AUTHOR=Luo Zhengtao , Wang Qingyong , Xia Yingchun , Zhu Xiaolei , Yang Shuai , Xu Zhaochun , Gu Lichuan TITLE=DLBWE-Cys: a deep-learning-based tool for identifying cysteine S-carboxyethylation sites using binary-weight encoding JOURNAL=Frontiers in Genetics VOLUME=Volume 15 - 2024 YEAR=2025 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1464976 DOI=10.3389/fgene.2024.1464976 ISSN=1664-8021 ABSTRACT=Cysteine S-carboxyethylation, a novel post-translational modification (PTM), plays a critical role in the pathogenesis of autoimmune diseases, particularly ankylosing spondylitis. Accurate identification of S-carboxyethylation modification sites is essential for elucidating their functional mechanisms. Unfortunately, there are currently no computational tools that can accurately predict these sites, posing a significant challenge to this area of research. In this study, we developed a new deep learning model, DLBWE-Cys, which integrates CNN, BiLSTM, Bahdanau attention mechanisms, and a fully connected neural network (FNN), using Binary-Weight encoding specifically designed for the accurate identification of cysteine S-carboxyethylation sites. Our experimental results show that our model architecture outperforms other machine learning and deep learning models in 5-fold cross-validation and independent testing. Feature comparison experiments confirmed the superiority of our proposed Binary-Weight encoding method over other encoding techniques. t-SNE visualization further validated the model’s effective classification capabilities. Additionally, we confirmed the similarity between the distribution of positional weights in our Binary-Weight encoding and the allocation of weights in attentional mechanisms. Further experiments proved the effectiveness of our Binary-Weight encoding approach. Thus, this model paves the way for predicting cysteine S-carboxyethylation modification sites in protein sequences. The source code of DLBWE-Cys and experiments data are available at: https://github.com/ztLuo-bioinfo/DLBWE-Cys.