Topology prediction for helical transmembrane proteins at 86% accuracy
Topology prediction for helical transmembrane proteins at 86% accuracy
复制标题
DOI：
10.1002/pro.5560050824
复制
发表时间：
1996-08-01
期刊：
影响因子：
8
通讯作者：
Casadio, R
中科院分区：
文献类型：
--
作者：
Rost, B;Fariselli, P;Casadio, R
以前，我们介绍了一种基于进化谱预测跨膜螺旋（HTM）位置的神经网络系统（PHDhtm，Rest B，Casadio R，Fariselli P，Sander C，1995，Protein Sci 4：521-533）。在这里，我们描述了该系统的改进和扩展。这种改进是通过一种类似动态规划的算法来实现的，该算法优化了与神经网络输出兼容的螺旋。扩展是通过将带正电荷的残基在细胞质外区域中更丰富的观察应用于精细预测来预测拓扑结构（第一环区域相对于膜的取向）。此外，我们引入了一种方法来减少误报的数量，即，蛋白质错误地预测与膜螺旋。预测准确性的评估是基于交叉验证和双盲测试集（总共131种蛋白质）。最终的方法似乎比其他公布的方法更准确：（1）对于几乎89%（+/-3%）的测试蛋白质，所有HTM都被正确预测。(2)对于超过86%（+/-3%）的蛋白质，拓扑结构被正确预测。(3)我们定义的可靠性指标与预测精度相关：对于一半的蛋白质，段的准确性提高到98%;和三分之二，拓扑预测的准确性是95%。(4)错误预测HTM的蛋白质比率低于2%（+/-1%）。最后，将该方法应用于1，616个流感嗜血杆菌序列。我们预测19%的基因组序列包含一个或多个HTM。这似乎低于我们先前对酵母VIII染色体的预测（约25%）。
Previously, we introduced a neural network system predicting locations of transmembrane helices (HTMs) based on evolutionary profiles (PHDhtm, Rest B, Casadio R, Fariselli P, Sander C, 1995, Protein Sci 4:521-533). Here, we describe an improvement and an extension of that system. The improvement is achieved by a dynamic programming-like algorithm that optimizes helices compatible with the neural network output. The extension is the prediction of topology (orientation of first loop region with respect to membrane) by applying to the refined prediction the observation that positively charged residues are more abundant in extra-cytoplasmic regions. Furthermore, we introduce a method to reduce the number of false positives, i.e., proteins falsely predicted with membrane helices. The evaluation of prediction accuracy is based on a cross-validation and a double-blind test set (in total 131 proteins). The final method appears to be more accurate than other methods published: (1) For almost 89% (+/-3%) of the test proteins, all HTMs are predicted correctly. (2) For more than 86% (+/-3%) of the proteins, topology is predicted correctly. (3) We define reliability indices that correlate with prediction accuracy: for one half of the proteins, segment accuracy raises to 98%; and for two-thirds, accuracy of topology prediction is 95%. (4) The rate of proteins for which HTMs are predicted falsely is below 2% (+/-1%). Finally, the method is applied to 1,616 sequences of Haemophilus influenzae. We predict 19% of the genome sequences to contain one or more HTMs. This appears to be lower than what we predicted previously for the yeast VIII chromosome (about 25%).