title: Prediction of redox-sensitive cysteines using sequential distance and other sequence-based features.
abstract: BACKGROUND
  Reactive oxygen species can modify the structure and function of proteins and may also act as important signaling molecules in various cellular processes. Cysteine thiol groups of proteins are particularly susceptible to oxidation. Meanwhile, their reversible oxidation is of critical roles for redox regulation and signaling. Recently, several computational tools have been developed for predicting redox-sensitive cysteines; however, those methods either only focus on catalytic redox-sensitive cysteines in thiol oxidoreductases, or heavily depend on protein structural data, thus cannot be widely used.
  
  
  RESULTS
  In this study, we analyzed various sequence-based features potentially related to cysteine redox-sensitivity, and identified three types of features for efficient computational prediction of redox-sensitive cysteines. These features are: sequential distance to the nearby cysteines, PSSM profile and predicted secondary structure of flanking residues. After further feature selection using SVM-RFE, we developed Redox-Sensitive Cysteine Predictor (RSCP), a SVM based classifier for redox-sensitive cysteine prediction using primary sequence only. Using 10-fold cross-validation on RSC758 dataset, the accuracy, sensitivity, specificity, MCC and AUC were estimated as 0.679, 0.602, 0.756, 0.362 and 0.727, respectively. When evaluated using 10-fold cross-validation with BALOSCTdb dataset which has structure information, the model achieved performance comparable to current structure-based method. Further validation using an independent dataset indicates it is robust and of relatively better accuracy for predicting redox-sensitive cysteines from non-enzyme proteins.
  
  
  CONCLUSIONS
  In this study, we developed a sequence-based classifier for predicting redox-sensitive cysteines. The major advantage of this method is that it does not rely on protein structure data, which ensures more extensive application compared to other current implementations. Accurate prediction of redox-sensitive cysteines not only enhances our understanding about the redox sensitivity of cysteine, it may also complement the proteomics approach and facilitate further experimental investigation of important redox-sensitive cysteines.
authors.affiliation: State Key Laboratory of Agrobiotechnology and School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, People's Republic of China.
authors.forename: Ming-An
authors.initials: MA
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Agrobiotechnology and School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology and Genetics, School of Basic Medical Sciences, Shenzhen University Health Science Center, Nanhai Ave 3688, Shenzhen, 518060, People's Republic of China.
authors.forename: Yejun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Taipa, Macau, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ge
authors.affiliation: State Key Laboratory of Agrobiotechnology and School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, People's Republic of China. djguo@cuhk.edu.hk.
authors.forename: Dianjing
authors.initials: D
authors.lastname: Guo
mesh_terms: D003545:Cysteine / Q000737:chemistry*; D010084:Oxidation-Reduction; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry; D020539:Sequence Analysis, Protein / Q000379:methods*; D060388:Support Vector Machine
chemical_list: D011506:Proteins; D003545:Cysteine
keywords: Post-translational modification; Reactive oxygen species; Redox-sensitive cysteine; SVM-based recursive feature elimination; Support vector machine