Distinguishing direct interactions from global epistasis using rank statistics.

ABSTRACT: The phenotypic effect of a mutation may depend on the genetic background in which it occurs, a phenomenon referred to as epistasis. One source of epistasis in proteins is direct interactions between residues in close physical proximity to one another. However, epistasis may also occur in the absence of specific interactions between amino acids if the genotype-to-phenotype map is nonlinear. Disentangling the contributions of these two phenomena-specific and global epistasis-from noisy, high-throughput mutagenesis experiments is highly nontrivial: The form of the nonlinearity is generally not known and model misspecification may lead to over- or underestimation of specific epistasis. In contrast to previous approaches, we do not attempt to model the fitness measurements directly. Rather, we

SUBMITTER: Carlson MO 

PROVIDER: S-EPMC12501145 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature