arXiv:2506.13485q-bio.BMcs.LG2025-06ICML被引 3

用课程学习提升肽序列预测准确率,训练失败率降90%以上

Curriculum Learning for Biological Sequence Prediction: The Case of De Novo Peptide Sequencing

  • 按模型能力动态调整肽序列难易度,从简单到复杂逐步训练
  • 在九个物种上超越此前所有方法,显著降低训练失败率
  • 推理时自迭代优化,提升序列精度,适合高要求蛋白组学研究

肽序列预测——从质谱数据中识别氨基酸序列——是蛋白质组学中的基础任务。非自回归变压器(NAT)已证明在此任务上表现优异,优于传统方法。与逐个生成词元的自回归模型不同,NAT通过未掩码的双向注意力同时预测所有位置。然而,现有NAT方法多依赖连接时序分类(CTC)损失,因其复杂性带来显著优化挑战,并增加训练失败风险。为此,我们提出一种改进的非自回归肽序列预测模型,引入结构化蛋白质序列课程学习策略。该策略通过采样过程,根据模型对肽生成能力的估计动态调整学习难度,实现从简单到复杂的渐进式学习。此外,我们设计了一个推理时自精炼模块,利用学习到的NAT词元嵌入进行迭代优化,提升序列预测的细粒度准确性。基于多种数据分布的采样训练表明,该课程学习策略使NAT训练失败频率降低超过90%。在九个基准物种上的评估显示,本方法在多个指标和物种上均优于此前所有方法。

原文摘要 · Abstract (English)

Peptide sequencing-the process of identifying amino acid sequences from mass spectrometry data-is a fundamental task in proteomics. Non-Autoregressive Transformers (NATs) have proven highly effective for this task, outperforming traditional methods. Unlike autoregressive models, which generate tokens sequentially, NATs predict all positions simultaneously, leveraging bidirectional context through unmasked self-attention. However, existing NAT approaches often rely on Connectionist Temporal Classification (CTC) loss, which presents significant optimization challenges due to CTC's complexity and increases the risk of training failures. To address these issues, we propose an improved non-autoregressive peptide sequencing model that incorporates a structured protein sequence curriculum learning strategy. This approach adjusts protein's learning difficulty based on the model's estimated protein generational capabilities through a sampling process, progressively learning peptide generation from simple to complex sequences. Additionally, we introduce a self-refining inference-time module that iteratively enhances predictions using learned NAT token embeddings, improving sequence accuracy at a fine-grained level. Our curriculum learning strategy reduces NAT training failures frequency by more than 90% based on sampled training over various data distributions. Evaluations on nine benchmark species demonstrate that our approach outperforms all previous methods across multiple metrics and species.

肽序列预测课程学习非自回归蛋白质组学

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