用Transformer模型预测空气颗粒物毒物与蛋白相互作用,找出潜在有害成分。
Transformer-based toxin-protein interaction analysis prioritizes airborne particulate matter components with potential adverse health effects
- 基于双预训练语言模型和交叉注意力机制,建模毒物与蛋白的复杂互作
- 实验验证可有效识别有毒成分与靶点蛋白的结合关系,提升预测精度
- 助力环境毒理研究,加速高风险污染物的筛选与健康影响评估
空气污染,尤其是空气颗粒物(PM),对全球公共卫生构成重大威胁。理解颗粒物相关毒物与其在人体内细胞靶点之间的关联,有助于揭示空气污染影响健康的机制,并建立因果关系。尽管已有大量研究探讨PM对健康的影响,但毒物与靶点关联的理解仍有限。我们开发了tipFormer(基于Transformer的毒物-蛋白相互作用预测工具),一种新型深度学习方法,用于识别能穿透人体细胞并引发病理性生物活动和信号级联反应的毒物成分。该模型采用双预训练语言模型编码蛋白质序列和化学分子,通过卷积编码器整合序列特征,并引入具有交叉注意力机制的学习模块,解码和阐明毒物与蛋白间复杂的相互作用。实验表明,tipFormer能有效捕捉毒物与蛋白间的相互作用。该方法为环境质量和毒理学研究人员提供了高通量识别与优先排序有害物质的能力,支持更精准的实验室研究与现场监测,最终深化对空气污染影响人类健康机制的理解。
原文摘要 · Abstract (English)
Air pollution, particularly airborne particulate matter (PM), poses a significant threat to public health globally. It is crucial to comprehend the association between PM-associated toxic components and their cellular targets in humans to understand the mechanisms by which air pollution impacts health and to establish causal relationships between air pollution and public health consequences. Although many studies have explored the impact of PM on human health, the understanding of the association between toxins and the associated targets remain limited. Leveraging cutting-edge deep learning technologies, we developed tipFormer (toxin-protein interaction prediction based on transformer), a novel deep-learning tool for identifying toxic components capable of penetrating human cells and instigating pathogenic biological activities and signaling cascades. Experimental results show that tipFormer effectively captures interactions between proteins and toxic components. It incorporates dual pre-trained language models to encode protein sequences and chemicals. It employs a convolutional encoder to assimilate the sequential attributes of proteins and chemicals. It then introduces a learning module with a cross-attention mechanism to decode and elucidate the multifaceted interactions pivotal for the hotspots binding proteins and chemicals. Experimental results show that tipFormer effectively captures interactions between proteins and toxic components. This approach offers significant value to air quality and toxicology researchers by allowing high-throughput identification and prioritization of hazards. It supports more targeted laboratory studies and field measurements, ultimately enhancing our understanding of how air pollution impacts human health.
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