A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome

Science. 2008 Aug 15;321(5891):956-60. doi: 10.1126/science.1160342. Epub 2008 Jul 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Cell Line
  • Cell Line, Tumor
  • Computational Biology
  • DNA, Complementary
  • DNA, Intergenic
  • Exons
  • Gene Expression Profiling*
  • Genome, Human*
  • Humans
  • Introns
  • Oligonucleotide Array Sequence Analysis
  • RNA Polymerase II / metabolism
  • RNA Splice Sites*
  • RNA, Messenger / genetics*
  • Sequence Analysis, RNA*


  • DNA, Complementary
  • DNA, Intergenic
  • RNA Splice Sites
  • RNA, Messenger
  • RNA Polymerase II

Associated data

  • GEO/GSE11892