Fig. 1: Summary of analytical approach.
From: Parallel evolution in the emergence of highly pathogenic avian influenza A viruses
A summary of our approach to identifying HAPMs (HP-cluster associated parallel mutations) in AIV genomes. 1. Large-scale data curation and phylogenetic analysis to detect genotypes and phenotypes (HP lineages highlighted in red). 2. Phylogenetically informed subsampling to reduce alignment sizes, whilst retaining HP clusters and key mutational pathways along internal branches. 3. Detecting candidate HAPMs across multiple HP clusters (highlighted in orange) through the reconstruction of ancestral states. 4. Selecting HAPMs by statistical testing for genotype-to-phenotype associations using an evolutionary-informed model (represented in the matrix by aa Y occurring in Site X). 5. Identifying HAPMs evolving under positive selection using different dN/dS (ω) estimation methods. 6. Inferring the possible effects of HAPMs on protein structure stability and function, using existing structural data and experimental literature.
