MemBrain: improving the accuracy of predicting transmembrane helices.

MemBrain: improving the accuracy of predicting transmembrane helices.
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DOI:
10.1371/journal.pone.0002399
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发表时间:
2008-06-11
期刊:
影响因子:
3.7
通讯作者:
Chou JJ
Chou JJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Shen H;Chou JJ

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预测α螺旋膜蛋白的跨膜螺旋(TMH)在高分辨率结构不可用的情况下提供了有关蛋白质拓扑结构的有价值的信息。许多预测已经开发基于氨基酸疏水性尺度或纯统计方法。虽然这些预测器在识别蛋白质中tmh的数量方面表现相当好,但它们通常在预测tmh的末端或异常长度的tmh时不准确。为了提高TMH检测的准确性,我们开发了一个基于机器学习的预测器MemBrain,它集成了多种现代生物信息学方法,包括多序列比对矩阵的序列表示、优化的证据理论k -最近邻预测算法、多预测窗口大小融合和动态阈值分类。MemBrain在预测精度上总体提高了约20%,特别是在预测TMHs末端和短于15个残基的TMHs末端方面。它还具有检测n端信号肽的能力。MemBrain预测器是一个有用的基于序列的分析工具,用于螺旋膜蛋白的功能和结构表征;它可以在http://chou.med.harvard.edu/bioinf/MemBrain/上免费获得。
Prediction of transmembrane helices (TMH) in α helical membrane proteins provides valuable information about the protein topology when the high resolution structures are not available. Many predictors have been developed based on either amino acid hydrophobicity scale or pure statistical approaches. While these predictors perform reasonably well in identifying the number of TMHs in a protein, they are generally inaccurate in predicting the ends of TMHs, or TMHs of unusual length. To improve the accuracy of TMH detection, we developed a machine-learning based predictor, MemBrain, which integrates a number of modern bioinformatics approaches including sequence representation by multiple sequence alignment matrix, the optimized evidence-theoretic K-nearest neighbor prediction algorithm, fusion of multiple prediction window sizes, and classification by dynamic threshold. MemBrain demonstrates an overall improvement of about 20% in prediction accuracy, particularly, in predicting the ends of TMHs and TMHs that are shorter than 15 residues. It also has the capability to detect N-terminal signal peptides. The MemBrain predictor is a useful sequence-based analysis tool for functional and structural characterization of helical membrane proteins; it is freely available at http://chou.med.harvard.edu/bioinf/MemBrain/.
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