Single amino acid variations (SAVs) potentially alter biological functions, including causing diseases or natural differences between individuals. Identifying the relationship between a SAV and certain disease provides the starting point for understanding the underlying mechanisms of specific associations, and can help further prevention and diagnosis of inherited disease.We propose PredSAV, a computational method that can effectively predict how likely SAVs are to be associated with disease by incorporating gradient tree boosting (GTB) algorithm and optimally selected neighborhood features. A two-step feature selection approach is used to explore the most relevant and informative neighborhood properties that contribute to the prediction of disease association of SAVs across a wide range of sequence and structural features, especially some novel structural neighborhood features. In cross-validation experiments on the benchmark dataset, PredSAV achieves promising performances with an AUC score of 0.908 and a specificity of 0.838, which are significantly better than that of the other existing methods. Furthermore, we validate the capability of our proposed method by an independent test and gain a competitive advantage as a result. PredSAV, which combines gradient tree boosting with optimally selected neighborhood features, can return reliable predictions in distinguishing between disease-associated and neutral variants. Compared with existing methods, PredSAV shows improved specificity as well as increased overall performance.
Pan, Y., Liu, D., & Deng, L. (2017). Accurate prediction of functional effects for variants by combining gradient tree boosting with optimal neighborhood properties. PLoS ONE, 12(6). https://doi.org/10.1371/journal.pone.0179314