iSuc-ChiDT: a computational method for identifying succinylation sites using statistical difference table encoding and the chi-square decision table classifier

Abstract

Background: Lysine succinylation is a type of protein post-translational modification which is widely involved in cell differentiation, cell metabolism and other important physiological activities. To study the molecular mechanism of succinylation in depth, succinylation sites need to be accurately identified, and because experimental approaches are costly and time-consuming, there is a great demand for reliable computational methods. Feature extraction is a key step in building succinylation site prediction models, and the development of effective new features improves predictive accuracy. Because the number of false succinylation sites far exceeds that of true sites, traditional classifiers perform poorly, and designing a classifier to effectively handle highly imbalanced datasets has always been a challenge.

Results: A new computational method, iSuc-ChiDT, is proposed to identify succinylation sites in proteins. In iSuc-ChiDT, chi-square statistical difference table encoding is developed to extract positional features, and has a higher predictive accuracy and fewer features compared to common position-based encoding schemes such as binary encoding and physicochemical property encoding. Single amino acid and undirected pair-coupled amino acid composition features are supplemented to improve the fault tolerance for residue insertions and deletions. After feature selection by Chi-MIC-share algorithm, the chi-square decision table (ChiDT) classifier is constructed for imbalanced classification. With a training set of 4748:50,551(true: false sites), ChiDT clearly outperforms traditional classifiers in predictive accuracy, and runs fast. Using an independent testing set of experimentally identified succinylation sites, iSuc-ChiDT achieves a sensitivity of 70.47%, a specificity of 66.27%, a Matthews correlation coefficient of 0.205, and a global accuracy index Q⁹ of 0.683, showing a significant improvement in sensitivity and overall accuracy compared to PSuccE, Success, SuccinSite, and other existing succinylation site predictors.

Conclusions: iSuc-ChiDT shows great promise in predicting succinylation sites and is expected to facilitate further experimental investigation of protein succinylation.

Keywords: Chi-square statistical difference table; ChiDT; Feature selection; Imbalanced dataset; Succinylation site.