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Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development

BACKGROUND: The pervasive expression of circular RNA is a recently discovered feature of gene expression in highly diverged eukaryotes, but the functions of most circular RNAs are still unknown. Computational methods to discover and quantify circular RNA are essential. Moreover, discovering biologic...

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Autores principales: Szabo, Linda, Morey, Robert, Palpant, Nathan J., Wang, Peter L., Afari, Nastaran, Jiang, Chuan, Parast, Mana M., Murry, Charles E., Laurent, Louise C., Salzman, Julia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506483/
https://www.ncbi.nlm.nih.gov/pubmed/26076956
http://dx.doi.org/10.1186/s13059-015-0690-5
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author Szabo, Linda
Morey, Robert
Palpant, Nathan J.
Wang, Peter L.
Afari, Nastaran
Jiang, Chuan
Parast, Mana M.
Murry, Charles E.
Laurent, Louise C.
Salzman, Julia
author_facet Szabo, Linda
Morey, Robert
Palpant, Nathan J.
Wang, Peter L.
Afari, Nastaran
Jiang, Chuan
Parast, Mana M.
Murry, Charles E.
Laurent, Louise C.
Salzman, Julia
author_sort Szabo, Linda
collection PubMed
description BACKGROUND: The pervasive expression of circular RNA is a recently discovered feature of gene expression in highly diverged eukaryotes, but the functions of most circular RNAs are still unknown. Computational methods to discover and quantify circular RNA are essential. Moreover, discovering biological contexts where circular RNAs are regulated will shed light on potential functional roles they may play. RESULTS: We present a new algorithm that increases the sensitivity and specificity of circular RNA detection by discovering and quantifying circular and linear RNA splicing events at both annotated and un-annotated exon boundaries, including intergenic regions of the genome, with high statistical confidence. Unlike approaches that rely on read count and exon homology to determine confidence in prediction of circular RNA expression, our algorithm uses a statistical approach. Using our algorithm, we unveiled striking induction of general and tissue-specific circular RNAs, including in the heart and lung, during human fetal development. We discover regions of the human fetal brain, such as the frontal cortex, with marked enrichment for genes where circular RNA isoforms are dominant. CONCLUSIONS: The vast majority of circular RNA production occurs at major spliceosome splice sites; however, we find the first examples of developmentally induced circular RNAs processed by the minor spliceosome, and an enriched propensity of minor spliceosome donors to splice into circular RNA at un-annotated, rather than annotated, exons. Together, these results suggest a potentially significant role for circular RNA in human development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0690-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-45064832015-07-19 Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development Szabo, Linda Morey, Robert Palpant, Nathan J. Wang, Peter L. Afari, Nastaran Jiang, Chuan Parast, Mana M. Murry, Charles E. Laurent, Louise C. Salzman, Julia Genome Biol Research BACKGROUND: The pervasive expression of circular RNA is a recently discovered feature of gene expression in highly diverged eukaryotes, but the functions of most circular RNAs are still unknown. Computational methods to discover and quantify circular RNA are essential. Moreover, discovering biological contexts where circular RNAs are regulated will shed light on potential functional roles they may play. RESULTS: We present a new algorithm that increases the sensitivity and specificity of circular RNA detection by discovering and quantifying circular and linear RNA splicing events at both annotated and un-annotated exon boundaries, including intergenic regions of the genome, with high statistical confidence. Unlike approaches that rely on read count and exon homology to determine confidence in prediction of circular RNA expression, our algorithm uses a statistical approach. Using our algorithm, we unveiled striking induction of general and tissue-specific circular RNAs, including in the heart and lung, during human fetal development. We discover regions of the human fetal brain, such as the frontal cortex, with marked enrichment for genes where circular RNA isoforms are dominant. CONCLUSIONS: The vast majority of circular RNA production occurs at major spliceosome splice sites; however, we find the first examples of developmentally induced circular RNAs processed by the minor spliceosome, and an enriched propensity of minor spliceosome donors to splice into circular RNA at un-annotated, rather than annotated, exons. Together, these results suggest a potentially significant role for circular RNA in human development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0690-5) contains supplementary material, which is available to authorized users. BioMed Central 2015-06-16 2015 /pmc/articles/PMC4506483/ /pubmed/26076956 http://dx.doi.org/10.1186/s13059-015-0690-5 Text en © Szabo et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Szabo, Linda
Morey, Robert
Palpant, Nathan J.
Wang, Peter L.
Afari, Nastaran
Jiang, Chuan
Parast, Mana M.
Murry, Charles E.
Laurent, Louise C.
Salzman, Julia
Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development
title Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development
title_full Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development
title_fullStr Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development
title_full_unstemmed Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development
title_short Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development
title_sort statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular rna during human fetal development
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506483/
https://www.ncbi.nlm.nih.gov/pubmed/26076956
http://dx.doi.org/10.1186/s13059-015-0690-5
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