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

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  • Additional Information
    • Publisher Information:
      eScholarship, University of California 2015-06-16
    • Abstract:
      BackgroundThe 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.ResultsWe 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.ConclusionsThe 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.
    • Subject Terms:
      Fetal Heart; Brain; Hela Cells; Myocytes; Cardiac; Humans; Sodium-Calcium Exchanger; RNA; RNA Splice Sites; Small Nuclear; Models; Statistical; Genomics; Evolution; Molecular; Organ Specificity; RNA Splicing; Fetal Development; Algorithms; Circular; HeLa Cells; Genetics; 1.1 Normal biological development and functioning; Bioinformatics; Environmental Sciences; Biological Sciences; Information and Computing Sciences; article
    • Availability:
      Open access content. Open access content
      public
    • Note:
      application/pdf
      Genome biology vol 16, iss 1, 126 1474-7596
    • Other Numbers:
      CDLER oai:escholarship.org:ark:/13030/qt5894f1s2
      qt5894f1s2
      https://escholarship.org/uc/item/5894f1s2
      https://escholarship.org/
      1287297719
    • Contributing Source:
      UC MASS DIGITIZATION
      From OAIster®, provided by the OCLC Cooperative.
    • Accession Number:
      edsoai.on1287297719
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