EnsembleGASVR: A novel ensemble method for classifying missense single nucleotide polymorphisms

Trisevgeni Rapakoulia, Konstantinos A. Theofilatos, Dimitrios A. Kleftogiannis, Spiridon D. Likothanasis, Athanasios K. Tsakalidis, Seferina P. Mavroudi

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Motivation: Single nucleotide polymorphisms (SNPs) are considered the most frequently occurring DNA sequence variations. Several computational methods have been proposed for the classification of missense SNPs to neutral and disease associated. However, existing computational approaches fail to select relevant features by choosing them arbitrarily without sufficient documentation. Moreover, they are limited to the problem ofmissing values, imbalance between the learning datasets and most of them do not support their predictions with confidence scores. Results: To overcome these limitations, a novel ensemble computational methodology is proposed. EnsembleGASVR facilitates a twostep algorithm, which in its first step applies a novel evolutionary embedded algorithm to locate close to optimal Support Vector Regression models. In its second step, these models are combined to extract a universal predictor, which is less prone to overfitting issues, systematizes the rebalancing of the learning sets and uses an internal approach for solving the missing values problem without loss of information. Confidence scores support all the predictions and the model becomes tunable by modifying the classification thresholds. An extensive study was performed for collecting the most relevant features for the problem of classifying SNPs, and a superset of 88 features was constructed. Experimental results show that the proposed framework outperforms well-known algorithms in terms of classification performance in the examined datasets. Finally, the proposed algorithmic framework was able to uncover the significant role of certain features such as the solvent accessibility feature, and the top-scored predictions were further validated by linking them with disease phenotypes. © The Author 2014.
Original languageEnglish (US)
Pages (from-to)2324-2333
Number of pages10
Issue number16
StatePublished - Apr 26 2014

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: Funding: Trisevgeni Rapakoulia and Dimitrios Kleftogiannis were supported by the King Abdullah University of Science and Technology (KAUST).

ASJC Scopus subject areas

  • Biochemistry
  • Computational Theory and Mathematics
  • Computational Mathematics
  • Molecular Biology
  • Statistics and Probability
  • Computer Science Applications


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