Fang Yitian, Xu Fan, Wei Lesong, Jiang Yi, Chen Jie, Wei Leyi, Wei Dong-Qing
School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, China.
Peng Cheng Laboratory, Shenzhen, Guangdong 518055, China.
Brief Bioinform. 2023 Jan 19;24(1). doi: 10.1093/bib/bbac606.
Recently, peptide-based drugs have gained unprecedented interest in discovering and developing antifungal drugs due to their high efficacy, broad-spectrum activity, low toxicity and few side effects. However, it is time-consuming and expensive to identify antifungal peptides (AFPs) experimentally. Therefore, computational methods for accurately predicting AFPs are highly required. In this work, we develop AFP-MFL, a novel deep learning model that predicts AFPs only relying on peptide sequences without using any structural information. AFP-MFL first constructs comprehensive feature profiles of AFPs, including contextual semantic information derived from a pre-trained protein language model, evolutionary information, and physicochemical properties. Subsequently, the co-attention mechanism is utilized to integrate contextual semantic information with evolutionary information and physicochemical properties separately. Extensive experiments show that AFP-MFL outperforms state-of-the-art models on four independent test datasets. Furthermore, the SHAP method is employed to explore each feature contribution to the AFPs prediction. Finally, a user-friendly web server of the proposed AFP-MFL is developed and freely accessible at http://inner.wei-group.net/AFPMFL/, which can be considered as a powerful tool for the rapid screening and identification of novel AFPs.
近年来,基于肽的药物因其高效、广谱活性、低毒性和副作用少等特点,在抗真菌药物的发现和开发方面引起了前所未有的关注。然而,通过实验鉴定抗真菌肽(AFP)既耗时又昂贵。因此,迫切需要能够准确预测AFP的计算方法。在这项工作中,我们开发了AFP-MFL,这是一种新型深度学习模型,仅依靠肽序列来预测AFP,而不使用任何结构信息。AFP-MFL首先构建AFP的综合特征概况,包括从预训练的蛋白质语言模型中获得的上下文语义信息、进化信息和物理化学性质。随后,利用协同注意力机制分别将上下文语义信息与进化信息和物理化学性质进行整合。大量实验表明,AFP-MFL在四个独立测试数据集上优于现有模型。此外,采用SHAP方法探究每个特征对AFP预测的贡献。最后,开发了一个用户友好的AFP-MFL网络服务器,可通过http://inner.wei-group.net/AFPMFL/免费访问,它可被视为快速筛选和鉴定新型AFP的强大工具。