An evolution-based high-fidelity method of epistasis measurement: Theory and application to influenza

Author summary Interactions between genomic sites create a fitness landscape. The knowledge of topology and strength of interactions is vital for predicting the escape of viruses from drugs and immune response and their passing through fitness valleys. Many efforts have been invested into measuring these interactions from DNA sequence sets. Unfortunately, reproducibility of the results remains low due partly to a very small fraction of interaction pairs and partly to stochastic linkage noise masking true interactions. Here we propose a method to separate stochastic linkage and indirect interactions from epistatic interactions and apply it to influenza virus sequence data.