## Analysis list#

This is not a complete list, but the new analyses will be described here. Other places to look are manuscript associated analyses, and the GitHub boards

### Contrast-FEL#

For each site in a codon alignment, estimate whether or not dN/dS ratios differ between sets of branches defined a priori. If the branches are associated with different selective environments, this could be used to generate a list of sites that may be evolving at different rates (under different selective pressures) in these environments.

• Outputs a list of sites where test branches have a statistically detectable difference in dN/dS from reference branches.
• Could be used to test for differential selection pressures, for example between host and recipient or individual anatomical compartments in HIV-1, or in between species with different phenotypes/traits.

Further information

### FitMultiModel#

For each alignment, FitMulti model fits five models, all extenstions of the Muse and Gaut (1994) codon model allowing for multiple instantaneous nucleotide changes within a codon to occur. Then pairwise likelihood ratio tests are performed between the models. This requires a codon alignment and a tree.

• Output includes the rate estimates for each model, the LRT p values, and a list of sites that show strong preference for multiple hit models.
• Can be used to determine the extent of multiple hits present in a data set.

Further information

### PRIME#

PRoperty Informed Models of Evolution Protein evolution models are typically based on estimates of amino acid exchangeabilities, e.g. as quantified in the BloSum substitution matrices which are still commonly used today. These models derive their power from the fact that radical substitutions – involving amino acids with very different physico-chemical properties – are generally rare, while conservative substitutions – involving similar amino acids – are more common. However, more recent studies have shown that amino acid exchangeabilities vary across organisms and across genes, reflecting the fact that the set of relevant physico-chemical properties changes from case to case, so that the same substitution may sometimes be radical (having a large effect on protein structure and/or function) and sometimes conservative (having little effect on structure or function). This variation can be expected from site to site within a protein: for instance, amino acids with different hydrophobicity may be unexchangeable at sites where the protein fold is sensitive to hydrophobicity but exchangeable at sites where it is not. PRIME models were designed to take account of this variation.

PRIME builds on the same conceptual frameworks as FEL[1] and MEME[2], but allows the non-synonymous substitution rate β depend not only on the site in question (like FEL and MEME), but also on which residues are being exchanged (e.g. I-V would be different from K-R).

Further information