用轻量卷积+梯度提升融合基因序列与特征,精准预测抗生素耐药性。
Fusing Sequence Motifs and Pan-Genomic Features: Antimicrobial Resistance Prediction using an Explainable Lightweight 1D CNN-XGBoost Ensemble
- 设计轻量1D CNN捕捉SNP序列模式,结合XGBoost处理非局部特征交互。
- 在809株大肠杆菌数据上,环丙沙星预测MCC达0.926,庆大霉素F1-score为0.691。
- 模型聚焦已知耐药基因区段,具备可解释性,适合临床耐药性快速筛查。
抗生素耐药性(AMR)是日益严峻的全球健康危机。尽管基因组测序可实现耐药表型的快速预测,现有计算方法仍存局限:标准机器学习将基因组视为无序特征集合,忽略单核苷酸多态性(SNP)的序列上下文;而先进序列模型如Transformer通常需大量数据且计算成本高,不适用于本领域典型的中等规模数据集。为此,我们提出AMR-EnsembleNet,一种融合序列与特征学习的集成框架。构建轻量级定制1D卷积神经网络(CNN),高效从高维SNP数据中学习预测性序列基序;该序列感知模型与擅长捕捉复杂非局部特征交互的XGBoost模型集成。在包含809株大肠杆菌的基准数据集上训练评估,预测四种抗生素的耐药性,存在不同程度类别不平衡。我们的1D CNN-XGBoost集成在所有抗生素上均表现优异,环丙沙星(CIP)预测的马修斯相关系数(MCC)达0.926,庆大霉素(GEN)预测的宏平均F1-score最高,为0.691。此外,模型始终关注fusA和parC等已知耐药基因中的SNP,验证其学习到正确的遗传信号。研究表明,将序列感知1D CNN与基于特征的XGBoost模型结合,可有效克服单一模型的局限性,构建强大且可解释的预测系统。
原文摘要 · Abstract (English)
Antimicrobial Resistance (AMR) is a rapidly escalating global health crisis. While genomic sequencing enables rapid prediction of resistance phenotypes, current computational methods have limitations. Standard machine learning models treat the genome as an unordered collection of features, ignoring the sequential context of Single Nucleotide Polymorphisms (SNPs). State-of-the-art sequence models like Transformers are often too data-hungry and computationally expensive for the moderately-sized datasets that are typical in this domain. To address these challenges, we propose AMR-EnsembleNet, an ensemble framework that synergistically combines sequence-based and feature-based learning. We developed a lightweight, custom 1D Convolutional Neural Network (CNN) to efficiently learn predictive sequence motifs from high-dimensional SNP data. This sequence-aware model was ensembled with an XGBoost model, a powerful gradient boosting system adept at capturing complex, non-local feature interactions. We trained and evaluated our framework on a benchmark dataset of 809 E. coli strains, predicting resistance across four antibiotics with varying class imbalance. Our 1D CNN-XGBoost ensemble consistently achieved top-tier performance across all the antibiotics, reaching a Matthews Correlation Coefficient (MCC) of 0.926 for Ciprofloxacin (CIP) and the highest Macro F1-score of 0.691 for the challenging Gentamicin (GEN) AMR prediction. We also show that our model consistently focuses on SNPs within well-known AMR genes like fusA and parC, confirming it learns the correct genetic signals for resistance. Our work demonstrates that fusing a sequence-aware 1D CNN with a feature-based XGBoost model creates a powerful ensemble, overcoming the limitations of using either an order-agnostic or a standalone sequence model.
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