arXiv:2606.16477cs.CV2026-06

区分抗生素施加与实际起效,准确率达95.47%。

AURA: Active-Response Attribution under Treatment Ambiguity in Bacterial Cytological Profiling

  • 将问题转为能量约束的逆向归因,利用形态残差分解识别有效药物
  • 在跨实验批次数据上实现95.47%的精确匹配准确率
  • 无需菌株标签,适合真实临床环境中的抗菌药活性分析

当细菌样本暴露于多种抗生素时,并非所有药物都起作用:若细菌对该药耐药,则不会产生形态变化。因此,真正有意义的是哪些药物实际起效,而非施加了哪些药物。我们在大肠杆菌显微图像中发现,施加组合与实际活性组合显著脱钩——简单假设二者一致的正确率仅约37%。现有计算工具难以恢复有效药物集:前向扰动模型(如scGen、CPA、IMPA)用于从处理预测表型,反向推导性能急剧下降;判别性图像分类器则容易记忆菌株和批次特异性纹理,无法跨实验迁移。我们提出AURA,将任务重构为受约束的能量基逆向归因。其核心归纳偏置是:有效药物集必须是施加药物集的子集,该约束大幅缩小候选空间。AURA通过将残留形态分解为抗生素响应原子,选择重建能量最低的子集来推断有效药物,且测试时不需菌株标签。AURA-E引入证据感知拒答机制,在候选解释近似合理时拒绝预测。在大肠杆菌细胞学谱图数据集的跨批次迁移测试中,AURA实现了95.47%的精确匹配准确率。

原文摘要 · Abstract (English)

When a bacterial sample is exposed to several antibiotics, not every applied drug necessarily acts: if the organism is resistant to one of them, that drug leaves no morphological trace. The clinically meaningful quantity is therefore not which antibiotics were applied, but which ones were active. We show that these two are sharply decoupled in real E. coli microscopy - naively assuming the applied combination equals the active one is correct only about 37% of the time - yet existing computational tools are ill-suited to recovering the active set. Forward perturbation models such as scGen, CPA, and IMPA are designed to predict appearance from treatment, not the reverse, and inverting them degrades sharply; discriminative image classifiers tend to memorise strain- and batch-specific texture and fail to transfer across experimental replicates. We introduce AURA, which reframes the task as constrained, energy-based inverse attribution. Its central inductive bias is that the active set must be a subset of the applied set; this collapses the candidate space and lets AURA infer the active subset of applied antibiotics by decomposing residual morphology into antibiotic response atoms and selecting the subset with the lowest reconstruction energy, using no strain label at test time. AURA-E adds evidence-aware abstention, withholding a prediction when candidate explanations remain near-equally plausible. On cross-replicate transfer in an E. coli cytological profiling dataset, AURA recovers the active antibiotic combination with 95.47% exact-match accuracy.

抗生素图像分析逆向归因机器学习

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