Noncoding RNA gene detection using comparative sequence analysis.

@article{citeulike:118802, 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.}, address = {Howard Hughes Medical Institute and Department of Genetics, Washington University School of Medicine, Saint Louis, Missouri, USA. elena@genetics.wustl.edu}, author = {Rivas, E. and Eddy, S. R. }, citeulike-article-id = {118802}, issn = {1471-2105}, journal = {BMC Bioinformatics}, keywords = {alignment, noncoding, prediction, rna, secondary\_structure}, number = {1}, posted-at = {2007-01-05 20:01:59}, priority = {4}, title = {Noncoding RNA gene detection using comparative sequence analysis.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/11801179}, volume = {2}, year = {2001} }

TY - JOUR ID - citeulike:118802 L3 - citeulike-article-id:118802 TI - Noncoding RNA gene detection using comparative sequence analysis. JF - BMC Bioinformatics VL - 2 IS - 1 AD - Howard Hughes Medical Institute and Department of Genetics, Washington University School of Medicine, Saint Louis, Missouri, USA. elena@genetics.wustl.edu SN - 1471-2105 N2 - 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. KW - alignment KW - noncoding KW - prediction KW - rna KW - secondary_structure AU - Rivas, E AU - Eddy, SR PY - 2001/// UR - http://view.ncbi.nlm.nih.gov/pubmed/11801179 ER -