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Specific alignment of structured RNA: stochastic grammars and sequence annealing

Bradley, Robert K. and Pachter, Lior and Holmes, Ian (2008) Specific alignment of structured RNA: stochastic grammars and sequence annealing. Bioinformatics, 24 (23). pp. 2677-2683. ISSN 1367-4803. PMCID PMC2732270. doi:10.1093/bioinformatics/btn495.

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Motivation: Whole-genome screens suggest that eukaryotic genomes are dense with non-coding RNAs (ncRNAs). We introduce a novel approach to RNA multiple alignment which couples a generative probabilistic model of sequence and structure with an efficient sequence annealing approach for exploring the space of multiple alignments. This leads to a new software program, Stemloc-AMA, that is both accurate and specific in the alignment of multiple related RNA sequences. Results: When tested on the benchmark datasets BRalibase II and BRalibase 2.1, Stemloc-AMA has comparable sensitivity to and better specificity than the best competing methods. We use a large-scale random sequence experiment to show that while most alignment programs maximize sensitivity at the expense of specificity, even to the point of giving complete alignments of non-homologous sequences, Stemloc-AMA aligns only sequences with detectable homology and leaves unrelated sequences largely unaligned. Such accurate and specific alignments are crucial for comparative-genomics analysis, from inferring phylogeny to estimating substitution rates across different lineages. Availability: Stemloc-AMA is available from as part of the dart software package for sequence analysis.

Item Type:Article
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URLURL TypeDescription CentralArticle
Pachter, Lior0000-0002-9164-6231
Additional Information:© The Author 2008. Published by Oxford University Press. Received on June 20, 2008; revised and accepted on September 15, 2008. Advance Access publication September 16, 2008. We thank Lars Barquist for computer support and Ariel Schwartz for the original development and implementation of the sequence annealing technique. Funding: NIH/NHGRI (grant 1R01GM076705); NSF CAREER award (CCF 03-47992 to L.P.); NSF Graduate Research Fellowship (to R.K.B.). Conflict of Interest: none declared.
Funding AgencyGrant Number
NSF Graduate Research FellowshipUNSPECIFIED
Issue or Number:23
PubMed Central ID:PMC2732270
Record Number:CaltechAUTHORS:20170307-103825678
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Official Citation:Robert K. Bradley, Lior Pachter, Ian Holmes; Specific alignment of structured RNA: stochastic grammars and sequence annealing. Bioinformatics 2008; 24 (23): 2677-2683. doi: 10.1093/bioinformatics/btn495
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74844
Deposited By: George Porter
Deposited On:07 Mar 2017 18:52
Last Modified:11 Nov 2021 05:30

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