Entropy measures quantify global splicing disorders in cancer.
Most mammalian genes are able to express several splice variants in a phenomenon known as alternative splicing. Serious alterations of alternative splicing occur in cancer tissues, leading to expression of multiple aberrant splice forms. Most studies of alternative splicing defects have focused on t...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2008-03-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18369415/?tool=EBI |
| _version_ | 1819036691108724736 |
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| author | William Ritchie Samuel Granjeaud Denis Puthier Daniel Gautheret |
| author_facet | William Ritchie Samuel Granjeaud Denis Puthier Daniel Gautheret |
| author_sort | William Ritchie |
| collection | DOAJ |
| description | Most mammalian genes are able to express several splice variants in a phenomenon known as alternative splicing. Serious alterations of alternative splicing occur in cancer tissues, leading to expression of multiple aberrant splice forms. Most studies of alternative splicing defects have focused on the identification of cancer-specific splice variants as potential therapeutic targets. Here, we examine instead the bulk of non-specific transcript isoforms and analyze their level of disorder using a measure of uncertainty called Shannon's entropy. We compare isoform expression entropy in normal and cancer tissues from the same anatomical site for different classes of transcript variations: alternative splicing, polyadenylation, and transcription initiation. Whereas alternative initiation and polyadenylation show no significant gain or loss of entropy between normal and cancer tissues, alternative splicing shows highly significant entropy gains for 13 of the 27 cancers studied. This entropy gain is characterized by a flattening in the expression profile of normal isoforms and is correlated to the level of estimated cellular proliferation in the cancer tissue. Interestingly, the genes that present the highest entropy gain are enriched in splicing factors. We provide here the first quantitative estimate of splicing disruption in cancer. The expression of normal splice variants is widely and significantly disrupted in at least half of the cancers studied. We postulate that such splicing disorders may develop in part from splicing alteration in key splice factors, which in turn significantly impact multiple target genes. |
| first_indexed | 2024-12-21T08:09:32Z |
| format | Article |
| id | doaj.art-d886706782b84fa8b4c3d3b123862386 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-21T08:09:32Z |
| publishDate | 2008-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-d886706782b84fa8b4c3d3b1238623862022-12-21T19:10:42ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582008-03-0143e100001110.1371/journal.pcbi.1000011Entropy measures quantify global splicing disorders in cancer.William RitchieSamuel GranjeaudDenis PuthierDaniel GautheretMost mammalian genes are able to express several splice variants in a phenomenon known as alternative splicing. Serious alterations of alternative splicing occur in cancer tissues, leading to expression of multiple aberrant splice forms. Most studies of alternative splicing defects have focused on the identification of cancer-specific splice variants as potential therapeutic targets. Here, we examine instead the bulk of non-specific transcript isoforms and analyze their level of disorder using a measure of uncertainty called Shannon's entropy. We compare isoform expression entropy in normal and cancer tissues from the same anatomical site for different classes of transcript variations: alternative splicing, polyadenylation, and transcription initiation. Whereas alternative initiation and polyadenylation show no significant gain or loss of entropy between normal and cancer tissues, alternative splicing shows highly significant entropy gains for 13 of the 27 cancers studied. This entropy gain is characterized by a flattening in the expression profile of normal isoforms and is correlated to the level of estimated cellular proliferation in the cancer tissue. Interestingly, the genes that present the highest entropy gain are enriched in splicing factors. We provide here the first quantitative estimate of splicing disruption in cancer. The expression of normal splice variants is widely and significantly disrupted in at least half of the cancers studied. We postulate that such splicing disorders may develop in part from splicing alteration in key splice factors, which in turn significantly impact multiple target genes.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18369415/?tool=EBI |
| spellingShingle | William Ritchie Samuel Granjeaud Denis Puthier Daniel Gautheret Entropy measures quantify global splicing disorders in cancer. PLoS Computational Biology |
| title | Entropy measures quantify global splicing disorders in cancer. |
| title_full | Entropy measures quantify global splicing disorders in cancer. |
| title_fullStr | Entropy measures quantify global splicing disorders in cancer. |
| title_full_unstemmed | Entropy measures quantify global splicing disorders in cancer. |
| title_short | Entropy measures quantify global splicing disorders in cancer. |
| title_sort | entropy measures quantify global splicing disorders in cancer |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18369415/?tool=EBI |
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