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Originally published in Science Express on 3 July 2008
Science 15 August 2008:
Vol. 321. no. 5891, pp. 956 - 960
DOI: 10.1126/science.1160342
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Reports

A Global View of Gene Activity and Alternative Splicing by Deep Sequencing of the Human Transcriptome

Marc Sultan,1* Marcel H. Schulz,2,3* Hugues Richard,2* Alon Magen,1 Andreas Klingenhoff,4 Matthias Scherf,4 Martin Seifert,4 Tatjana Borodina,1 Aleksey Soldatov,1 Dmitri Parkhomchuk,1 Dominic Schmidt,1 Sean O'Keeffe,2 Stefan Haas,2 Martin Vingron,2 Hans Lehrach,1 Marie-Laure Yaspo1{dagger}

The functional complexity of the human transcriptome is not yet fully elucidated. We report a high-throughput sequence of the human transcriptome from a human embryonic kidney and a B cell line. We used shotgun sequencing of transcripts to generate randomly distributed reads. Of these, 50% mapped to unique genomic locations, of which 80% corresponded to known exons. We found that 66% of the polyadenylated transcriptome mapped to known genes and 34% to nonannotated genomic regions. On the basis of known transcripts, RNA-Seq can detect 25% more genes than can microarrays. A global survey of messenger RNA splicing events identified 94,241 splice junctions (4096 of which were previously unidentified) and showed that exon skipping is the most prevalent form of alternative splicing.

1 Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, 14195 Berlin, Germany.
2 Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, 14195 Berlin, Germany.
3 International Max Planck Research School for Computational Biology and Scientific Computing.
4 Genomatix Software Gmbh, Bayerstrasse 85a, 80335 Munich, Germany.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: yaspo{at}molgen.mpg.de

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