Formal languages
Efficient string matching: an aid to bibliographic search
Communications of the ACM
INFO-RNA---a fast approach to inverse RNA folding
Bioinformatics
Inverting the Viterbi algorithm: an abstract framework for structure design
Proceedings of the 25th international conference on Machine learning
Bioinformatics
rnaDesign: local search for RNA secondary structure design
CIBCB'09 Proceedings of the 6th Annual IEEE conference on Computational Intelligence in Bioinformatics and Computational Biology
Controlled non-uniform random generation of decomposable structures
Theoretical Computer Science
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The problem of RNA secondary structure design is the following: given a target secondary structure, one aims to create a sequence that folds into, or is compatible with, a given structure. In several practical applications in biology, additional constraints must be taken into account, such as the presence/absence of regulatory motifs, either at a specific location or anywhere in the sequence. In this study, we investigate the design of RNA sequences from their targeted secondary structure, given these additional sequence constraints. To this purpose, we develop a general framework based on concepts of language theory, namely context-free grammars and finite state automata. We efficiently combine a comprehensive set of constraints into a unifying context-free grammar of moderate size. From there, we use generic algorithms to perform a (weighted) random generation, or an exhaustive enumeration, of candidate sequences. The resulting method, whose complexity scales linearly with the length of the RNA, was implemented as a standalone program. The resulting software was embedded into a publicly available dedicated web server. The applicability of the method was demonstrated on a concrete case study dedicated to Exon Splicing Enhancers, in which our approach was successfully used in the design of in vitro experiments.