RCARE: RNA Sequence Comparison and Annotation for RNA Editing

The post-transcriptional sequence modification of transcripts through RNA editing is an important mechanism for regulating protein function and is associated with human disease phenotypes. The identification of RNA editing or RNA-DNA difference (RDD) sites is a fundamental step in the study of RNA editing. However, a substantial number of false-positive RDD sites have been identified recently. A major challenge in identifying RDD sites is to distinguish between the true RNA editing sites and the false positives. Furthermore, determining the location of condition-specific RDD sites and elucidating their functional roles will help toward understanding various biological phenomena that are mediated by RNA editing. The present study developed RNA-sequence comparison and annotation for RNA editing (RCARE) for searching, annotating, and visualizing RDD sites using thousands of previously known editing sites, which can be used for comparative analyses between multiple samples. RCARE also provides evidence for improving the reliability of identified RDD sites. RCARE is a web-based comparison, annotation, and visualization tool, which provides rich biological annotations and useful summary plots. The developers of previous tools that identify or annotate RNA-editing sites seldom mention the reliability of their respective tools. In order to address the issue, RCARE utilizes a number of scientific publications and databases to find specific documentations respective to a particular RNA-editing site, which generates evidence levels to convey the reliability of RCARE. Sequence-based alignment files can be converted into VCF files using a Python script and uploaded to the RCARE server for further analysis. RCARE is available for free at http://www.snubi.org/software/rcare/.

[1]  Jin Billy Li,et al.  Comment on “Widespread RNA and DNA Sequence Differences in the Human Transcriptome” , 2012, Science.

[2]  Madhur Kumar,et al.  Nuclear antisense RNA induces extensive adenosine modifications and nuclear retention of target transcripts. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[3]  B. Williams,et al.  RNA editing in the human ENCODE RNA-seq data , 2012, Genome research.

[4]  K. Nishikura,et al.  Editor meets silencer: crosstalk between RNA editing and RNA interference , 2006, Nature Reviews Molecular Cell Biology.

[5]  Bjorn-Erik Wulff,et al.  Modulation of microRNA expression and function by ADARs. , 2012, Current topics in microbiology and immunology.

[6]  Jin Billy Li,et al.  RADAR: a rigorously annotated database of A-to-I RNA editing , 2013, Nucleic Acids Res..

[7]  Heng Li,et al.  Tabix: fast retrieval of sequence features from generic TAB-delimited files , 2011, Bioinform..

[8]  Gonçalo R. Abecasis,et al.  The variant call format and VCFtools , 2011, Bioinform..

[9]  Yukio Kawahara,et al.  A-to-I RNA Editing and Human Disease , 2006, RNA biology.

[10]  H. Hakonarson,et al.  ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data , 2010, Nucleic acids research.

[11]  J. E. Smith,et al.  A double-stranded RNA unwinding activity introduces structural alterations by means of adenosine to inosine conversions in mammalian cells and Xenopus eggs. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Jae-Hyung Lee,et al.  Accurate identification of A-to-I RNA editing in human by transcriptome sequencing. , 2012, Genome research.

[13]  Life Technologies,et al.  A map of human genome variation from population-scale sequencing , 2011 .

[14]  K. Nishikura,et al.  Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Steven L Salzberg,et al.  Fast gapped-read alignment with Bowtie 2 , 2012, Nature Methods.

[16]  Joseph K. Pickrell,et al.  Comment on “Widespread RNA and DNA Sequence Differences in the Human Transcriptome” , 2012, Science.

[17]  K. Nishikura Functions and regulation of RNA editing by ADAR deaminases. , 2010, Annual review of biochemistry.

[18]  D. Altshuler,et al.  A map of human genome variation from population-scale sequencing , 2010, Nature.

[19]  Ernesto Picardi,et al.  REDItools: high-throughput RNA editing detection made easy , 2013, Bioinform..

[20]  Pavel V. Baranov,et al.  DARNED: a DAtabase of RNa EDiting in humans , 2010, Bioinform..

[21]  Lior Pachter,et al.  Sequence Analysis , 2020, Definitions.

[22]  Alfredo Ferro,et al.  VIRGO: visualization of A-to-I RNA editing sites in genomic sequences , 2013, BMC Bioinformatics.

[23]  Gonçalo R. Abecasis,et al.  The Sequence Alignment/Map format and SAMtools , 2009, Bioinform..

[24]  Mattia D'Antonio,et al.  ExpEdit: a webserver to explore human RNA editing in RNA-Seq experiments , 2011, Bioinform..

[25]  Mingyao Li,et al.  Widespread RNA and DNA Sequence Differences in the Human Transcriptome , 2011, Science.