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iACP-DFSRA:基于 ResCNN 和注意力的双通道融合策略的抗癌肽鉴定。

iACP-DFSRA: Identification of Anticancer Peptides Based on a Dual-channel Fusion Strategy of ResCNN and Attention.

机构信息

School of Science, Dalian Maritime University, Dalian 116026, China.

School of Science, Dalian Maritime University, Dalian 116026, China.

出版信息

J Mol Biol. 2024 Nov 15;436(22):168810. doi: 10.1016/j.jmb.2024.168810. Epub 2024 Oct 1.

Abstract

Anticancer peptides (ACPs) have been widely applied in the treatment of cancer owing to good safety, rational side effects, and high selectivity. However, the number of ACPs that have been experimentally validated is limited as identification of ACPs is extremely expensive. Hence, accurate and cost-effective identification methods for ACPs are urgently needed. In this work, we proposed a deep learning-based model, named iACP-DFSRA, for ACPs identification. Specifically, we adopted two kinds of sequence embedding technologies, ProtBert_BFD pre-training language model and handcrafted features to encode protein sequences. Then, the LightGBM was used for feature selection, and the selected features were input into ResCNN and Attention mechanism, respectively, to extract local and global features. Finally, the concatenate features were deeply fused by using the Attention mechanism to allow key features to be paid more attention to by the model and make predictions by fully connected layer. The results of 10-fold cross-validation demonstrated that the iACP-DFSRA model delivered improved results in most metrics with Sp of 94.15%, Sn of 95.32%, Acc of 94.74% and MCC of 89.48% compared to the latest AACFlow model. Indeed, the iACP-DFSRA model is the only model with Acc > 90% and MCC > 80% on this independent test dataset. Furthermore, we have further demonstrated the superiority of our model on additional datasets. In addition, t-SNE and SHAP interpretation analysis demonstrated that it is crucial to use two channels for feature extraction and use the Attention mechanism for deep fusion, which helps the iACP-DFSRA to predict ACPs more effectively.

摘要

抗癌肽 (ACPs) 由于安全性好、副作用合理、选择性高,已广泛应用于癌症治疗。然而,由于鉴定 ACPs 的成本极高,经过实验验证的 ACPs 数量有限。因此,迫切需要准确且具有成本效益的 ACPs 鉴定方法。在这项工作中,我们提出了一种基于深度学习的模型,称为 iACP-DFSRA,用于 ACPs 的鉴定。具体来说,我们采用了两种序列嵌入技术,ProtBert_BFD 预训练语言模型和手工制作的特征来编码蛋白质序列。然后,使用 LightGBM 进行特征选择,选择的特征分别输入到 ResCNN 和 Attention 机制中,以提取局部和全局特征。最后,通过使用 Attention 机制对拼接特征进行深度融合,使模型更加关注关键特征,并通过全连接层进行预测。10 折交叉验证的结果表明,与最新的 AACFlow 模型相比,iACP-DFSRA 模型在大多数指标上都有了改进,Sp 为 94.15%,Sn 为 95.32%,Acc 为 94.74%,MCC 为 89.48%。事实上,在这个独立的测试数据集上,iACP-DFSRA 模型是唯一的 Acc>90%和 MCC>80%的模型。此外,我们还进一步在其他数据集上验证了我们模型的优越性。此外,t-SNE 和 SHAP 解释分析表明,使用两个通道进行特征提取和使用 Attention 机制进行深度融合是至关重要的,这有助于 iACP-DFSRA 更有效地预测 ACPs。

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