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PRITrans:一种基于 Transformer 的方法,用于预测错义突变对蛋白质 - RNA 相互作用的影响。

PRITrans: A Transformer-Based Approach for the Prediction of the Effects of Missense Mutation on Protein-RNA Interactions.

机构信息

State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan, Nanjing 210023, China.

School of Computer, Jiangsu University of Science and Technology, 666 Changhui Road, Zhenjiang 212100, China.

出版信息

Int J Mol Sci. 2024 Nov 17;25(22):12348. doi: 10.3390/ijms252212348.

Abstract

Protein-RNA interactions are essential to many cellular functions, and missense mutations in RNA-binding proteins can disrupt these interactions, often leading to disease. To address this, we developed PRITrans, a specialized computational method aimed at predicting the effects of missense mutations on protein-RNA interactions, which is vital for understanding disease mechanisms and advancing molecular biology research. PRITrans is a novel deep learning model designed to predict the effects of missense mutations on protein-RNA interactions, which employs a Transformer architecture enhanced with multiscale convolution modules for comprehensive feature extraction. Its primary innovation lies in integrating protein language model embeddings with a deep feature fusion strategy, effectively handling high-dimensional feature representations. By utilizing multi-layer self-attention mechanisms, PRITrans captures nuanced, high-level sequence information, while multiscale convolutions extract features across various depths, thereby enhancing predictive accuracy. Consequently, this architecture enables significant improvements in ΔΔG prediction compared to traditional approaches. We validated PRITrans using three different cross-validation strategies on two newly reconstructed mutation datasets, S315 and S630 (containing 315 forward and 315 reverse mutations). The results consistently demonstrated PRITrans's strong performance on both datasets. PRITrans demonstrated strong predictive capability, achieving a Pearson correlation coefficient of 0.741 and a root mean square error (RMSE) of 1.168 kcal/mol on the S630 dataset. Moreover, its robust performance extended to independent test sets, achieving a Pearson correlation of 0.699 and an RMSE of 1.592 kcal/mol. These results underscore PRITrans's potential as a powerful tool for protein-RNA interaction studies. Moreover, when tested against existing prediction methods on an independent dataset, PRITrans showed improved predictive accuracy and robustness.

摘要

蛋白质与 RNA 的相互作用对于许多细胞功能至关重要,而 RNA 结合蛋白中的错义突变会破坏这些相互作用,从而导致疾病。为了解决这个问题,我们开发了 PRITrans,这是一种专门的计算方法,旨在预测错义突变对蛋白质与 RNA 相互作用的影响,这对于理解疾病机制和推进分子生物学研究至关重要。PRITrans 是一种新的深度学习模型,旨在预测错义突变对蛋白质与 RNA 相互作用的影响,它采用了带有多尺度卷积模块的 Transformer 架构,用于全面的特征提取。它的主要创新在于将蛋白质语言模型嵌入与深度特征融合策略相结合,有效地处理高维特征表示。通过利用多层自注意力机制,PRITrans 捕获了细微的、高级的序列信息,而多尺度卷积则提取了各种深度的特征,从而提高了预测准确性。因此,与传统方法相比,该架构在 ΔΔG 预测方面有了显著的改进。我们使用三种不同的交叉验证策略在两个新重建的突变数据集 S315 和 S630 上(分别包含 315 个正向和 315 个反向突变)验证了 PRITrans。结果一致表明 PRITrans 在两个数据集上都具有出色的性能。PRITrans 表现出强大的预测能力,在 S630 数据集上的 Pearson 相关系数为 0.741,均方根误差(RMSE)为 1.168 kcal/mol。此外,其稳健的性能扩展到了独立的测试集,Pearson 相关系数为 0.699,RMSE 为 1.592 kcal/mol。这些结果突出了 PRITrans 作为蛋白质与 RNA 相互作用研究的有力工具的潜力。此外,当在独立数据集上与现有的预测方法进行测试时,PRITrans 表现出了更高的预测准确性和稳健性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c62/11594650/4a4f8af75f3e/ijms-25-12348-g001.jpg

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