EpiPAMPAS: Rapid detection of intra-protein epistasis via parsimonious ancestral state reconstruction and counting mutations

An epistatic interaction is a non-linear combination of effects of individual mutations on fitness. This type of interaction is a known driver for evolution, as they alter the organism’s fitness and adaptability. In this work we introduce EpiPAMPAS, a statistical method that is based on multiple sequence alignments (MSA) and detecting mutations in the same direction on a dendrogram instead of a phylogenetic tree using the Sankoff algorithm.

Results

We tested EpiPAMPAS on both simulated and real sequencing data. On the simulated data, our method was able to detect the simulated epistatic pairs with very low p-value. In a real-world application, we tested the influenza proteins N1, N2, H1, H3 and HIV-1 envelope protein subtypes A, B and C. We observe that EpiPAMPAS detects fewer interacting pairs than comparable statistical approaches, although the overlap between detected positions is good. Moreover, some of the amino acids from the detected pairs are known to be deleterious for viral fitness.

Availability

EpiPAMPAS is available under MIT license at https://github.com/kalininalab/EpiPAMPAS