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Deep-learning-based gene perturbation effect prediction does not yet outperform simple linear baselines

Constantin Ahlmann-Eltze, Wolfgang Huber, Simon Anders

2025Nature Methods92 citationsDOIOpen Access PDF

Abstract

Recent research in deep-learning-based foundation models promises to learn representations of single-cell data that enable prediction of the effects of genetic perturbations. Here we compared five foundation models and two other deep learning models against deliberately simple baselines for predicting transcriptome changes after single or double perturbations. None outperformed the baselines, which highlights the importance of critical benchmarking in directing and evaluating method development.

Topics & Concepts

Computer scienceComputational biologyMachine learningArtificial intelligenceSimple (philosophy)Perturbation (astronomy)Deep learningGeneBiologyGeneticsPhysicsPhilosophyEpistemologyQuantum mechanicsSingle-cell and spatial transcriptomicsGene Regulatory Network AnalysisGenomics and Chromatin Dynamics