arXiv:2509.24262q-bio.QMcs.AI2025-09

用注意力机制区分蛋白的核酸结合特异性,提升多标签预测准确率。

LAMP-PRo: Label-aware Attention for Multi-label Prediction of DNA- and RNA-binding Proteins using Protein Language Models

  • 基于PLM和标签感知注意力,动态捕捉每类结合特征。
  • 在iDRBP-MMC数据集上,DRBP预测F1达0.87,优于现有方法。
  • 可视化展示关键序列区域,适合生物信息学研究者使用。

识别DNA结合蛋白(DBPs)和RNA结合蛋白(RBPs)对理解细胞功能、分子互作及调控机制至关重要。由于两者高度相似,现有方法常出现交叉预测错误,且难以识别同时结合DNA和RNA的双功能蛋白(DRBPs)。为此,本文提出LAMP-PRo框架,基于预训练蛋白语言模型(PLM,如ESM-2)、注意力机制与多标签学习解决上述问题。首先利用ESM-2对蛋白序列进行嵌入,再通过卷积神经网络提取特征;随后采用多头自注意力捕获上下文信息,并引入标签感知注意力,为每类标签(DBP、RBP、非核酸结合蛋白)生成特定表示;进一步设计跨标签注意力机制,显式建模DBP与RBP间的依赖关系,提升DRBP预测精度;最终通过线性层加Sigmoid完成多标签输出。大量实验表明,该模型在iDRBP-MMC数据集上表现优异,尤其在DRBP预测中达到F1=0.87,显著优于现有方法。此外,模型具备良好可解释性,支持可视化关键序列区域。原始数据集链接:http://bliulab.net/iDRBP_MMC,代码开源地址:https://github.com/NimishaGhosh/LAMP-PRo。

原文摘要 · Abstract (English)

Identifying DNA- (DBPs) and RNA-binding proteins (RBPs) is crucial for the understanding of cell function, molecular interactions as well as regulatory functions. Owing to their high similarity, most of the existing approaches face challenges in differentiating between DBPs and RBPs leading to high cross-prediction errors. Moreover, identifying proteins which bind to both DNA and RNA (DRBPs) is also quite a challenging task. In this regard, we propose a novel framework viz. LAMP-PRo which is based on pre-trained protein language model (PLM), attention mechanisms and multi-label learning to mitigate these issues. First, pre-trained PLM such ESM-2 is used for embedding the protein sequences followed by convolutional neural network (CNN). Subsequently multi-head self-attention mechanism is applied for the contextual information while label-aware attention is used to compute class-specific representations by attending to the sequence in a way that is tailored to each label (DBP, RBP and non-NABP) in a multi-label setup. We have also included a novel cross-label attention mechanism to explicitly capture dependencies between DNA- and RNA-binding proteins, enabling more accurate prediction of DRBP. Finally, a linear layer followed by a sigmoid function are used for the final prediction. Extensive experiments are carried out to compare LAMP-PRo with the existing methods wherein the proposed model shows consistent competent performance. Furthermore, we also provide visualization to showcase model interpretability, highlighting which parts of the sequence are most relevant for a predicted label. The original datasets are available at http://bliulab.net/iDRBP\_MMC and the codes are available at https://github.com/NimishaGhosh/LAMP-PRo.

蛋白语言模型多标签预测核酸结合注意力机制

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