VEFill: accurate and generalizable deep mutational scanning score imputation across protein domains (opens in new tab)

Deep Mutational Scanning (DMS) assays can systematically assess the effects of amino acid substitutions on protein function, but many datasets have incomplete variant coverage due to technical constraints. We developed VEFill (Variant Effect Fill), a gradient boosting model for imputing missing DMS scores across protein domains. Trained on the Human Domainome 1, VEFill integrates ESM-1v sequence embeddings, evolutionary conservation (EVE scores), amino acid substitution matrices, and physicoc...