用生物信息指导表示学习,让质谱模型跨医院无须重训也能准确识别细菌。
Biologically Informed Representation Learning for Robust Cross-Center Generalization of MALDI-TOF Mass Spectrometry

- 融合设备差异与生物学信息,联合建模数据采集偏差和真实生物特征。
- 在7个跨国数据集上实现零样本微生物识别新纪录,抗药性预测也有效迁移。
- 适合临床机构部署,无需针对新医院重新训练,支持未知场景的可靠预测。
基于质谱的机器学习模型在微生物鉴定和耐药性预测等临床微生物学任务中展现出巨大潜力。然而,因设备差异导致的域偏移限制了其跨机构应用,现有模型常捕捉技术噪声而非可迁移的生物信息。本文提出DALMA,一种概率表示学习框架,同时建模采集差异与生物监督信号,学习具有生物结构的潜在表示。通过结合领域特定重建与生物引导表示学习,该方法在推理时无需机构特异性组件,实现对未见中心的零样本部署。我们在涵盖三个国家的七个数据集组成的多中心基准上评估,结果表明:在两个独立临床中心上,DALMA始终达到零样本微生物识别的最先进水平;且学习到的表示能有效迁移至耐药性预测任务。此外,潜在空间的新颖性估计可实现对未知域偏移下的可靠选择性预测。这些结果证明,生物信息引导的表示学习是实现临床微生物学中鲁棒、可迁移机器学习的有效策略。
原文摘要 · Abstract (English)
Machine learning models for MALDI-TOF mass spectrometry have shown considerable promise for clinical microbiology tasks such as microbial identification and antimicrobial resistance prediction. However, their deployment across institutions remains limited by domain shift, as acquisition-specific variability often leads models to capture technical artifacts rather than transferable biological information. Existing representation learning approaches primarily address this problem through statistical domain alignment while largely overlooking the biological supervision naturally available in microbiology datasets. We introduce DALMA, a probabilistic representation learning framework that jointly models acquisition-specific variability and biological supervision to learn biologically structured latent representations. By combining domain-specific reconstruction with biologically guided representation learning, DALMA learns transferable representations that generalize across heterogeneous clinical centers without requiring institution-specific components at inference, enabling zero-shot deployment on previously unseen sites. We evaluate DALMA on a multi-center benchmark comprising seven datasets from three countries. DALMA consistently achieves state-of-the-art zero-shot microbial identification across two held-out clinical centers, while the learned representations also transfer effectively to antimicrobial resistance prediction. Furthermore, latent-space novelty estimation enables reliable selective prediction under previously unseen domain shifts. These results demonstrate that biologically informed representation learning provides an effective strategy for robust and transferable ML in clinical microbiology.
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