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Detecting microRNA binding and siRNA off-target effects from expression data

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Abstract

Sylamer is a method for detecting microRNA target and small interfering RNA off-target signals in 3′ untranslated regions from a ranked gene list, sorted from upregulated to downregulated, after a microRNA perturbation or RNA interference experiment. The output is a landscape plot that tracks occurrence biases using hypergeometric P-values for all words across the gene ranking. We demonstrated the utility, speed and accuracy of this approach on several datasets.

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Figure 1: Mouse miR-155 knockout experiment.
Figure 2: Human RNAi off-target analysis.

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Acknowledgements

We thank R. Grocock, W. Khong, H. Saini, S. Manakov, J. van Helden, A. Giraldez and W. Huber for useful discussions. This work was supported by the Wellcome Trust.

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Author notes

  1. Stijn van Dongen & Anton J Enright

    Present address: Present address: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.,

  2. Stijn van Dongen and Cei Abreu-Goodger: These authors contributed equally to this work.

Authors and Affiliations

  1. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, Cambridge, UK

    Stijn van Dongen, Cei Abreu-Goodger & Anton J Enright

Authors
  1. Stijn van Dongen
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  2. Cei Abreu-Goodger
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  3. Anton J Enright
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Contributions

S.v.D., C.A.-G. and A.J.E. conceived and designed the method. S.v.D. implemented the method. C.A.-G. and S.v.D. perfomed the analyses and validation experiments. S.v.D., C.A.-G. and A.J.E. wrote the manuscript.

Corresponding author

Correspondence to Anton J Enright.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6, Supplementary Discussion, Supplementary Methods (PDF 7562 kb)

Supplementary Data 1

miR-155 genelists and sequences (ZIP 6555 kb)

Supplementary Data 2

miR-430 genelists and sequences (ZIP 1884 kb)

Supplementary Data 3

siRNA genelists and sequences (ZIP 8595 kb)

Supplementary Software

Sylamer source-code, binaries and JAVA interface (ZIP 9834 kb)

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van Dongen, S., Abreu-Goodger, C. & Enright, A. Detecting microRNA binding and siRNA off-target effects from expression data. Nat Methods 5, 1023–1025 (2008). https://doi.org/10.1038/nmeth.1267

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  • DOI: https://doi.org/10.1038/nmeth.1267

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