Commit 53f34956 authored by Jerome Waldispuhl's avatar Jerome Waldispuhl
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Page 7. A fixed number of sequence-structure pairs is sampled at each mutational distance. How can we be sure that results do not depend on the relative size of the sample with respect to the total number of available sequences? Is it just a coincidence that the largest number of sequences occurs for a GC content of 50\% and at a distance of 35 mutations from any sequence (figure S7)? Though extremely intensive, the exploration performed here is very far from being exhaustive, so results could be easily biased (there are multiple examples of such deviations in the literature due to the vastness of the genotype space).}
\claimstag Estimating the number of samples required to have a representative set is always challenging, and there is to our knowledge ni. Nonetheless, we
\claimstag Estimating the number of samples required to generate a representative set is always challenging, and there is to our knowledge no universal method to estimate accurate lower bounds. Nonetheless, we obviously explored this question. In preliminary studies, we varied the sizes of neighbourhoods to guarantee reproducibility of our results. We will be happy to clarify it in a revised version of our manuscript.\\
Although, we are afraid that there is misunderstanding on the meaning of exhaustive explorations. Our dynamic programming programming algorithm calculates the contribution to the partition function of all pairs of sequence and structures possible \cite{Waldispuhl:2008aa}. In that sense, it is indeed exhaustive. The backtracking procedure uses the information stored in the dynamic tables to sample pairs of mutants and structures. The latter is obviously not exhaustive since it aims to extract most representative structures that will be used derive the frequencies of structural features.
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End of first paragraph in section 2.2 and later: This statement repeats a well-known effect in evolution: it has a much higher canalization of the search process, is much faster and, unavoidably, discards most alternatives when compared to random sampling.}
We agree with this comment. However, we do not understand the request. We could obviously add a reference if that is the purpose of this comment.
We agree with this comment, which is as noted by the reviewer already stated in our paper. However, we do not understand the request. We could obviously add a reference if that is the purpose of this comment.
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