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Many perturbation models are coming out!

Models developed for genetic/chemical perturbation data

Name Year Journal/Conf. Title
Rachel et al 2018 Pacific Symposium on Biocomputing 2018 Cell-specific prediction and application of drug-induced gene expression profiles
scGEN 2019 Nature Method scGen predicts single-cell perturbation responses
DTD 2019 The World Wide Web Conference, 2019 Modeling Relational Drug-Target-Disease Interactions via Tensor Factorization with Multiple Web Sources
CPA 2021 Molecular system biology Predicting cellular responses to complex perturbations in high‐throughput screens
CellBox 2021 Cell systems CellBox: Interpretable Machine Learning for Perturbation Biology with Application to the Design of Cancer Combination Therapy
CellDrift 2022 BIB CellDrift: inferring perturbation responses in temporally sampled single-cell data
MultiCPA 2022 MultiCPA: Multimodal Compositional Perturbation Autoencoder
PerturbNet 2022 PerturbNet predicts single-cell responses to unseen chemical and genetic perturbations
scINSIGHT 2022 Genome biology scINSIGHT for interpreting single-cell gene expression from biologically heterogeneous data
scpregan 2022 Bioinformatics scPreGAN, a deep generative model for predicting the response of single-cell expression to perturbation
Gears 2023 Nature Biotech Predicting transcriptional outcomes of novel multigene perturbations with GEARS
cycleCDR 2023 Interpretable Modeling of Single-cell perturbation Responses to Novel Drugs Using Cycle Consistence Learning
scVIDR 2023 Patterns Generative modeling of single-cell gene expression for dose-dependent chemical perturbations
Unagi 2023 Unagi: Deep Generative Model for Deciphering Cellular Dynamics and In-Silico Drug Discovery in Complex Diseases
CINEMA-OT 2023 Nature Method Causal identification of single-cell experimental perturbation effects with CINEMA-OT
ChemCPA 2023 NeurIPS 2022 Predicting Cellular Responses to Novel Drug Perturbations at a Single-Cell Resolution
DREEP 2023 BMC Medicine Predicting drug response from single-cell expression profiles of tumours
ontoVAE 2023 Bioinformatics Biologically informed variational autoencoders allow predictive modeling of genetic and drug-induced perturbations
scDiff 2023 A GENERAL SINGLE-CELL ANALYSIS FRAMEWORK VIA CONDITIONAL DIFFUSION GENERATIVE MODELS
ContrastiveVI 2023 Nature Method Isolating salient variations of interest in single-cell data with contrastiveVI
sVAE 2023 PMLR Learning Causal Representations of Single Cells via Sparse Mechanism Shift Modeling
CellOT 2023 Nature Method Learning single-cell perturbation responses using neural optimal transport
MOASL 2023 Computers in Biology and Medicine MOASL: Predicting drug mechanism of actions through similarity learning with transcriptomic signature
samsVAE 2024 Advances in Neural Information Processing Systems Modelling Cellular Perturbations with the Sparse Additive Mechanism Shift Variational Autoencoder
Biolord 2024 Nature Biotech Disentanglement of single-cell data with biolord
PDGrapher 2024 Nature Biomedical Engineering Combinatorial prediction of therapeutic perturbations using causally-inspired neural networks
TAT 2024 Journal of Chemical Information and Modeling Compound Activity Prediction with Dose-Dependent Transcriptomic Profiles and Deep Learning
scVAE 2024 A Supervised Contrastive Framework for Learning Disentangled Representations of Cell Perturbation Data
Cell PaintingCNN 2024 NC Learning representations for image-based profiling of perturbations
scDisInFact 2024 NC scDisInFact: disentangled learning for integration and prediction of multi-batch multi-condition single-cell RNA-sequencing data
CellCap 2024 Modeling interpretable correspondence between cell state and perturbation response with CellCap
CODEX 2024 Bioinformatics CODEX: COunterfactual Deep learning for the in silico EXploration of cancer cell line perturbations
scFM 2024 PertEval-scFM: Benchmarking Single-Cell Foundation Models for Perturbation Effect Prediction
STAMP 2024 NCS Toward subtask-decomposition-based learning and benchmarking for predicting genetic perturbation outcomes and beyond
PrePR-CT 2024 PrePR-CT: Predicting Perturbation Responses in Unseen Cell Types Using Cell-Type-Specific Graphs
PRnet 2024 NC Predicting transcriptional responses to novel chemical perturbations using deep generative model for drug discovery
TranSiGen 2024 NC Deep representation learning of chemical-induced transcriptional profile for phenotype-based drug discovery
BioDiscoveryAgent 2024 BioDiscoveryAgent: An AI Agent for Designing Genetic Perturbation Experiments
DRSPRING 2024 Computers in Biology and Medicine DRSPRING: Graph convolutional network (GCN)-Based drug synergy prediction utilizing drug-induced gene expression profile
PertKGE 2024 Identify compound-protein interaction with knowledge graph embedding of perturbation transcriptomics
scRank 2024 Cell Reports Medicine scRank infers drug-responsive cell types from untreated scRNA-seq data using a target-perturbed gene regulatory network
CellFlow 2025 CellFlow enables generative single-cell phenotype modeling with flow matching
TxPert 2025 TxPert: Leveraging Biochemical Relationships for Out-of-Distribution Transcriptomic Perturbation Prediction
IMPA 2025 NC Predicting cell morphological responses to perturbations using generative modeling
PS 2025 Nature Cell Biology Decoding heterogeneous single-cell perturbation responses
TRADE 2025 Nature Genetics Transcriptome-wide analysis of differential expression in perturbation atlases
UNAGI 2025 Nature Biomedical Engineering A deep generative model for deciphering cellular dynamics and in silico drug discovery in complex diseases
STATE 2025 Predicting cellular responses to perturbation across diverse contexts with State
scAgent 2025 scAgents:AMulti-AgentFramework forFullyAutonomousEnd-to-EndSingle-Cell PerturbationAnalysis
CONCERT 2025 CONCERT predicts niche-aware perturbation responses in spatial transcriptomics
Cradle-VAE 2025 AAAI Conference on AI Cradle-VAE: Enhancing Single-Cell Gene Perturbation Modeling with Counterfactual Reasoning-based Artifact Disentanglement
Pertpy 2025 NM Pertpy: an end-to-end framework for perturbation analysis
Scouter 2025 NCS Scouter predicts transcriptional responses to genetic perturbations with large language model embeddings
PertAdapt 2025 PertAdapt: Unlocking Single-Cell Foundation Models for Genetic Perturbation Prediction via Condition-Sensitive Adaptation
CausalGRN 2025 CausalGRN: deciphering causal gene regulatory networks from single-cell CRISPR screens
Systema 2025 Nature Biotechnology Systema: a framework for evaluating genetic perturbation response prediction beyond systematic variation
Stack 2026 Stack: In-Context Learning of Single-Cell Biology
AlphaCell 2026 Towards building a World Model to simulate perturbation-induced cellular dynamics by AlphaCell
XPert 2026 NMI Modelling drug-induced cellular perturbation responses with a biologically informed dual-branch transformer
PrePR-CT 2026 NMI Predicting and interpreting cell-type-specific drug responses in the small-data regime using inductive priors
SequenTx 2026 NMI Reinforcement learning-based design of sequential drug treatment targeting the evolving tumour landscape with SequenTx

