Importance of higher-order epistasis in large protein sequence-function relationships.

ABSTRACT: Epistasis complicates our understanding of protein sequence-function relationships and impedes our ability to build accurate predictive models for novel genotypes. Although pairwise epistasis has been extensively studied in proteins, the significance of higher-order epistasis for protein sequence-function relationships remains contentious, largely due to challenges in fitting higher-order epistatatic interactions for full-length proteins. Here, we introduce a novel transformer-based approach. The key feature of our method is that we can adjust the order of interactions fit by the model by changing the number of attention layers while also accounting for any global nonlinearity induced by the experimental conditions. This allows us to test if inclusion of higher-order interactions leads to

SUBMITTER: Sethi P 

PROVIDER: S-EPMC11463489 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature