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

arXiv: https://arxiv.org/abs/2606.16477 · HTML: https://mlsanity.com/paper/2606.16477/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 12 of its 61 references that are in the map.
- First posted on arXiv 15 Jun 2026.

## Builds on (most cited first, 12 of 12)

- [Deep Residual Learning for Image Recognition](https://mlsanity.com/paper/1512.03385/) (2015)
- [An Image is Worth 16x16 Words: Transformers for Image Recognition at Scale](https://mlsanity.com/paper/2010.11929/) (2020)
- [DINOv2: Learning Robust Visual Features without Supervision](https://mlsanity.com/paper/2304.07193/) (2023)
- [Selective Classification for Deep Neural Networks](https://mlsanity.com/paper/1705.08500/) (2017)
- [Your Classifier is Secretly an Energy Based Model and You Should Treat it Like One](https://mlsanity.com/paper/1912.03263/) (2019)
- [Structured Prediction Energy Networks](https://mlsanity.com/paper/1511.06350/) (2015)
- [Masked Autoencoders for Microscopy are Scalable Learners of Cellular Biology](https://mlsanity.com/paper/2404.10242/) (2024)
- [RxRx1: A Dataset for Evaluating Experimental Batch Correction Methods](https://mlsanity.com/paper/2301.05768/) (2023)
- [End-to-End Learning for Structured Prediction Energy Networks](https://mlsanity.com/paper/1703.05667/) (2017)
- [Learning Discrete Energy-based Models via Auxiliary-variable Local Exploration](https://mlsanity.com/paper/2011.05363/) (2020)
- [RxRx3-core: Benchmarking drug-target interactions in High-Content Microscopy](https://mlsanity.com/paper/2503.20158/) (2025)
- [MorphGen: Controllable and Morphologically Plausible Generative Cell-Imaging](https://mlsanity.com/paper/2510.01298/) (2025)

## Abstract (arXiv)

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.