Review

|2026|Nature Reviews Genetics| Interpretation, extrapolation and perturbation of single cells

Benchmark and Challenges

|2025|BMC genomics| Benchmarking foundation cell models for post-perturbation RNA-seq prediction
|2025| NM | Deep-learning-based gene perturbation effect prediction does not yet outperform simple linear baselines
|2025| Communications Biology | A large-scale benchmark for network inference from single-cell perturbation data
|2025| Bioinformatics | Simple controls exceed best deep learning algorithms and reveal foundation model effectiveness for predicting genetic perturbations

Perturbation Datasets

SC-perturb
C-MAP
PerturbBase
PerturDB
Tahoe-100M
Multiome Perturb-seq (paper)
Multiome: CRISPRmap (paper)
Spatial: Perturb-Fish (paper)
Spatial: PerturbView (paper)
Spatial: Perturb-map (paper)
Spatial: Perturb-DBiT (paper)
Spatial: Spatial-perturb-seq (paper)
Spatial: NIS-seq (paper)
Spatial: PERTURB-CAST (paper)

List of scFM

These tables will be periodically updated.

We will build APIs for some of these models on TDC for benchmarking.

Find single-cell data from CZI database

FastPert

A tool to quickly check:

Questions, ideas, comments, ...

Please contact Xiang Lin (xiang_lin@hms.harvard.edu).

Citation is appeciated

@misc{pertogether2025,
title = {PerTogether: A tool for perturbation research and modeling},
author = {Xiang Lin},
year = {2025},
url = {https://github.com/xianglin226/Benchmarking-Single-Cell-Perturbation/},
note = {Version 1.0}
}

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