Feature-Based Classification of Amino Acid Substitutions outside Conserved Functional Protein Domains
Апстракт
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.
Извор:
Scientific World Journal, 2013Финансирање / пројекти:
- Примена EIIP/ISM биоинформатичке платформе у откривању нових терапеутских таргета и потенцијалних терапеутских молекула (RS-MESTD-Basic Research (BR or ON)-173001)
DOI: 10.1155/2013/948617
ISSN: 1537-744X
WoS: 000327645300001
Scopus: 2-s2.0-84890056814
Колекције
Институција/група
VinčaTY - JOUR AU - Gemović, Branislava S. AU - Perović, Vladimir R. AU - Glišić, Sanja AU - Veljković, Nevena V. PY - 2013 UR - https://vinar.vin.bg.ac.rs/handle/123456789/5770 AB - 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. T2 - Scientific World Journal T1 - Feature-Based Classification of Amino Acid Substitutions outside Conserved Functional Protein Domains DO - 10.1155/2013/948617 ER -
@article{ author = "Gemović, Branislava S. and Perović, Vladimir R. and Glišić, Sanja and Veljković, Nevena V.", year = "2013", abstract = "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.", journal = "Scientific World Journal", title = "Feature-Based Classification of Amino Acid Substitutions outside Conserved Functional Protein Domains", doi = "10.1155/2013/948617" }
Gemović, B. S., Perović, V. R., Glišić, S.,& Veljković, N. V.. (2013). Feature-Based Classification of Amino Acid Substitutions outside Conserved Functional Protein Domains. in Scientific World Journal. https://doi.org/10.1155/2013/948617
Gemović BS, Perović VR, Glišić S, Veljković NV. Feature-Based Classification of Amino Acid Substitutions outside Conserved Functional Protein Domains. in Scientific World Journal. 2013;. doi:10.1155/2013/948617 .
Gemović, Branislava S., Perović, Vladimir R., Glišić, Sanja, Veljković, Nevena V., "Feature-Based Classification of Amino Acid Substitutions outside Conserved Functional Protein Domains" in Scientific World Journal (2013), https://doi.org/10.1155/2013/948617 . .