Commit 98fec788 authored by Jerome Waldispuhl's avatar Jerome Waldispuhl
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parents 987c1266 621bb00d
......@@ -80,7 +80,7 @@ We identified four major misunderstandings that likely resulted in low appreciat
\claimstag There is a misunderstanding of the claims made in this manuscript. In particular, as stated on page~5, we do not advocate for an energy-based natural selection model (i.e. \maternal). Instead, we support the hypothesis that RNA were randomly replicated and that stable complex structures have been spontaneously discovered (See page~4).\\
\experimentstag Comparison and experiments with an uniform sampling model appears to have been (unintentionally) ignored (See Fig.~6).\\
\experimentstag Comparison and experiments with an uniform sampling model appears to have been (unintentionally) overlooked (See Fig.~6).\\
\hypothesistag The principles of the evolutionary scenario supported in this study have not been correctly interpreted.\\
......@@ -152,7 +152,7 @@ Another funny thing about the algorithm is the while loop. This means that no se
\begin{response}{
Section 4.2 - Should it be "where w is also a k-mutant of w0" not "where s' is also a k-mutant of w0"?}
Yet is has been fixed in the manuscript.
Yes, is has been fixed in the manuscript.
\end{response}
......@@ -171,7 +171,7 @@ Yes thanks for the observation it has been fixed in the manuscript.
\begin{response}{
In this work the authors explore the space of RNA sequences of length 50 through random sampling and through an evolutionary algorithm. They characterize some structural properties of the corresponding secondary structures paying attention in particular to the folding energy and to the GC content. This is a computationally intensive work that relies on efficient algorithms previously developed by the senior author of this work and other co-workers. While I do not have any technical objection to this study, I have found have major conceptual issues regarding the context and motivation of the study and the interpretation of the results.}
\methodstag There is a deep misunderstanding on how \rnamutants work. As discussed in Sec.4.2. it is not random but instead a weighted sampling of pairs sequence-stucture were the weight is the energy of the sequence folded in that particular structure, compared to energy of all other pairs sequence-structure such that the sequence is at distance $k$ from the wild type.
\rnamutantstag There is a deep misunderstanding on how \rnamutants works. As discussed in Sec.4.2. it is not random but instead a weighted sampling of pairs sequence-stucture where the weight is the energy of the sequence folded in that particular structure, compared to energy of all other pairs sequence-structure such that the sequence is at distance $k$ from the wild type.
\end{response}
\begin{response}{
......@@ -237,8 +237,8 @@ We agree with the suggested change and will update the sentence.
\begin{response}{
Page 11. Here there are some very general statements based on very few simulations: ... variation to overcome energy barriers and obtain energies reached by RNAmutants.? The population used was quite small in comparison to natural ones, and no effort to study other population sizes has been made. It is known that, despite the canalization of evolutionary dynamics, the ability to overcome energy barriers is strongly dependent on the product of the population size times the mutation rate. The barrier disappears when this product is large enough.
Last paragraph. It is stated that their algorithm fails to generate the structural complexity found in real populations?. Which real populations are the authors comparing with? A single one? The complete database? Is this comparison sensible at sufficiently long evolutionary times (natural versus synthetic populations)? Why should selection for stability be the only pressure determining the observed natural structures?}
\experimentstag We are confronted to technical limitations were length 50 is the upper limit for which we can conduct such an extensive search, which we compare with smaller size as seen in other papers~\cite{???}.
\claimstag We are comparing with the abundance of families with length around 50 which contain multiloops as shown in Fig.1. And we do not support the hypothesis that selection for stability is a good model since it does not correlate well with observations.
\experimentstag We are confronted with technical limitations were length 50 is the upper limit for which we can conduct such an extensive search, which we compare with smaller size as seen in other papers~\cite{???}.
\maternaltag We are comparing with the abundance of families with length around 50 which contain multiloops as shown in Fig.1. And we do not support the hypothesis that selection for stability is a good model since it does not correlate well with observations.
\end{response}
\begin{response}{
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