accurate prediction of secreted substrates and identification of a conserved putative secretion signal for type iii secretion systems准确预测分泌基质和守恒的假定的分泌信号的识别iii型分泌系统.pdfVIP

Accurate Prediction of Secreted Substrates and Identification of a Conserved Putative Secretion Signal for Type III Secretion Systems 1 2 3 Ram Samudrala , Fred Heffron , Jason E. McDermott * 1 Department of Microbiology, University of Washington, Seattle, Washington, United States of America, 2 Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon, United States of America, 3 Computational Biology and Bioinformatics, Pacific Northwest National Laboratory, Richland, Washington, United States of America Abstract The type III secretion system is an essential component for virulence in many Gram-negative bacteria. Though components of the secretion system apparatus are conserved, its substrates—effector proteins—are not. We have used a novel computational approach to confidently identify new secreted effectors by integrating protein sequence-based features, including evolutionary measures such as the pattern of homologs in a range of other organisms, G+C content, amino acid composition, and the N-terminal 30 residues of the protein sequence. The method was trained on known effectors from the plant pathogen Pseudomonas syringae and validated on a set of effectors from the animal pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) after eliminating effectors with detectable sequence similarity. We show that this approach can predict known secreted effectors with high specificity and sensitivity. Furthermore, by considering a large set of effectors from multiple organisms, we computationally identify a common putative secretion signal in the N-terminal 20 residues of secreted effectors. This signal can be used to discriminate 46 out of 68 total known effectors from