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

@article{Pan2008DeepSO,
  title={Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing},
  author={Qun Pan and Ofer Shai and Leo J. Lee and Brendan J. Frey and Benjamin J. Blencowe},
  journal={Nature Genetics},
  year={2008},
  volume={40},
  pages={1413-1415}
}
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… 
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References

SHOWING 1-10 OF 22 REFERENCES
A Global View of Gene Activity and Alternative Splicing by Deep Sequencing of the Human Transcriptome
TLDR
A global survey of messenger RNA splicing events identified 94,241 splice junctions and showed that exon skipping is the most prevalent form of alternative splicing.
Genome-Wide Survey of Human Alternative Pre-mRNA Splicing with Exon Junction Microarrays
TLDR
These genome-wide data provide experimental evidence and tissue distributions for thousands of known and novel alternative splicing events and indicate that at least 74% of human multi-exon genes are alternatively spliced.
Genome-wide Analysis of Alternative Pre-mRNA Splicing*
TLDR
The picture emerging from these pioneering studies is that alternative splicing affects most human genes and a significant fraction of the genes in other multicellular organisms, with the potential to greatly influence the evolution of complex genomes.
Revealing global regulatory features of mammalian alternative splicing using a quantitative microarray platform.
TLDR
Interestingly, it is found that transcription and AS act independently on different sets of genes in order to define tissue-specific expression profiles, which reflect tissue identity.
Alternative Splicing: New Insights from Global Analyses
TLDR
Progress in establishing the full repertoire of functionally relevant transcript variants generated byAlternative splicing, the specific roles of such variants in normal and disease physiology, and how alternative splicing is coordinated on a global level to achieve cell- and tissue-specific functions are summarized in this review.
Variation in alternative splicing across human tissues
TLDR
This study distinguishes the human brain, testis and liver as having unusually high levels of AS, highlights differences in the types of AS occurring commonly in different tissues, and identifies candidate cis-regulatory elements and trans-acting factors likely to have important roles in tissue-specific AS in human cells.
Inferring global levels of alternative splicing isoforms using a generative model of microarray data
TLDR
An algorithm referred to as the Generative model for the Alternative Splicing Array Platform (GenASAP) is presented that can predict the levels of AS for thousands of exon skipping events using data generated from custom microarrays.
Understanding alternative splicing: towards a cellular code
TLDR
Traditional gene-by-gene investigations of alternative splicing mechanisms are now being complemented by global approaches that promise to reveal details of the nature and operation of cellular codes that are constituted by combinations of regulatory elements in pre-mRNA substrates and by cellular complements of splicing regulators, which together determine regulated splicing pathways.
Mapping and quantifying mammalian transcriptomes by RNA-Seq
TLDR
Although >90% of uniquely mapped reads fell within known exons, the remaining data suggest new and revised gene models, including changed or additional promoters, exons and 3′ untranscribed regions, as well as new candidate microRNA precursors.
Stem cell transcriptome profiling via massive-scale mRNA sequencing
TLDR
A massive-scale RNA sequencing protocol, short quantitative random RNA libraries or SQRL, is developed, highlighting how SQRL can be used to characterize transcriptome content and dynamics in a quantitative and reproducible manner, and suggesting that the understanding of transcriptional complexity is far from complete.
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