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The Scientific World Journal
Volume 2013, Article ID 948617, 10 pages
Research Article

Feature-Based Classification of Amino Acid Substitutions outside Conserved Functional Protein Domains

Centre for Multidisciplinary Research and Engineering, Vinca Institute of Nuclear Sciences, University of Belgrade, 12-14 Mihajla Petrovica Alasa, 11001 Belgrade, Serbia

Received 30 August 2013; Accepted 24 September 2013

Academic Editors: J. Golebiowski and J. Yu

Copyright © 2013 Branislava Gemovic et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


There are more than 500 amino acid substitutions in each human genome, and bioinformatics tools irreplaceably contribute to determination of their functional effects. We have developed feature-based algorithm for the detection of mutations outside conserved functional domains (CFDs) and compared its classification efficacy with the most commonly used phylogeny-based tools, PolyPhen-2 and SIFT. The new algorithm is based on the informational spectrum method (ISM), a feature-based technique, and statistical analysis. Our dataset contained neutral polymorphisms and mutations associated with myeloid malignancies from epigenetic regulators ASXL1, DNMT3A, EZH2, and TET2. PolyPhen-2 and SIFT had significantly lower accuracies in predicting the effects of amino acid substitutions outside CFDs than expected, with especially low sensitivity. On the other hand, only ISM algorithm showed statistically significant classification of these sequences. It outperformed PolyPhen-2 and SIFT by 15% and 13%, respectively. These results suggest that feature-based methods, like ISM, are more suitable for the classification of amino acid substitutions outside CFDs than phylogeny-based tools.