Journal
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
Volume 57, Issue 4, Pages 811-819Publisher
WILEY
DOI: 10.1002/prot.20252
Keywords
SNPs; disease-associated mutations; protein sequence; bioinformatics; neural networks; sequence variability
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Funding
- ICREA Funding Source: Custom
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The development of methods to assess the impact of amino acid mutations on human health has become an important goal in biomedical research, due to the growing number of nonsynonymous SNPs identified. Within this context, computational methods constitute a valuable tool, because they can easily process large amounts of mutations and give useful, almost cost-free, information on their pathological character. In this paper we present a computational approach to the prediction of disease-associated amino acid mutations, using only sequence-based information (amino acid properties, evolutionary information, secondary structure and accessibility predictions, and database annotations) and neural networks, as a model building tool. Mutations are predicted to be either pathological or neutral. Our results show that the method has a good overall success rate, 83%, that can reach 95% when trained for specific proteins. The methodology is fast and flexible enough to provide good estimates of the pathological character of large sets of nonsynonymous SNPs, but can also be easily adapted to give more precise predictions for proteins of special biomedical interest. (C) 2004 Wiley-Liss, Inc.
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