A continuous epistasis model for predicting growth rate given combinatorial variation in gene expression and environment.

ABSTRACT: Quantifying and predicting growth rate phenotype given variation in gene expression and environment is complicated by epistatic interactions and the vast combinatorial space of possible perturbations. We developed an approach for mapping expression-growth rate landscapes that integrates sparsely sampled experimental measurements with an interpretable machine learning model. We used mismatch CRISPRi across pairs and triples of genes to create over 8,000 titrated changes in E. coli gene expression under varied environmental contexts, exploring epistasis in up to 22 distinct environments. Our results show that a pairwise model previously used to describe drug interactions well-described these data. The model yielded interpretable parameters related to pathway architecture and generalized to p

SUBMITTER: Otto RM 

PROVIDER: S-EPMC10885703 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature