Alignment-free method for functional annotation of amino acid substitutions: Application on epigenetic factors involved in hematologic malignancies
Аутори
Gemović, Branislava S.Perović, Vladimir R.
Davidović, Radoslav S.
Drljača, Tamara
Veljković, Nevena V.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
For the last couple of decades, there has been a significant growth in sequencing data, leading to an extraordinary increase in the number of gene variants. This places a challenge on the bioinformatics research community to develop and improve computational tools for functional annotation of new variants. Genes coding for epigenetic regulators have important roles in cancer pathogenesis and mutations in these genes show great potential as clinical biomarkers, especially in hematologic malignancies. Therefore, we developed a model that specifically focuses on these genes, with an assumption that it would outperform general models in predicting the functional effects of amino acid substitutions. EpiMut is a standalone software that implements a sequence based alignment-free method. We applied a two-step approach for generating sequence based features, relying on the biophysical and biochemical indices of amino acids and the Fourier Transform as a sequence transformation method. For each... gene in the dataset, the machine learning algorithm–Naïve Bayes was used for building a model for prediction of the neutral or disease-related status of variants. EpiMut outperformed state-of-the-art tools used for comparison, PolyPhen-2, SIFT and SNAP2. Additionally, EpiMut showed the highest performance on the subset of variants positioned outside conserved functional domains of analysed proteins, which represents an important group of cancer-related variants. These results imply that EpiMut can be applied as a first choice tool in research of the impact of gene variants in epigenetic regulators, especially in the light of the biomarker role in hematologic malignancies. EpiMut is freely available at https://www.vin.bg.ac.rs/180/tools/epimut.php.
Извор:
PLOS One, 2021, 16, 1, e0244948-Финансирање / пројекти:
- Примена EIIP/ISM биоинформатичке платформе у откривању нових терапеутских таргета и потенцијалних терапеутских молекула (RS-MESTD-Basic Research (BR or ON)-173001)
Напомена:
- EpiMut is freely available at https://www.vin.bg.ac.rs/180/tools/epimut.php.
DOI: 10.1371/journal.pone.0244948
ISSN: 1932-6203
PubMed: 33395407
WoS: 000607069100008
Scopus: 2-s2.0-85099331915
Институција/група
VinčaTY - JOUR AU - Gemović, Branislava S. AU - Perović, Vladimir R. AU - Davidović, Radoslav S. AU - Drljača, Tamara AU - Veljković, Nevena V. PY - 2021 UR - https://vinar.vin.bg.ac.rs/handle/123456789/8894 AB - For the last couple of decades, there has been a significant growth in sequencing data, leading to an extraordinary increase in the number of gene variants. This places a challenge on the bioinformatics research community to develop and improve computational tools for functional annotation of new variants. Genes coding for epigenetic regulators have important roles in cancer pathogenesis and mutations in these genes show great potential as clinical biomarkers, especially in hematologic malignancies. Therefore, we developed a model that specifically focuses on these genes, with an assumption that it would outperform general models in predicting the functional effects of amino acid substitutions. EpiMut is a standalone software that implements a sequence based alignment-free method. We applied a two-step approach for generating sequence based features, relying on the biophysical and biochemical indices of amino acids and the Fourier Transform as a sequence transformation method. For each gene in the dataset, the machine learning algorithm–Naïve Bayes was used for building a model for prediction of the neutral or disease-related status of variants. EpiMut outperformed state-of-the-art tools used for comparison, PolyPhen-2, SIFT and SNAP2. Additionally, EpiMut showed the highest performance on the subset of variants positioned outside conserved functional domains of analysed proteins, which represents an important group of cancer-related variants. These results imply that EpiMut can be applied as a first choice tool in research of the impact of gene variants in epigenetic regulators, especially in the light of the biomarker role in hematologic malignancies. EpiMut is freely available at https://www.vin.bg.ac.rs/180/tools/epimut.php. T2 - PLOS One T1 - Alignment-free method for functional annotation of amino acid substitutions: Application on epigenetic factors involved in hematologic malignancies VL - 16 IS - 1 SP - e0244948 DO - 10.1371/journal.pone.0244948 ER -
@article{ author = "Gemović, Branislava S. and Perović, Vladimir R. and Davidović, Radoslav S. and Drljača, Tamara and Veljković, Nevena V.", year = "2021", abstract = "For the last couple of decades, there has been a significant growth in sequencing data, leading to an extraordinary increase in the number of gene variants. This places a challenge on the bioinformatics research community to develop and improve computational tools for functional annotation of new variants. Genes coding for epigenetic regulators have important roles in cancer pathogenesis and mutations in these genes show great potential as clinical biomarkers, especially in hematologic malignancies. Therefore, we developed a model that specifically focuses on these genes, with an assumption that it would outperform general models in predicting the functional effects of amino acid substitutions. EpiMut is a standalone software that implements a sequence based alignment-free method. We applied a two-step approach for generating sequence based features, relying on the biophysical and biochemical indices of amino acids and the Fourier Transform as a sequence transformation method. For each gene in the dataset, the machine learning algorithm–Naïve Bayes was used for building a model for prediction of the neutral or disease-related status of variants. EpiMut outperformed state-of-the-art tools used for comparison, PolyPhen-2, SIFT and SNAP2. Additionally, EpiMut showed the highest performance on the subset of variants positioned outside conserved functional domains of analysed proteins, which represents an important group of cancer-related variants. These results imply that EpiMut can be applied as a first choice tool in research of the impact of gene variants in epigenetic regulators, especially in the light of the biomarker role in hematologic malignancies. EpiMut is freely available at https://www.vin.bg.ac.rs/180/tools/epimut.php.", journal = "PLOS One", title = "Alignment-free method for functional annotation of amino acid substitutions: Application on epigenetic factors involved in hematologic malignancies", volume = "16", number = "1", pages = "e0244948", doi = "10.1371/journal.pone.0244948" }
Gemović, B. S., Perović, V. R., Davidović, R. S., Drljača, T.,& Veljković, N. V.. (2021). Alignment-free method for functional annotation of amino acid substitutions: Application on epigenetic factors involved in hematologic malignancies. in PLOS One, 16(1), e0244948. https://doi.org/10.1371/journal.pone.0244948
Gemović BS, Perović VR, Davidović RS, Drljača T, Veljković NV. Alignment-free method for functional annotation of amino acid substitutions: Application on epigenetic factors involved in hematologic malignancies. in PLOS One. 2021;16(1):e0244948. doi:10.1371/journal.pone.0244948 .
Gemović, Branislava S., Perović, Vladimir R., Davidović, Radoslav S., Drljača, Tamara, Veljković, Nevena V., "Alignment-free method for functional annotation of amino acid substitutions: Application on epigenetic factors involved in hematologic malignancies" in PLOS One, 16, no. 1 (2021):e0244948, https://doi.org/10.1371/journal.pone.0244948 . .