有助于未来的双杂交筛选，可以使用超高通量测序对相互作用的诱饵-猎物对进行更深入的采样。可用性：所有软件（C源代码）和数据集都可以作为补充文件在http://www.baderzone.org上获得，根据Lesser GPL v. 3许可。补充信息：补充数据可在Bioinformatics在线获取。
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@jhu.edu Supplementary information: Supplementary data are available at Bioinformatics online.
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