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RNAsnp: Efficient Detection of Local RNA Secondary Structure Changes Induced by SNPs
Structural characteristics are essential for the functioning of many noncoding RNAs and cis-regulatory elements of mRNAs. SNPs may disrupt these structures, interfere with their molecular function, and hence cause a phenotypic effect. RNA folding algorithms can provide detailed insights into structu...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708107/ https://www.ncbi.nlm.nih.gov/pubmed/23315997 http://dx.doi.org/10.1002/humu.22273 |
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author | Sabarinathan, Radhakrishnan Tafer, Hakim Seemann, Stefan E Hofacker, Ivo L Stadler, Peter F Gorodkin, Jan |
author_facet | Sabarinathan, Radhakrishnan Tafer, Hakim Seemann, Stefan E Hofacker, Ivo L Stadler, Peter F Gorodkin, Jan |
author_sort | Sabarinathan, Radhakrishnan |
collection | PubMed |
description | Structural characteristics are essential for the functioning of many noncoding RNAs and cis-regulatory elements of mRNAs. SNPs may disrupt these structures, interfere with their molecular function, and hence cause a phenotypic effect. RNA folding algorithms can provide detailed insights into structural effects of SNPs. The global measures employed so far suffer from limited accuracy of folding programs on large RNAs and are computationally too demanding for genome-wide applications. Here, we present a strategy that focuses on the local regions of maximal structural change between mutant and wild-type. These local regions are approximated in a “screening mode” that is intended for genome-wide applications. Furthermore, localized regions are identified as those with maximal discrepancy. The mutation effects are quantified in terms of empirical P values. To this end, the RNAsnp software uses extensive precomputed tables of the distribution of SNP effects as function of length and GC content. RNAsnp thus achieves both a noise reduction and speed-up of several orders of magnitude over shuffling-based approaches. On a data set comprising 501 SNPs associated with human-inherited diseases, we predict 54 to have significant local structural effect in the untranslated region of mRNAs. RNAsnp is available at http://rth.dk/resources/rnasnp. |
format | Online Article Text |
id | pubmed-3708107 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-37081072013-07-12 RNAsnp: Efficient Detection of Local RNA Secondary Structure Changes Induced by SNPs Sabarinathan, Radhakrishnan Tafer, Hakim Seemann, Stefan E Hofacker, Ivo L Stadler, Peter F Gorodkin, Jan Hum Mutat Informatics Structural characteristics are essential for the functioning of many noncoding RNAs and cis-regulatory elements of mRNAs. SNPs may disrupt these structures, interfere with their molecular function, and hence cause a phenotypic effect. RNA folding algorithms can provide detailed insights into structural effects of SNPs. The global measures employed so far suffer from limited accuracy of folding programs on large RNAs and are computationally too demanding for genome-wide applications. Here, we present a strategy that focuses on the local regions of maximal structural change between mutant and wild-type. These local regions are approximated in a “screening mode” that is intended for genome-wide applications. Furthermore, localized regions are identified as those with maximal discrepancy. The mutation effects are quantified in terms of empirical P values. To this end, the RNAsnp software uses extensive precomputed tables of the distribution of SNP effects as function of length and GC content. RNAsnp thus achieves both a noise reduction and speed-up of several orders of magnitude over shuffling-based approaches. On a data set comprising 501 SNPs associated with human-inherited diseases, we predict 54 to have significant local structural effect in the untranslated region of mRNAs. RNAsnp is available at http://rth.dk/resources/rnasnp. Blackwell Publishing Ltd 2013-04 2013-01-11 /pmc/articles/PMC3708107/ /pubmed/23315997 http://dx.doi.org/10.1002/humu.22273 Text en Copyright © 2013 Wiley Periodicals, Inc., A Wiley Company http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. |
spellingShingle | Informatics Sabarinathan, Radhakrishnan Tafer, Hakim Seemann, Stefan E Hofacker, Ivo L Stadler, Peter F Gorodkin, Jan RNAsnp: Efficient Detection of Local RNA Secondary Structure Changes Induced by SNPs |
title | RNAsnp: Efficient Detection of Local RNA Secondary Structure Changes Induced by SNPs |
title_full | RNAsnp: Efficient Detection of Local RNA Secondary Structure Changes Induced by SNPs |
title_fullStr | RNAsnp: Efficient Detection of Local RNA Secondary Structure Changes Induced by SNPs |
title_full_unstemmed | RNAsnp: Efficient Detection of Local RNA Secondary Structure Changes Induced by SNPs |
title_short | RNAsnp: Efficient Detection of Local RNA Secondary Structure Changes Induced by SNPs |
title_sort | rnasnp: efficient detection of local rna secondary structure changes induced by snps |
topic | Informatics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708107/ https://www.ncbi.nlm.nih.gov/pubmed/23315997 http://dx.doi.org/10.1002/humu.22273 |
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