# Learning Perturbation-Specific Representations through Conditional Energy Prior for Cellular Response Prediction

arXiv: https://arxiv.org/abs/2610.18456 · HTML: https://mlsanity.com/paper/2610.18456/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 6 of its 34 references that are in the map.
- First posted on arXiv 13 Oct 2026.

## Builds on (most cited first, 6 of 6)

- [How to Build the Virtual Cell with Artificial Intelligence: Priorities and Opportunities](https://mlsanity.com/paper/2409.11654/) (2024)
- [Model Agnostic Sample Reweighting for Out-of-Distribution Learning](https://mlsanity.com/paper/2301.09819/) (2023)
- [Modelling Cellular Perturbations with the Sparse Additive Mechanism Shift Variational Autoencoder](https://mlsanity.com/paper/2311.02794/) (2023)
- [Latent Space Energy-Based Model of Symbol-Vector Coupling for Text Generation and Classification](https://mlsanity.com/paper/2108.11556/) (2021)
- [PerturbDiff: Functional Diffusion for Single-Cell Perturbation Modeling](https://mlsanity.com/paper/2602.19685/) (2026)
- [What Makes a Representation Good for Single-Cell Perturbation Prediction?](https://mlsanity.com/paper/2605.19343/) (2026)

## Abstract (arXiv)

AI-based cellular perturbation prediction is essential to accelerate drug discovery and therapeutic identification. However, perturbation-specific signals are generally obscured by cellular complexity, making it difficult for existing methods to correctly capture perturbation effects. To address this problem, we propose PerturbEnergy, which introduces a conditional energy-based prior over perturbation representations. It assigns lower energy (higher probability) to representations compatible with the given perturbation and higher energy to others, thereby explicitly tilting the latent space toward perturbation-preferred regions. Besides, PerturbEnergy can be integrated into autoencoder architectures as we find its Evidence Lower Bound (ELBO) is equivalent to the ELBO of the complete autoencoder. We further prove that optimizing PerturbEnergy increases the lower bound on the conditional mutual information between representation and perturbation. Extensive experiments on four benchmark datasets demonstrate the effectiveness of our PerturbEnergy: it improves perturbation recognition especially in latent space with improvement of up to 83.2%; It also achieves state-of-the-art performance for predicting top-50/100/200 differentially expressed gene(DEG) response and remaining competitive on highly variable gene(HVG) prediction. The code is provided: https://github.com/BlueWhaleLab/PerturbEnergy