CIRI: an efficient and unbiased algorithm for de novo circular RNA identification

Recent studies reveal that circular RNAs (circRNAs) are a novel class of abundant, stable and ubiquitous noncoding RNA molecules in animals. Comprehensive detection of circRNAs from high-throughput transcriptome data is an initial and crucial step to study their biogenesis and function. Here, we present a novel chiastic clipping signal-based algorithm, CIRI, to unbiasedly and accurately detect circRNAs from transcriptome data by employing multiple filtration strategies. By applying CIRI to ENCODE RNA-seq data, we for the first time identify and experimentally validate the prevalence of intronic/intergenic circRNAs as well as fragments specific to them in the human transcriptome.

[1]  H. Schellekens,et al.  The hepatitis delta (delta) virus possesses a circular RNA. , 1986, Nature.

[2]  Peter Goodfellow,et al.  Circular transcripts of the testis-determining gene Sry in adult mouse testis , 1993, Cell.

[3]  C. Cocquerelle,et al.  Mis‐splicing yields circular RNA molecules , 1993, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[4]  W. Filipowicz,et al.  Exonucleolytic processing of small nucleolar RNAs from pre-mRNA introns. , 1995, Genes & development.

[5]  S. Eddy.  Non–coding RNA genes and the modern RNA world , 2001, Nature Reviews Genetics.

[6]  Sanjay K. Singh,et al.  Two reactions of Haloferax volcanii RNA splicing enzymes: joining of exons and circularization of introns. , 2003, RNA.

[7]  J. Daròs,et al.  Viroids and viroid-host interactions. , 2005, Annual review of phytopathology.

[8]  Michael Q. Zhang,et al.  Characterization of RNase R-digested cellular RNA source that consists of lariat and circular RNAs from pre-mRNA splicing , 2006, Nucleic acids research.

[9]  William Stafford Noble,et al.  Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project , 2007, Nature.

[10]  T. Gingeras,et al.  Genome-wide transcription and the implications for genomic organization , 2007, Nature Reviews Genetics.

[11]  K. Karbstein,et al.  RNA takes center stage. , 2007, Biopolymers.

[12]  H. Nielsen,et al.  Group I introns: Moving in new directions , 2009, RNA biology.

[13]  Brad T. Sherman,et al.  Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists , 2008, Nucleic acids research.

[14]  Fangqing Zhao,et al.  inGAP: an integrated next-generation genome analysis pipeline , 2009, Bioinform..

[15]  William R. Jeck,et al.  Expression of Linear and Novel Circular Forms of an INK4/ARF-Associated Non-Coding RNA Correlates with Atherosclerosis Risk , 2010, PLoS genetics.

[16]  Samuel S. Shepard,et al.  Critical association of ncRNA with introns , 2010, Nucleic acids research.

[17]  Fangqing Zhao,et al.  inGAP-sv: a novel scheme to identify and visualize structural variation from paired end mapping data , 2011, Nucleic Acids Res..

[18]  Schraga Schwartz,et al.  Transcriptome-wide discovery of circular RNAs in Archaea , 2011, Nucleic acids research.

[19]  E. Lai,et al.  Discovery of hundreds of mirtrons in mouse and human small RNA data , 2012, Genome research.

[20]  Charles Gawad,et al.  Circular RNAs Are the Predominant Transcript Isoform from Hundreds of Human Genes in Diverse Cell Types , 2012, PloS one.

[21]  Julia Salzman,et al.  Cell-Type Specific Features of Circular RNA Expression , 2013, PLoS genetics.

[22]  J. Kjems,et al.  Natural RNA circles function as efficient microRNA sponges , 2013, Nature.

[23]  Sebastian D. Mackowiak,et al.  Circular RNAs are a large class of animal RNAs with regulatory potency , 2013, Nature.

[24]  Michael K. Slevin,et al.  Circular RNAs are abundant, conserved, and associated with ALU repeats. , 2013, RNA.

[25]  Heng Li.  Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM , 2013, 1303.3997.

[26]  Andrea Tanzer,et al.  A multi-split mapping algorithm for circular RNA, splicing, trans-splicing and fusion detection , 2014, Genome Biology.

[27]  Jing Wang,et al.  WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013 , 2013, Nucleic Acids Res..

[28]  Shanshan Zhu,et al.  Circular intronic long noncoding RNAs. , 2013, Molecular cell.

[29]  N. Sharpless,et al.  Detecting and characterizing circular RNAs , 2014, Nature Biotechnology.

[30]  P. Brown,et al.  Circular RNA Is Expressed across the Eukaryotic Tree of Life , 2014, PloS one.

[31]  D. Bartel,et al.  Expanded identification and characterization of mammalian circular RNAs , 2014, Genome Biology.