Single-Cell Perturbation Modeling

Overview

Single-cell perturbation modeling asks how gene edits, drugs, and other interventions change cell states, including how responses differ across cells and conditions. Approaches include conditional flow-matching and diffusion models that generate response distributions, latent-variable models that separate perturbation effects from baseline cell state, and methods using regulatory networks, biological knowledge, or retrieval of similar experiments. Models are tested on settings such as Perturb-seq, drug-response atlases, and the Virtual Cell Challenge, with tasks including unseen perturbations, cell types, doses, and combinations. A central challenge is that strong benchmark scores may not transfer to new contexts or show that models learned target-specific mechanisms rather than shared background signals.

Latest papers

CardsList

61 papers9 papers in the last four weeks, up 13% on the four weeks before. 0.1% of all new papers.

  1. A Pitfall in the Evaluation of Gene Perturbation Models

    Oct 19, 2026George Panagopoulos, Saman Omidi, Tsz Pan Tong +1Single-Cell Perturbation ModelingDifferential Testing

  2. Synergy-Aware Residual Flow Matching for Single-Cell Perturbation Prediction

    Oct 18, 2026Jingrui Wu, Wangyun DanSingle-Cell Perturbation ModelingFlow-Based Generative Modeling

  3. CloneOT: predicting clone-specific perturbation responses with lineage-supervised neural inverse optimal transport

    Oct 12, 2026Yanshuo Chen, Wei Chen, Heng HuangSingle-Cell Perturbation ModelingInverse Optimal Transport

  4. TempoBridge: Source-Conditioned Flow Matching with Optimal Transport Couplings for Single-Cell Population Transitions

    Oct 4, 2026Bowen Han, Lingbei Meng, Shihuan Luo +7Single-Cell Perturbation ModelingConditional Flow Matching

  5. VCLMU: Mechanism-Centric Virtual Cell World Modeling for Perturbation Response

    Oct 3, 2026Yuwei Miao, Azim Dehghani Amirabad, Scott Oloff +3Single-Cell Perturbation ModelingWorld Model Learning

  6. DRIFT: Disentangled Responsive-Invariant Flow Transport for Single-Cell Perturbation Prediction

    Sep 28, 2026Mustapha Bounoua, Giulio Franzese, Pietro MichiardiDisentangled Representation LearningConditional Flow Matching

  7. P2P: Cross-View Population Denoising for Unpaired Single-Cell Perturbation Response Prediction

    Sep 28, 2026Haojie Yang, Ran SuSingle-Cell Perturbation ModelingSingle-Cell Transcriptomics

  8. Generalizable single-cell perturbation response prediction using energy-guided flow matching

    Sep 27, 2026Jianan Wei, Jiajun Hong, Guikun Chen +3Single-Cell Perturbation ModelingSingle-Cell Transcriptomics

  9. AmbiModBench: Benchmarking Gene Perturbation Prediction Beyond Shared Responses

    Sep 26, 2026Sikai Huang, Zhiwen Yang, Kai Yu +2Benchmark DesignSingle-Cell Perturbation Modeling

  10. Discover, Falsify, Revise: Auditing Input-Use Claims from Source Code to Predictive Contribution in Agent-Discovered Cell Models

    Sep 23, 2026Mengran Li, Bo Li, Chengyang Zhang +3AI Agents for Scientific DiscoveryAI Agent Auditing

  11. CellRFT: Reinforcement Fine-Tuning for Single-Cell Perturbation Modeling

    Sep 17, 2026Jie Yan, Li Liu, Hanze Guo +7Multi-Objective Reinforcement LearningSingle-Cell Perturbation Modeling

  12. An immune world model for multiscale forecasting and therapeutic hypothesis generation

    Sep 13, 2026Taoyong Cui, Xi Wang, Zonghang Li +11Action-Conditioned World ModelsSingle-Cell Perturbation Modeling

  13. PopPert: Population-level Joint-Distribution Modeling for Single-Cell Perturbation Prediction

    Sep 1, 2026Handong Wang, Jiaxin Qi, Haochen Feng +1Single-Cell Perturbation ModelingSingle-Cell RNA Sequencing

  14. DeMixPert: Decomposed Response Modeling with Gaussian Mixtures for OOD Single-Cell Perturbation Prediction

    Aug 24, 2026Jiawen Liu, Xuechenxiao Cao, Yutong Li +5Single-Cell Perturbation ModelingSingle-Cell Transcriptomics

  15. PerturbRx: Learning Treatment-Conditioned Latent Transitions for Patient Drug Response Prediction

    Aug 21, 2026Yoshitaka Inoue, Minoh Jeong, Alfred Hero +2Cancer Drug Response PredictionPredictive Representation Learning

  16. Joint Flow Matching Enables Continuous Dose-Conditioned Cell Morphing

    Aug 17, 2026Lea Bogensperger, Manuela Merlo, Martin Baumgartner +2Dose-Response EstimationSingle-Cell Perturbation Modeling

  17. Control-Anchored Residual Flow Matching Conditioned on Gene Geometry for Virtual Cell Perturbation Modeling

    Aug 7, 2026Quanquan Li, Yihe Chi, Liuyang Song +10Flow MatchingSingle-Cell Perturbation Modeling

  18. LLM-Guided Retrieval for Prediction of Molecular Perturbation Responses

    Aug 3, 2026Betty Xiong, Jan-Christian Huetter, Gabriele Scalia +2Single-Cell Perturbation ModelingDrug Discovery

  19. PerturbMap: Cross-Context Transfer of Single-Cell Perturbation Responses

    Jul 30, 2026Panpan Cui, Yiqi Liu, Wenhao SunSingle-Cell Perturbation ModelingCross-Domain Transfer Learning

  20. PerturbPFN: Probing the Limits of Synthetic Priors in Drug Perturbation Modelling

    Jul 26, 2026Yuche Gao, José Miguel Hernández-Lobato, Siyuan GuoSynthetic Data PretrainingStructural Causal Models

  21. PertReason: A Knowledge-Grounded Benchmark and Framework for Cell-State-Conditioned Mechanistic Reasoning of Perturbation Effects

    Jul 21, 2026Dongkwan Kim, Yiming Gao, Yining Yang +1LLM GroundingSingle-Cell Perturbation Modeling

  22. GeneSpeak-FP: Target and Compound Retrieval from Observed Cell-Level Perturbation Signatures

    Jul 20, 2026Kseniia Vaniushkina, Jeongmin Lim, Jinyong ParkSingle-Cell Perturbation ModelingInformation Retrieval

  23. Score Distributions, Not Cells: Evaluating Single-Cell Perturbations Under Class Overlap

    Jul 6, 2026Youssef Marrakchi, Davide D'Ascenzo, Sebastiano Cultrera di MontesanoSingle-Cell Perturbation ModelingClassification