WS-SNPs&GO: a web server for predicting the deleterious effect of human protein variants using functional annotation

• Published in: BMC genomics Vol. 14; no. Suppl 3; p. S6
• Main Authors: Capriotti, Emidio, Calabrese, Remo, Fariselli, Piero, Martelli, Pier Luigi, Altman, Russ B, Casadio, Rita
• Format: Journal Article
• Language: English
• Published: London BioMed Central 2013
• Subjects: Algorithms; Amino Acid Substitution - genetics; Amino acids; Animal Genetics and Genomics; Biomedical and Life Sciences; Colleges & universities; Computational Biology - methods; Correlation coefficient; Disease; Experiments; Gene expression; Genetic Variation; Genomes; Humans; Internet; Life Sciences; Methods; Microarrays; Microbial Genetics and Genomics; Molecular Sequence Annotation - methods; Mutation; Plant Genetics and Genomics; Proteins; Proteins - chemistry; Proteins - genetics; Proteomics; Software; Sequence Profile; Reliability Index; Support Vector Machine; Protein Data Bank; Gene Ontology
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/1471-2164-14-S3-S6

Background SNPs&GO is a method for the prediction of deleterious Single Amino acid Polymorphisms (SAPs) using protein functional annotation. In this work, we present the web server implementation of SNPs&GO (WS-SNPs&GO). The server is based on Support Vector Machines (SVM) and for a given protein, its input comprises: the sequence and/or its three-dimensional structure (when available), a set of target variations and its functional Gene Ontology (GO) terms. The output of the server provides, for each protein variation, the probabilities to be associated to human diseases. Results The server consists of two main components, including updated versions of the sequence-based SNPs&GO (recently scored as one of the best algorithms for predicting deleterious SAPs) and of the structure-based SNPs&GO 3d programs. Sequence and structure based algorithms are extensively tested on a large set of annotated variations extracted from the SwissVar database. Selecting a balanced dataset with more than 38,000 SAPs, the sequence-based approach achieves 81% overall accuracy, 0.61 correlation coefficient and an Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve of 0.88. For the subset of ~6,600 variations mapped on protein structures available at the Protein Data Bank (PDB), the structure-based method scores with 84% overall accuracy, 0.68 correlation coefficient, and 0.91 AUC. When tested on a new blind set of variations, the results of the server are 79% and 83% overall accuracy for the sequence-based and structure-based inputs, respectively. Conclusions WS-SNPs&GO is a valuable tool that includes in a unique framework information derived from protein sequence, structure, evolutionary profile, and protein function. WS-SNPs&GO is freely available at http://snps.biofold.org/snps-and-go .