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An Unbiased Adaptive Sampling Algorithm for the Exploration of RNA Mutational Landscapes under Evolutionary Pressure

  • McGill University

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

Abstract

The analysis of the impact of mutations on folding properties of RNAs is essential to decipher principles driving molecular evolution and to design new molecules. We recently introduced an algorithm called RNAmutants which samples RNA sequence-structure maps in polynomial time and space. However, since the mutation probabilities depend of the free energy of the structures, RNAmutants is bias toward G+C-rich regions of the mutational landscape. In this paper we introduce an unbiased adaptive sampling algorithm that enables RNAmutants to sample regions of the mutational landscape poorly covered by previous techniques. We applied the method to sample mutations in complete RNA sequence-structures maps of sizes up to 40 nucleotides. Our results indicate that the G+C-contents has a strong influence on the evolutionary accessible structural ensembles. In particular, we show that low G+C-contents favor the apparition of internal loops, while high G+C-contents reduce the size of the evolutionary accessible mutational landscapes.

Original languageEnglish
Title of host publicationResearch in Computational Molecular Biology - 15th Annual International Conference, RECOMB 2011, Proceedings
EditorsVineet Bafna, S. Cenk Sahinalp
PublisherSpringer Verlag
Pages501-515
Number of pages15
ISBN (Print)9783642200359
DOIs
Publication statusPublished - 1 Jan 2011
Event15th Annual International Conference on Research in Computational Molecular Biology, RECOMB 2011 - Vancouver, Canada
Duration: 28 Mar 201131 Mar 2011

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume6577 LNBI
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349

Conference

Conference15th Annual International Conference on Research in Computational Molecular Biology, RECOMB 2011
Country/TerritoryCanada
CityVancouver
Period28/03/1131/03/11

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