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preprint✓ VerifiedPreprint — not peer reviewedVC0167

Genetic Perturbation Prediction Models Fail Out-of-Distribution: A Rigorous Benchmark and Systematic Evaluation

Preprint (not peer-reviewed): Tiwari et al. (Elucidata Corporation) introduce EL-PERTURB (Extrapolative Learning for PERTURBation Prediction), a benchmark that tests 20 perturbation-prediction models from six architecture classes on essential-gene and genome-wide Perturb-seq screens, using a stratified out-of-distribution split that places train and test sets in functionally distinct regions of transcriptional space. The authors report that performance degrades substantially under OOD conditions and that architectural complexity, including single-cell foundation-model embeddings, gives no reliable advantage over well-tuned simpler baselines. Company-authored; no independent replication yet.

Authors / organisation
Tiwari K, Mahajan G, Bellad RP, Dhruw NK, Jha AK.
Venue
bioRxiv (preprint, not peer-reviewed)
Date
2026-10-19
Type
preprint
Year
2026
DOI
10.64898/2026.10.16.759604
Verification
bioRxiv API details (title, 5 authors, posted 2026-10-19, v1, new results, systems biology, CC BY, corresponding institution Elucidata Corporation, abstract) + Crossref posted-content record fetched 2026-10-21; full text not read; KB id VC0167 (renumbered 2026-10-20)

Benchmark & validationCritiquePerturbationPerturb-seqFoundation model

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