Commit 0891e175 authored by Jerome Waldispuhl's avatar Jerome Waldispuhl
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add bib

parent 063575da
%% This BibTeX bibliography file was created using BibDesk.
%% http://bibdesk.sourceforge.net/
%% Created for Jerome Waldispuhl at 2017-08-13 18:13:07 -0400
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@article{Waldispuhl:2008aa,
Abstract = {The diversity and importance of the role played by RNAs in the regulation and development of the cell are now well-known and well-documented. This broad range of functions is achieved through specific structures that have been (presumably) optimized through evolution. State-of-the-art methods, such as McCaskill's algorithm, use a statistical mechanics framework based on the computation of the partition function over the canonical ensemble of all possible secondary structures on a given sequence. Although secondary structure predictions from thermodynamics-based algorithms are not as accurate as methods employing comparative genomics, the former methods are the only available tools to investigate novel RNAs, such as the many RNAs of unknown function recently reported by the ENCODE consortium. In this paper, we generalize the McCaskill partition function algorithm to sum over the grand canonical ensemble of all secondary structures of all mutants of the given sequence. Specifically, our new program, RNAmutants, simultaneously computes for each integer k the minimum free energy structure MFE(k) and the partition function Z(k) over all secondary structures of all k-point mutants, even allowing the user to specify certain positions required not to mutate and certain positions required to base-pair or remain unpaired. This technically important extension allows us to study the resilience of an RNA molecule to pointwise mutations. By computing the mutation profile of a sequence, a novel graphical representation of the mutational tendency of nucleotide positions, we analyze the deleterious nature of mutating specific nucleotide positions or groups of positions. We have successfully applied RNAmutants to investigate deleterious mutations (mutations that radically modify the secondary structure) in the Hepatitis C virus cis-acting replication element and to evaluate the evolutionary pressure applied on different regions of the HIV trans-activation response element. In particular, we show qualitative agreement between published Hepatitis C and HIV experimental mutagenesis studies and our analysis of deleterious mutations using RNAmutants. Our work also predicts other deleterious mutations, which could be verified experimentally. Finally, we provide evidence that the 3' UTR of the GB RNA virus C has been optimized to preserve evolutionarily conserved stem regions from a deleterious effect of pointwise mutations. We hope that there will be long-term potential applications of RNAmutants in de novo RNA design and drug design against RNA viruses. This work also suggests potential applications for large-scale exploration of the RNA sequence-structure network. Binary distributions are available at http://RNAmutants.csail.mit.edu/.},
Author = {Waldisp{\"u}hl, J{\'e}r{\^o}me and Devadas, Srinivas and Berger, Bonnie and Clote, Peter},
Date-Added = {2017-08-13 22:12:01 +0000},
Date-Modified = {2017-08-13 22:12:01 +0000},
Doi = {10.1371/journal.pcbi.1000124},
Journal = {PLoS Comput Biol},
Journal-Full = {PLoS computational biology},
Mesh = {Algorithms; Cluster Analysis; Computational Biology; Evolution, Molecular; HIV; Hepacivirus; Humans; Mutagenesis; Mutation; Nucleic Acid Conformation; RNA; Replicon; Response Elements; Software; Thermodynamics},
Month = {Aug},
Number = {8},
Pages = {e1000124},
Pmc = {PMC2475669},
Pmid = {18688270},
Pst = {epublish},
Title = {Efficient algorithms for probing the RNA mutation landscape},
Volume = {4},
Year = {2008},
Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pcbi.1000124}}
......@@ -40,7 +40,8 @@
\author{C. Oliver \and V. Reinharz \and J. Waldisp\"{u}hl}
\date{\today}
% Some of the article customizations are relevant for this class
% Customizations
\usepackage[super,comma,numbers]{natbib}
\usepackage{xcolor}
\usepackage{xspace}
\usepackage{tikz}
......@@ -84,7 +85,7 @@ We identified four major misunderstandings that likely resulted in low appreciat
\hypothesistag The principles of the evolutionary scenario supported in this study have not been correctly interpreted.\\
\methodstag The principles and output of \rnamutants \cite{???}, which has been used to characterized the energy landscape, are misundertood.\\
\methodstag The principles and output of \rnamutants \cite{Waldispuhl:2008aa}, which has been used to characterized the energy landscape, are misundertood.\\
We strongly believe that the misunderstandings cited above can be easily clarified in a revised version of the manuscript. Please, find below our detailed answers to the reviewers.
......@@ -155,7 +156,7 @@ The reviewer is correct. It is has been fixed in the manuscript.
\begin{response}{
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 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 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.
\end{response}
\begin{response}{
......@@ -254,5 +255,7 @@ Summarizing, I guess that the region of structural complexity (according to the
Voila
\end{response}
\bibliographystyle{unsrtnat}
\bibliography{appeal.bib}
\end{document}
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