Truncation of protein sequences for fast profile alignment with application to subcellular localization

M. Mak, Wei Wang, S. Kung
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Abstract

We have recently found that the computation time of homology-based subcellular localization can be substantially reduced by aligning profiles up to the cleavage site positions of signal peptides, mitochondrial targeting peptides, and chloro-plast transit peptides [1]. While the method can reduce the profile alignment time by as much as 20 folds, it cannot reduce the computation time spent on creating the profiles. In this paper, we propose a new approach that can reduce both the profile creation time and profile alignment time. In the new approach, instead of cutting the profiles, we shorten the sequences by cutting them at the cleavage site locations. The shortened sequences are then presented to PSI-BLAST to compute the profiles. Experimental results and analysis of profile-alignment score matrices suggest that both profile creation time and profile alignment time can be reduced without sacrificing subcellular localization accuracy. Once a pairwise profile-alignment score matrix has been obtained, a one-vs-rest SVM classifier can be trained. To further reduce the training and recognition time of the classifier, we propose a perturbation discriminant analysis (PDA) technique. It was found that PDA enjoys a short training time as compared to the conventional SVM.
截断蛋白质序列用于快速定位与亚细胞定位的应用
我们最近发现,通过对准信号肽、线粒体靶向肽和叶绿体转运肽的切割位点位置,可以大大减少基于同源的亚细胞定位的计算时间[1]。虽然该方法可以将轮廓线对齐时间减少20倍,但它不能减少创建轮廓线所花费的计算时间。在本文中,我们提出了一种既可以减少轮廓创建时间又可以减少轮廓对齐时间的新方法。在新的方法中,我们通过在解理位点处切割来缩短序列,而不是切割剖面。然后将缩短的序列提交给PSI-BLAST来计算剖面。实验结果和对轮廓线对齐得分矩阵的分析表明,在不牺牲亚细胞定位精度的情况下,可以减少轮廓线创建时间和轮廓线对齐时间。一旦获得了成对的轮廓对齐评分矩阵,就可以训练出一个一对一的支持向量机分类器。为了进一步减少分类器的训练和识别时间,我们提出了一种微扰判别分析(PDA)技术。结果表明,与传统支持向量机相比,PDA的训练时间较短。
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