{"title":"ILYCROsite: Identification of lysine crotonylation sites based on FCM-GRNN undersampling technique","authors":"","doi":"10.1016/j.compbiolchem.2024.108212","DOIUrl":null,"url":null,"abstract":"<div><p>Protein lysine crotonylation is an important post-translational modification that regulates various cellular activities. For example, histone crotonylation affects chromatin structure and promotes histone replacement. Identification and understanding of lysine crotonylation sites is crucial in the field of protein research. However, due to the increasing amount of non-histone crotonylation sites, existing classifiers based on traditional machine learning may encounter performance limitations. In order to address this problem, a novel deep learning-based model for identifying crotonylation sites is presented in this study, given the unique advantages of deep learning techniques for sequence data analysis. In this study, an MLP-Attention-based model was developed for the identification of crotonylation sites. Firstly, three feature extraction strategies, namely Amino Acid Composition, K-mer, and Distance-based residue features extraction strategy, were used to encode crotonylated and non-crotonylated sequences. Then, in order to balance the training dataset, the FCM-GRNN undersampling algorithm combining fuzzy clustering and generalized neural network approaches was introduced. Finally, to improve the effectiveness of crotonylation site identification, we explored various classification algorithms, and based on the relevant experimental performance comparisons, the multilayer perceptron (MLP) combined with the superimposed self-attention mechanism was finally selected to construct the prediction model ILYCROsite. The results obtained from independent testing and five-fold cross-validation demonstrated that the model proposed in this study, ILYCROsite, had excellent performance. Notably, on the independent test set, ILYCROsite achieves an AUC value of 87.93 %, which is significantly better than the existing state-of-the-art models. In addition, SHAP (Shapley Additive exPlanations) values were used to analyze the importance of features and their impact on model predictions. Meanwhile, in order to facilitate researchers to use the prediction model constructed in this study, we developed a prediction program to identify the crotonylation sites in a given protein sequence. The data and code for this program are available at: <span><span>https://github.com/wmqskr/ILYCROsite</span><svg><path></path></svg></span>.</p></div>","PeriodicalId":10616,"journal":{"name":"Computational Biology and Chemistry","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Computational Biology and Chemistry","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1476927124002007","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Protein lysine crotonylation is an important post-translational modification that regulates various cellular activities. For example, histone crotonylation affects chromatin structure and promotes histone replacement. Identification and understanding of lysine crotonylation sites is crucial in the field of protein research. However, due to the increasing amount of non-histone crotonylation sites, existing classifiers based on traditional machine learning may encounter performance limitations. In order to address this problem, a novel deep learning-based model for identifying crotonylation sites is presented in this study, given the unique advantages of deep learning techniques for sequence data analysis. In this study, an MLP-Attention-based model was developed for the identification of crotonylation sites. Firstly, three feature extraction strategies, namely Amino Acid Composition, K-mer, and Distance-based residue features extraction strategy, were used to encode crotonylated and non-crotonylated sequences. Then, in order to balance the training dataset, the FCM-GRNN undersampling algorithm combining fuzzy clustering and generalized neural network approaches was introduced. Finally, to improve the effectiveness of crotonylation site identification, we explored various classification algorithms, and based on the relevant experimental performance comparisons, the multilayer perceptron (MLP) combined with the superimposed self-attention mechanism was finally selected to construct the prediction model ILYCROsite. The results obtained from independent testing and five-fold cross-validation demonstrated that the model proposed in this study, ILYCROsite, had excellent performance. Notably, on the independent test set, ILYCROsite achieves an AUC value of 87.93 %, which is significantly better than the existing state-of-the-art models. In addition, SHAP (Shapley Additive exPlanations) values were used to analyze the importance of features and their impact on model predictions. Meanwhile, in order to facilitate researchers to use the prediction model constructed in this study, we developed a prediction program to identify the crotonylation sites in a given protein sequence. The data and code for this program are available at: https://github.com/wmqskr/ILYCROsite.
期刊介绍:
Computational Biology and Chemistry publishes original research papers and review articles in all areas of computational life sciences. High quality research contributions with a major computational component in the areas of nucleic acid and protein sequence research, molecular evolution, molecular genetics (functional genomics and proteomics), theory and practice of either biology-specific or chemical-biology-specific modeling, and structural biology of nucleic acids and proteins are particularly welcome. Exceptionally high quality research work in bioinformatics, systems biology, ecology, computational pharmacology, metabolism, biomedical engineering, epidemiology, and statistical genetics will also be considered.
Given their inherent uncertainty, protein modeling and molecular docking studies should be thoroughly validated. In the absence of experimental results for validation, the use of molecular dynamics simulations along with detailed free energy calculations, for example, should be used as complementary techniques to support the major conclusions. Submissions of premature modeling exercises without additional biological insights will not be considered.
Review articles will generally be commissioned by the editors and should not be submitted to the journal without explicit invitation. However prospective authors are welcome to send a brief (one to three pages) synopsis, which will be evaluated by the editors.