Commit 676091fc authored by Jerome Waldispuhl's avatar Jerome Waldispuhl
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comments to ref 1

parent 0891e175
......@@ -156,7 +156,7 @@ The reviewer is correct. It is has been fixed in the manuscript.
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Section 4.2 A few lines down - "the structure sampled is not in general the MFE". I have not understood what the structure is when it is not the MFE structure of the sequence. How are the suboptimal structures of the sequence determined? The same question applies for the definition of Z on p19. In the sum for Z, are there many structures s' for each w'? What set of structures is allowed?}
\methodstag We believe that the For each sequence all possible non-pseudo-knotted structures are admissible (i.e. all structures deemed valid in \rnafold). The suboptimal sequence is not determined afterward. The sampling considers every possible pair sequence structure. It comes to the root of the \rnamutants algorithm [CITE]. Sampling MFE structures would require an exhaustive enumeration of all pair of sequences and MFE structures.
\methodstag It comes to the root of the \rnamutants algorithm \cite{Waldispuhl:2008aa}, which generalizes the \texttt{mfold} algorithm \cite{Zuker:1981aa} to mutant searches. Using dynamic programming techniques, mutants are mapped to all valid nested secondary structures (i.e. without pseudo-knot). Then, using a similar backtracking procedure as the one introduced in \texttt{Sfold} \cite{Ding:1999aa}, we sample pairs of mutant sequences and structures $(s,S)$ with a probability determined by the folding energy of $S$ on $s$. Sampling only MFE structures would require to guarantee their optimality, and require an exhaustive enumeration of all pair of sequences and MFE structures that breaks the dynamic programming scheme. Brute-force approaches are impossible to conduct on sequences of size 50, which is why previous exhaustive studies were limited to small sequences.
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