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Noncoding RNA gene detection using comparative sequence analysis.

E Rivas·S R Eddy
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Abstract

BACKGROUND: Noncoding RNA genes produce transcripts that exert their function without ever producing proteins. Noncoding RNA gene sequences do not have strong statistical signals, unlike protein coding genes. A reliable general purpose computational genefinder for noncoding RNA genes has been elusive. RESULTS: We describe a comparative sequence analysis algorithm for detecting novel structural RNA genes. The key idea is to test the pattern of substitutions observed in a pairwise alignment of two homologous sequences. A conserved coding region tends to show a pattern of synonymous substitutions, whereas a conserved structural RNA tends to show a pattern of compensatory mutations consistent with some base-paired secondary structure. We formalize this intuition using three probabilistic "pair-grammars": a pair stochastic context free grammar modeling alignments constrained by structural RNA evolution, a pair hidden Markov model modeling alignments constrained by coding sequence evolution, and a pair hidden Markov model modeling a null hypothesis of position-independent evolution. Given an input pairwise sequence alignment (e.g. from a BLASTN comparison of two related genomes) we classify the alignment into the coding, RNA, or null class according to the posterior probability of each class. CONCLUSIONS: We have implemented this approach as a program, QRNA, which we consider to be a prototype structural noncoding RNA genefinder. Tests suggest that this approach detects noncoding RNA genes with a fair degree of reliability.

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AlgorithmsAnimalsBase SequenceBayes TheoremCaenorhabditisCaenorhabditis elegansComputational BiologyComputer SimulationEscherichia coliGenomeGenome, BacterialModels, GeneticMolecular Sequence DataRNA, BacterialRNA, HelminthRNA, UntranslatedSalmonella typhiSensitivity and SpecificitySequence Analysis, RNAComparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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E Rivas, S R Eddy. 2001-10-10. Noncoding RNA gene detection using comparative sequence analysis.. https://doi.org/10.1186/1471-2105-2-8

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