Computational Method for Identifying Malonylation Sites by Using Random Forest Algorithm

As a newly uncovered post-translational modification on the ε-amino group of lysine residue, protein malonylation was found to be involved in metabolic pathways and certain diseases. Apart from experimental approaches, several computational methods based on machine learning algorithms were recently proposed to predict malonylation sites. However, previous methods failed to address imbalanced data sizes between positive and negative samples.

In this study, we identified the significant features of malonylation sites in a novel computational method which applied machine learning algorithms and balanced data sizes by applying synthetic minority over-sampling technique.

Four types of features, namely, amino acid (AA) composition, position-specific scoring matrix (PSSM), AA factor, and disorder were used to encode residues in protein segments. Then, a two-step feature selection procedure including maximum relevance minimum redundancy and incremental feature selection, together with random forest algorithm, was performed on the constructed hybrid feature vector.

An optimal classifier was built from the optimal feature subset, which featured an F1-measure of 0.356. Feature analysis was performed on several selected important features.

Results showed that certain types of PSSM and disorder features may be closely associated with malonylation of lysine residues. Our study contributes to the development of computational approaches for predicting malonyllysine and provides insights into molecular mechanism of malonylation.