Can We Use Standard Tools to Predict Functional Effects of Missense Gene Variations Outside Conserved Domains? TET2 Example
Апстракт
The most common genetic variations in humans are Single Nucleotide Polymorphisms (SNPs), so predicting their associations with cancers is a significant issue. Here, we were particularly interested in SNPs occurring outside protein Conserved Domains (CDs) of TET2, a recently discovered epigenetic regulator involved in leukemogenesis. Functional effects of TET2 gene variations were assessed with four publicly available tools: PhD-SNP, MutPred, PolyPhen-2 and SIFT. The methods were tested on the dataset of 166 SNPs and somatic TET2 mutations, and separately on the subset of 69 variations outside TET2 CDs. Abilities of tested tools to separate neutral SNPs from pathogenic mutations were similar to previously reported on complete TET2 dataset. However, we observed significantly lower accuracy of predictions outside CDs, ranging from 0.54 to 0.62. Also, areas under the ROC curves were low, 0.51-0.55. Correlations between predictions and positions of variations inside/outside CDs were signifi...cant and high, 0.46-0.78. Low efficiency of commonly used tools in predicting functional effects of variations outside CDs emphasize the need for new or modified algorithms.
Извор:
2nd International Conference “Theoretical Approaches to Bioinformation Systems” (TABIS.2013), September 17-22, 2013, Belgrade, Serbia, 2014, 65-71Финансирање / пројекти:
- Примена EIIP/ISM биоинформатичке платформе у откривању нових терапеутских таргета и потенцијалних терапеутских молекула (RS-MESTD-Basic Research (BR or ON)-173001)
Напомена:
- Proceedings available at: http://www.tabis2013.ipb.ac.rs/tabis2013.pdf
Институција/група
VinčaTY - CONF AU - Gemović, Branislava S. AU - Perović, Vladimir R. AU - Glišić, Sanja AU - Veljković, Nevena V. PY - 2014 UR - https://vinar.vin.bg.ac.rs/handle/123456789/10771 AB - The most common genetic variations in humans are Single Nucleotide Polymorphisms (SNPs), so predicting their associations with cancers is a significant issue. Here, we were particularly interested in SNPs occurring outside protein Conserved Domains (CDs) of TET2, a recently discovered epigenetic regulator involved in leukemogenesis. Functional effects of TET2 gene variations were assessed with four publicly available tools: PhD-SNP, MutPred, PolyPhen-2 and SIFT. The methods were tested on the dataset of 166 SNPs and somatic TET2 mutations, and separately on the subset of 69 variations outside TET2 CDs. Abilities of tested tools to separate neutral SNPs from pathogenic mutations were similar to previously reported on complete TET2 dataset. However, we observed significantly lower accuracy of predictions outside CDs, ranging from 0.54 to 0.62. Also, areas under the ROC curves were low, 0.51-0.55. Correlations between predictions and positions of variations inside/outside CDs were significant and high, 0.46-0.78. Low efficiency of commonly used tools in predicting functional effects of variations outside CDs emphasize the need for new or modified algorithms. C3 - 2nd International Conference “Theoretical Approaches to Bioinformation Systems” (TABIS.2013), September 17-22, 2013, Belgrade, Serbia T1 - Can We Use Standard Tools to Predict Functional Effects of Missense Gene Variations Outside Conserved Domains? TET2 Example SP - 65 EP - 71 UR - https://hdl.handle.net/21.15107/rcub_vinar_10771 ER -
@conference{ author = "Gemović, Branislava S. and Perović, Vladimir R. and Glišić, Sanja and Veljković, Nevena V.", year = "2014", abstract = "The most common genetic variations in humans are Single Nucleotide Polymorphisms (SNPs), so predicting their associations with cancers is a significant issue. Here, we were particularly interested in SNPs occurring outside protein Conserved Domains (CDs) of TET2, a recently discovered epigenetic regulator involved in leukemogenesis. Functional effects of TET2 gene variations were assessed with four publicly available tools: PhD-SNP, MutPred, PolyPhen-2 and SIFT. The methods were tested on the dataset of 166 SNPs and somatic TET2 mutations, and separately on the subset of 69 variations outside TET2 CDs. Abilities of tested tools to separate neutral SNPs from pathogenic mutations were similar to previously reported on complete TET2 dataset. However, we observed significantly lower accuracy of predictions outside CDs, ranging from 0.54 to 0.62. Also, areas under the ROC curves were low, 0.51-0.55. Correlations between predictions and positions of variations inside/outside CDs were significant and high, 0.46-0.78. Low efficiency of commonly used tools in predicting functional effects of variations outside CDs emphasize the need for new or modified algorithms.", journal = "2nd International Conference “Theoretical Approaches to Bioinformation Systems” (TABIS.2013), September 17-22, 2013, Belgrade, Serbia", title = "Can We Use Standard Tools to Predict Functional Effects of Missense Gene Variations Outside Conserved Domains? TET2 Example", pages = "65-71", url = "https://hdl.handle.net/21.15107/rcub_vinar_10771" }
Gemović, B. S., Perović, V. R., Glišić, S.,& Veljković, N. V.. (2014). Can We Use Standard Tools to Predict Functional Effects of Missense Gene Variations Outside Conserved Domains? TET2 Example. in 2nd International Conference “Theoretical Approaches to Bioinformation Systems” (TABIS.2013), September 17-22, 2013, Belgrade, Serbia, 65-71. https://hdl.handle.net/21.15107/rcub_vinar_10771
Gemović BS, Perović VR, Glišić S, Veljković NV. Can We Use Standard Tools to Predict Functional Effects of Missense Gene Variations Outside Conserved Domains? TET2 Example. in 2nd International Conference “Theoretical Approaches to Bioinformation Systems” (TABIS.2013), September 17-22, 2013, Belgrade, Serbia. 2014;:65-71. https://hdl.handle.net/21.15107/rcub_vinar_10771 .
Gemović, Branislava S., Perović, Vladimir R., Glišić, Sanja, Veljković, Nevena V., "Can We Use Standard Tools to Predict Functional Effects of Missense Gene Variations Outside Conserved Domains? TET2 Example" in 2nd International Conference “Theoretical Approaches to Bioinformation Systems” (TABIS.2013), September 17-22, 2013, Belgrade, Serbia (2014):65-71, https://hdl.handle.net/21.15107/rcub_vinar_10771 .