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Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing

Nature Genetics volume 40, pages 1413–1415 (2008)Cite this article

An Addendum to this article was published on 01 June 2009

This article has been updated

Abstract

We carried out the first analysis of alternative splicing complexity in human tissues using mRNA-Seq data. New splice junctions were detected in ∼20% of multiexon genes, many of which are tissue specific. By combining mRNA-Seq and EST-cDNA sequence data, we estimate that transcripts from ∼95% of multiexon genes undergo alternative splicing and that there are ∼100,000 intermediate- to high-abundance alternative splicing events in major human tissues. From a comparison with quantitative alternative splicing microarray profiling data, we also show that mRNA-Seq data provide reliable measurements for exon inclusion levels.

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Figure 1: Assessing human alternative splicing complexity using mRNA-Seq data.
Figure 2: Assessing alternative splicing frequency using mRNA-Seq data.

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  • 28 April 2009

    Addendum: The GEO accession number for the mRNA-Seq datasets is GSE13652.

References

  1. Matlin, A.J., Clark, F. & Smith, C.W. Nat. Rev. Mol. Cell Biol. 6, 386–398 (2005).

    Article  CAS  Google Scholar 

  2. Blencowe, B.J. Cell 126, 37–47 (2006).

    Article  CAS  Google Scholar 

  3. Ben-Dov, C., Hartmann, B., Lundgren, J. & Valcarcel, J. J. Biol. Chem. 283, 1229–1233 (2008).

    Article  CAS  Google Scholar 

  4. Johnson, J.M. et al. Science 302, 2141–2144 (2003).

    Article  CAS  Google Scholar 

  5. Sorek, R., Dror, G. & Shamir, R. BMC Genomics 7, 273 (2006).

    Article  Google Scholar 

  6. Calarco, J.A. et al. Adv. Exp. Med. Biol. 623, 64–84 (2007).

    Article  Google Scholar 

  7. Bainbridge, M.N. et al. BMC Genomics 7, 246 (2006).

    Article  Google Scholar 

  8. Mortazavi, A., Williams, B.A., McCue, K., Schaeffer, L. & Wold, B. Nat. Methods 5, 621–628 (2008).

    Article  CAS  Google Scholar 

  9. Cloonan, N. et al. Nat. Methods 5, 613–619 (2008).

    Article  CAS  Google Scholar 

  10. Sultan, M. et al. Science 321, 956–960 (2008).

    Article  CAS  Google Scholar 

  11. Su, A.I. et al. Proc. Natl. Acad. Sci. USA 101, 6062–6067 (2004).

    Article  CAS  Google Scholar 

  12. Zhang, W. et al. J. Biol. 3, 21 (2004).

    Article  Google Scholar 

  13. Yeo, G., Holste, D., Kreiman, G. & Burge, C.B. Genome Biol. 5, R74 (2004).

    Article  Google Scholar 

  14. Schiaffino, S. & Reggiani, C. Physiol. Rev. 76, 371–423 (1996).

    Article  CAS  Google Scholar 

  15. Pan, Q. et al. Mol. Cell 16, 929–941 (2004).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank S. Luo, I. Khrebtukova and G. Schroth of Illumina Inc. for providing some of the mRNA-Seq datasets used in this analysis. We also thank M. Brudno, Y. Barash, J. Calarco and S. Ahmad for helpful suggestions and comments on the manuscript. B.J.B and B.J.F. acknowledge support from the Canadian Institutes of Health Research and from Genome Canada through the Ontario Genomics Institute.

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Authors and Affiliations

  1. Banting and Best Department of Medical Research, University of Toronto, Toronto, M5S 3E1, Canada

    Qun Pan, Ofer Shai, Leo J Lee, Brendan J Frey & Benjamin J Blencowe

  2. Department of Electrical and Computer Engineering, University of Toronto, Toronto, M5S 3G4, Canada

    Ofer Shai, Leo J Lee & Brendan J Frey

  3. Department of Molecular Genetics, University of Toronto, Toronto, M5S 3E1, Canada

    Benjamin J Blencowe

Authors
  1. Qun Pan
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  2. Ofer Shai
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  3. Leo J Lee
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Contributions

Q.P. created the exon and splice junction libraries and performed analyses of the mRNA-Seq, cDNA-EST and microarray data. O.S., L.J.L. and B.J.F. designed and implemented the logistic regression classifier and contributed to the analyses of tissue-specific alternative splicing events. The study was coordinated by B.J.B. The manuscript was prepared by B.J.B. and Q.P., with the participation of O.S., L.J.L. and B.J.F.

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Correspondence to Benjamin J Blencowe.

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Supplementary Methods, Supplementary Table 1 and Supplementary Figures 1 and 2 (PDF 329 kb)

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Pan, Q., Shai, O., Lee, L. et al. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet 40, 1413–1415 (2008). https://doi.org/10.1038/ng.259

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