Fang Jiwei, Fan Henghui, Zhao Jintao, Zhao Jianping, Xia Junfeng
College of Mathematics and System Science, Xinjiang University, Urumqi, Xinjiang, 830046, China.
Institutes of Physical Science and Information Technology, Anhui University, Hefei, 230601, China.
BMC Biol. 2025 Jul 1;23(1):170. doi: 10.1186/s12915-025-02273-0.
BACKGROUND: Multi-functional therapeutic peptides have emerged as promising candidates in drug development and disease diagnosis due to their biocompatibility, targeting capability, and low immunogenicity. However, the identification of peptide functions through wet-lab experiments is both time-consuming and costly, necessitating efficient computational prediction methods. The field faces challenges such as long-tail distribution problems, data sparsity, and complex label co-occurrence patterns due to peptides' multi-functional nature. RESULTS: To address these challenges, we propose AMCL, a novel framework for multi-functional therapeutic peptide prediction. AMCL incorporates a semantic-preserving data augmentation strategy, a multi-label supervised contrastive learning mechanism with hard sample mining, and a weighted combined loss combining Focal Dice Loss (FDL) and Distribution-Balanced Loss (DBL) to alleviate class imbalance issues. Additionally, we introduce a category-adaptive threshold selection mechanism for individual functional categories. The interpretability of AMCL is demonstrated through feature space analysis and Gradient-weighted Class Activation Mapping (Grad-CAM) visualization. CONCLUSIONS: Comprehensive experiments show that AMCL significantly outperforms existing methods across multiple key metrics, including Absolute true, Accuracy, Macro-F1, and Micro-F1, establishing a new state-of-the-art in therapeutic peptide multi-functional prediction.
背景:多功能治疗性肽因其生物相容性、靶向能力和低免疫原性,已成为药物开发和疾病诊断中颇具潜力的候选物。然而,通过湿实验室实验鉴定肽的功能既耗时又昂贵,因此需要高效的计算预测方法。由于肽的多功能性质,该领域面临长尾分布问题、数据稀疏性和复杂的标签共现模式等挑战。 结果:为应对这些挑战,我们提出了AMCL,一种用于多功能治疗性肽预测的新型框架。AMCL采用了语义保留数据增强策略、带有难样本挖掘的多标签监督对比学习机制,以及结合了焦点骰子损失(FDL)和分布平衡损失(DBL)的加权组合损失,以缓解类别不平衡问题。此外,我们还为各个功能类别引入了类别自适应阈值选择机制。通过特征空间分析和梯度加权类激活映射(Grad-CAM)可视化展示了AMCL的可解释性。 结论:全面的实验表明,AMCL在包括绝对真值、准确率、宏F1和微F1等多个关键指标上显著优于现有方法,在治疗性肽多功能预测方面建立了新的最先进水平。
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