CarSite-II: an integrated classification algorithm for identifying carbonylated sites based on K-means similarity-based undersampling and synthetic minority oversampling techniques

Yun Zuo,Jianyuan Lin,Quan Zou,Xiangrong Liu,Xiangxiang Zeng

doi:10.1186/s12859-021-04134-3

Abstract

BackgroundCarbonylation is a non-enzymatic irreversible protein post-translational modification, and refers to the side chain of amino acid residues being attacked by reactive oxygen species and finally converted into carbonyl products. Studies have shown that protein carbonylation caused by reactive oxygen species is involved in the etiology and pathophysiological processes of aging, neurodegenerative diseases, inflammation, diabetes, amyotrophic lateral sclerosis, Huntington’s disease, and tumor. Current experimental approaches used to predict carbonylation sites are expensive, time-consuming, and limited in protein processing abilities. Computational prediction of the carbonylation residue location in protein post-translational modifications enhances the functional characterization of proteins.ResultsIn this study, an integrated classifier algorithm, CarSite-II, was developed to identify K, P, R, and T carbonylated sites. The resampling method K-means similarity-based undersampling and the synthetic minority oversampling technique (SMOTE-KSU) were incorporated to balance the proportions of K, P, R, and T carbonylated training samples. Next, the integrated classifier system Rotation Forest uses “support vector machine” subclassifications to divide three types of feature spaces into several subsets. CarSite-II gained Matthew’s correlation coefficient (MCC) values of 0.2287/0.3125/0.2787/0.2814, False Positive rate values of 0.2628/0.1084/0.1383/0.1313, False Negative rate values of 0.2252/0.0205/0.0976/0.0608 for K/P/R/T carbonylation sites by tenfold cross-validation, respectively. On our independent test dataset, CarSite-II yield MCC values of 0.6358/0.2910/0.4629/0.3685, False Positive rate values of 0.0165/0.0203/0.0188/0.0094, False Negative rate values of 0.1026/0.1875/0.2037/0.3333 for K/P/R/T carbonylation sites. The results show that CarSite-II achieves remarkably better performance than all currently available prediction tools.ConclusionThe related results revealed that CarSite-II achieved better performance than the currently available five programs, and revealed the usefulness of the SMOTE-KSU resampling approach and integration algorithm. For the convenience of experimental scientists, the web tool of CarSite-II is available in http://47.100.136.41:8081/

Highlights

Carbonylation is a non-enzymatic irreversible protein post-translational modification, and refers to the side chain of amino acid residues being attacked by reactive oxygen species and converted into carbonyl products
Protein carbonylation is an irreversible chemical modification in oxidative stress, which refers to the side chain of amino acid residues being attacked by reactive oxygen species and converted into carbonyl products [1]
Balance the training dataset and select optimal parameters of distance-based residue (DR) and rotation forest As described in Material and methods, each sequence in the training dataset can be encoded by DR, and synthetic minority oversampling technique (SMOTE) oversampling and K-means similarity-based undersampling (KSU) undersampling were used to resample the training dataset to make the same size of positive and negative training samples

Summary

Introduction

Carbonylation is a non-enzymatic irreversible protein post-translational modification, and refers to the side chain of amino acid residues being attacked by reactive oxygen species and converted into carbonyl products. Studies have shown that protein carbonylation caused by reactive oxygen species is involved in the etiology and pathophysiological processes of aging, neurodegenerative diseases, inflammation, diabetes, amyotrophic lateral sclerosis, Huntington’s disease, and tumor. Protein carbonylation is an irreversible chemical modification in oxidative stress, which refers to the side chain of amino acid residues being attacked by reactive oxygen species and converted into carbonyl products [1]. Studies have shown that protein carbonylation caused by reactive oxygen species is involved in the etiology and pathophysiological processes of aging, apoptosis and various neurodegenerative diseases. The β-actin carbonylation level of another cytoskeleton molecule increased in Alzheimer’s disease [4] and multiple sclerosis [2], but decreased in aging

Methods

Results

Discussion

Conclusion