Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing (original) (raw)

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

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

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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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  4. Brendan J Frey
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  5. Benjamin J Blencowe
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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 toBenjamin J Blencowe.

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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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