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贝叶斯推断在基因组数据整合中减少了预测蛋白质-蛋白质相互作用的错误分类率。

Bayesian inference for genomic data integration reduces misclassification rate in predicting protein-protein interactions.

机构信息

Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, United States of America.

出版信息

PLoS Comput Biol. 2011 Jul;7(7):e1002110. doi: 10.1371/journal.pcbi.1002110. Epub 2011 Jul 28.

Abstract

Protein-protein interactions (PPIs) are essential to most fundamental cellular processes. There has been increasing interest in reconstructing PPIs networks. However, several critical difficulties exist in obtaining reliable predictions. Noticeably, false positive rates can be as high as >80%. Error correction from each generating source can be both time-consuming and inefficient due to the difficulty of covering the errors from multiple levels of data processing procedures within a single test. We propose a novel Bayesian integration method, deemed nonparametric Bayes ensemble learning (NBEL), to lower the misclassification rate (both false positives and negatives) through automatically up-weighting data sources that are most informative, while down-weighting less informative and biased sources. Extensive studies indicate that NBEL is significantly more robust than the classic naïve Bayes to unreliable, error-prone and contaminated data. On a large human data set our NBEL approach predicts many more PPIs than naïve Bayes. This suggests that previous studies may have large numbers of not only false positives but also false negatives. The validation on two human PPIs datasets having high quality supports our observations. Our experiments demonstrate that it is feasible to predict high-throughput PPIs computationally with substantially reduced false positives and false negatives. The ability of predicting large numbers of PPIs both reliably and automatically may inspire people to use computational approaches to correct data errors in general, and may speed up PPIs prediction with high quality. Such a reliable prediction may provide a solid platform to other studies such as protein functions prediction and roles of PPIs in disease susceptibility.

摘要

蛋白质-蛋白质相互作用 (PPIs) 是大多数基本细胞过程所必需的。人们对重建蛋白质相互作用网络越来越感兴趣。然而,在获得可靠的预测方面存在几个关键的困难。值得注意的是,假阳性率可能高达>80%。由于在单个测试中难以涵盖来自多个数据处理层次的错误,因此从每个生成源进行错误纠正既耗时又效率低下。我们提出了一种新颖的贝叶斯集成方法,称为非参数贝叶斯集成学习 (NBEL),通过自动对信息量最大的数据源进行加权,同时对信息量较小和有偏差的数据源进行加权,从而降低错误分类率(包括假阳性和假阴性)。广泛的研究表明,NBEL 比经典的朴素贝叶斯对不可靠、易出错和受污染的数据更稳健。在一个大型人类数据集上,我们的 NBEL 方法预测了比朴素贝叶斯更多的蛋白质相互作用。这表明以前的研究可能不仅有大量的假阳性,而且还有假阴性。对具有高质量的两个人类蛋白质相互作用数据集的验证支持了我们的观察结果。我们的实验表明,通过大大减少假阳性和假阴性,计算上预测高通量蛋白质相互作用是可行的。可靠且自动预测大量蛋白质相互作用的能力可能会激发人们使用计算方法来纠正一般数据错误,并可能加速高质量蛋白质相互作用的预测。这样可靠的预测可能为其他研究提供一个坚实的平台,如蛋白质功能预测和蛋白质相互作用在疾病易感性中的作用。

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