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Identifying RNA editing sites using RNA sequencing data alone

Nature Methods volume 10, pages 128132 (2013) | Download Citation

Abstract

We show that RNA editing sites can be called with high confidence using RNA sequencing data from multiple samples across either individuals or species, without the need for matched genomic DNA sequence. We identified many previously unidentified editing sites in both humans and Drosophila; our results nearly double the known number of human protein recoding events. We also found that human genes harboring conserved editing sites within Alu repeats are enriched for neuronal functions.

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Acknowledgements

We thank E. Levanon, A. Fire and members of the Li lab for constructive discussions, S. Blair for assistance with data set curation, and modENCODE Consortium for the use of Drosophila RNA-seq data sets. G.R. and P.D. were supported by the Stanford Genome Training Program funded by the US National Institutes of Health. R.Z. was partially supported by a Dean's fellowship from Stanford University School of Medicine. R.P. was supported by a fellowship from the German Academic Exchange Service. This work was supported by startup funds from Stanford University Department of Genetics and Ellison Medical Foundation (to J.B.L.) and Medical Research Council, UK (to M.A.O.).

Author information

Author notes

    • Gokul Ramaswami
    •  & Rui Zhang

    These authors contributed equally to this work.

Affiliations

  1. Department of Genetics, Stanford University, Stanford, California, USA.

    • Gokul Ramaswami
    • , Rui Zhang
    • , Robert Piskol
    • , Patricia Deng
    •  & Jin Billy Li
  2. Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.

    • Liam P Keegan
    •  & Mary A O'Connell

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Contributions

G.R. and R.Z. performed computational analyses with help from R.P., P.D. and J.B.L.; R.Z. and G.R. carried out the validation experiments; L.P.K. and M.A.O. generated RNA-seq data for wild-type and Adar5G1 flies; and G.R., R.Z. and J.B.L. wrote the paper with input from other authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Jin Billy Li.

Supplementary information

PDF files

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    Supplementary Text and Figures

    Supplementary Figures 1–19, Supplementary Tables 1–10, Supplementary Notes 1–5

Excel files

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    Supplementary Data 1

    A-to-G mismatches identified in lymphoblastoid cell lines

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    Supplementary Data 2

    Non-A-to-G mismatches identified in lymphoblastoid cell lines

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    Supplementary Data 3

    A-to-G mismatches identified in human brain tissues

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    Supplementary Data 4

    Non-A-to-G mismatches identified in human brain tissues

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    Supplementary Data 5

    A-to-G mismatches identified in other human tissues

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    Supplementary Data 6

    Non-A-to-G mismatches identified in other human tissues

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    Supplementary Data 7

    A-to-G mismatches identified in primate cross-species comparison

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    Supplementary Data 8

    Non-A-to-G mismatches identified in primate cross-species comparison

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    Supplementary Data 9

    A-to-G mismatches identified in Drosophila cross-species comparison

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    Supplementary Data 10

    Non-A-to-G mismatches identified in Drosophila cross-species comparison

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DOI

https://doi.org/10.1038/nmeth.2330

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