Shared information between residues is sufficient to detect pair-wise epistasis in a protein

TL;DR

This paper discusses whether shared information between residues in a protein is sufficient to detect pair-wise epistasis, addressing a challenge to the idea that shared entropy implies epistatic interactions.

Contribution

The authors clarify that shared entropy between residues can indicate epistasis, countering previous skepticism and providing insights into detecting epistatic interactions in proteins.

Findings

Shared entropy can indicate epistasis between residues

Shared entropy does not necessarily imply direct epistasis

The paper clarifies the relationship between information sharing and epistasis

Abstract

In a comment on our manuscript "Strong selection significantly increases epistatic interactions in the long-term evolution of a protein", Dr. Crona challenges our assertion that shared entropy (that is, information) between two residues implies epistasis between those residues, by constructing an explicit example of three loci (say A, B, and C), where A and B are epistatically linked (leading to shared entropy between A and B), and A and C also depend epistatically (leading to shared entropy between A and C), so that loci B and C are correlated (share entropy).