ProMethylNet: Protein Methylation Site Prediction Based on Multimodal Feature Fusion and Deep Learning

Protein methylation is a fundamental post-translational modification (PTM) that plays critical roles in gene regulation, protein interactions, and cellular signaling pathways. However, traditional experimental approaches for identifying methylation sites are time-consuming, labor-intensive, and limited in throughput. Therefore, there is an urgent need for computational methods that efficiently and accurately predict methylation sites. In this study, we introduce ProMethylNet, a deep learning framework designed for predicting protein methylation sites. ProMethylNet integrates multimodal features, including one-hot encoding, amino acid physicochemical properties, ProtBERT embeddings, and position-specific scoring matrices(PSSM), to enrich sequence representation. The framework incorporates multi-scale convolutional attention networks(MSCANet), graph attention networks(GAT), and bidirectional long short-term memory networks(BiLSTM), effectively capturing local sequence motifs, structural information, and long-range dependencies within protein sequences. To mitigate the issue of class imbalance in the dataset, ProMethylNet incorporates a weighted binary cross-entropy loss function during training. External validation on an independent subset(20%) of the UniProtKB dataset and the PLMD 3.0 dataset indicates that ProMethylNet achieves notable improvements over existing methods in F1-score, Matthews correlation coefficient(MCC), and area under the curve(AUC), with an approximate increase of 20 percentage points. These results suggest that ProMethylNet demonstrates a certain level of robustness and efficiency, indicating its potential applicability in protein methylation site prediction, functional annotation, and broader biomedical research.

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Journal
IEEE Transactions on Computational Biology and Bioinformatics
Published
2025-06-02
DOI
https://doi.org/10.1109/tcbbio.2025.3575783
Primary Topic
Topic Modeling
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article
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article

ProMethylNet: Protein Methylation Site Prediction Based on Multimodal Feature Fusion and Deep Learning

Xinyi Qin, Shoubo Feng, Xueyun Cheng, Lu Zhang et al.
IEEE Transactions on Computational Biology and Bioinformatics
Topic Modeling
article

ProMethylNet: Protein Methylation Site Prediction Based on Multimodal Feature Fusion and Deep Learning

Xinyi Qin, Shoubo Feng, Xueyun Cheng, Lu Zhang, Yijun Wang, Cui Dai
article en

Abstract

Protein methylation is a fundamental post-translational modification (PTM) that plays critical roles in gene regulation, protein interactions, and cellular signaling pathways. However, traditional experimental approaches for identifying methylation sites are time-consuming, labor-intensive, and limited in throughput. Therefore, there is an urgent need for computational methods that efficiently and accurately predict methylation sites. In this study, we introduce ProMethylNet, a deep learning framework designed for predicting protein methylation sites. ProMethylNet integrates multimodal features, including one-hot encoding, amino acid physicochemical properties, ProtBERT embeddings, and position-specific scoring matrices(PSSM), to enrich sequence representation. The framework incorporates multi-scale convolutional attention networks(MSCANet), graph attention networks(GAT), and bidirectional long short-term memory networks(BiLSTM), effectively capturing local sequence motifs, structural information, and long-range dependencies within protein sequences. To mitigate the issue of class imbalance in the dataset, ProMethylNet incorporates a weighted binary cross-entropy loss function during training. External validation on an independent subset(20%) of the UniProtKB dataset and the PLMD 3.0 dataset indicates that ProMethylNet achieves notable improvements over existing methods in F1-score, Matthews correlation coefficient(MCC), and area under the curve(AUC), with an approximate increase of 20 percentage points. These results suggest that ProMethylNet demonstrates a certain level of robustness and efficiency, indicating its potential applicability in protein methylation site prediction, functional annotation, and broader biomedical research.

IEEE Transactions on Computational Biology and BioinformaticsVol. 22(4)
Shanxi University (CN), Nantong University (CN), Nanjing University of Information Science and Technology (CN), Nanjing University of Science and Technology (CN)
Zero hunger
Openalex Percentile: Top 94%
Topic Modeling
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