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Predicting deleterious non-synonymous single nucleotide polymorphisms in signal peptides based on hybrid sequence attributes. (English) Zbl 1244.92019
Summary: Signal peptides play a crucial role in various biological processes, such as localization of cell surface receptors, translocation of secreted proteins and cell-cell communication. However, the amino acid mutation in signal peptides, also called non-synonymous single nucleotide polymorphisms (nsSNPs or SAPs), may lead to the loss of their functions. In the present study, a computational method was proposed for predicting deleterious nsSNPs in signal peptides based on random forests (RFs) by incorporating position specific scoring matrix (PSSM) profiles, SignalP score and physicochemical properties. These features were optimized by the maximum relevance minimum redundancy (mRMR) method. Then, a cost matrix was used to minimize the effect of the imbalanced data classification problem that usually occurred in nsSNPs prediction. The method achieved an overall accuracy of 84.5% and the area under the ROC curve (AUC) of 0.822 by a jackknife test, when the optimal subset included 10 features. Furthermore, on the same data set, we compared our predictor with other existing methods, including the R-score-based method and D-score-based methods, and the result of our method was superior to those of the two methods. The satisfactory performance suggests that our method is effective in predicting the deleterious nsSNPs in signal peptides.

92C40 Biochemistry, molecular biology
92C37 Cell biology
62P10 Applications of statistics to biology and medical sciences; meta analysis
92-08 Computational methods for problems pertaining to biology
jackknife test
Full Text: DOI
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