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

The analysis presented in this Brief Communication shows that, despite their complexity, current deep learning models do not outperform linear baselines in predicting gene perturbation effects, thus emphasizing the importance of further method development and thorough evaluation.

Brief Communication Open access Published: 04 August 2025 Constantin Ahlmann-Eltze ORCID: orcid.org/0000-0002-3762-068X1,2 nAff3, Wolfgang Huber ORCID: orcid.org/0000-0002-0474-22182 & Simon Anders ORCID: orcid.org/0000-0003-4868-18051 Nature Methods volume 22, pages 1657–1661 (2025) Cite this article 118k Accesses 250 Citations 200 Altmetric Metrics details 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…

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