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Please see below the comments of our two reviewers and address the question at the end of Reviewer 2's review. I will accept the paper once I receive the revised version.
Hilton et al. present phydms, a software platform for the analysis of deep mutational scanning data. I have previously reviewed this manuscript with only minor comments, and all comments have been effectively addressed for this PeerJ submission. I have no further comments and I am happy to recommend for publication.
The authors describe a software package that informs phylogenetic analyses with data gathered from deep mutational scanning experiments. The experimentally informed codon model (ExpCM) uses site-specific amino acid preferences from DMS experiments modify the likelihood function for estimating tree branch lengths. This approach provides trees with improved likelihood and AIC. A number of interesting parameters are also estimated from the data including the experimental selection stringency and sites of diversifying selection. Overall, I found the paper to be well written and the methods thoroughly explained. As DMS experiments become more widespread, phydms should be a useful tool for understanding protein phylogeny and evolution.
One specific comment: could the authors please clarify what the last column of Table 1 refers to? Is this the number of sequences in the alignment? If so, these alignments seem a little small?
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