Calico's Multi-ISM cuts genomic saturation mutagenesis evaluations 45-fold
anshulkundaje · x · 2026-10-06
Calico Life Sciences researchers released a bioRxiv preprint introducing Multi-ISM, a scalable framework for saturation mutagenesis of long-context sequence-to-function models.
- Conventional in silico mutagenesis scores one mutation at a time, requiring millions of model evaluations per gene and billions to trillions at genome scale.
- Multi-ISM reformulates ISM as a sparse recovery problem, generating mutational maps with roughly 45-fold fewer model evaluations.
- The paper demonstrates scalable mapping of gene regulatory architecture and rare variant effects (authors include Han Yuan and David R Kelley).
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