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    The rational modification of siRNA molecules is crucial for ensuring their drug-like properties. Machine learning-based prediction of chemically modified siRNA (cm-siRNA) efficiency can significantly optimize the design process of siRNA chemical modifications, saving time and cost in siRNA drug development. However, existing in-silico methods suffer from limitations such as small datasets, inadequate data representation capabilities, and lack of interpretability. Therefore, in this study, we developed the Cm-siRPred algorithm based on a multi-view learning strategy. The algorithm employs a multi-view strategy to represent the double-strand sequences, chemical modifications, and physicochemical properties of cm-siRNA. It incorporates a cross-attention model to globally correlate different representation vectors and a two-layer CNN module to learn local correlation features. The algorithm demonstrates exceptional performance in cross-validation experiments, independent dataset, and case studies on approved siRNA drugs, and showcasing its robustness and generalization ability. In addition, we developed a user-friendly webserver that enables efficient prediction of cm-siRNA efficiency and assists in the design of siRNA drug chemical modifications. In summary, Cm-siRPred is a practical tool that offers valuable technical support for siRNA chemical modification and drug efficiency research, while effectively assisting in the development of novel small nucleic acid drugs. Cm-siRPred is freely available at https://cellknowledge.com.cn/sirnapredictor/. Copyright © 2024 Elsevier B.V. All rights reserved.

    Citation

    Tianyuan Liu, Junyang Huang, Delun Luo, Liping Ren, Lin Ning, Jian Huang, Hao Lin, Yang Zhang. Cm-siRPred: Predicting chemically modified siRNA efficiency based on multi-view learning strategy. International journal of biological macromolecules. 2024 Apr;264(Pt 2):130638

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    PMID: 38460652

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