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...

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Autores principales:	William Ritchie, Samuel Granjeaud, Denis Puthier, Daniel Gautheret
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d886706782b84fa8b4c3d3b123862386
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spelling	oai:doaj.org-article:d886706782b84fa8b4c3d3b1238623862021-11-25T05:41:23ZEntropy measures quantify global splicing disorders in cancer.1553-734X1553-735810.1371/journal.pcbi.1000011https://doaj.org/article/d886706782b84fa8b4c3d3b1238623862008-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18369415/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Most 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.William RitchieSamuel GranjeaudDenis PuthierDaniel GautheretPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 4, Iss 3, p e1000011 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 William Ritchie Samuel Granjeaud Denis Puthier Daniel Gautheret Entropy measures quantify global splicing disorders in cancer.
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.
format	article
author	William Ritchie Samuel Granjeaud Denis Puthier Daniel Gautheret
author_facet	William Ritchie Samuel Granjeaud Denis Puthier Daniel Gautheret
author_sort	William Ritchie
title	Entropy measures quantify global splicing disorders in cancer.
title_short	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_sort	entropy measures quantify global splicing disorders in cancer.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/d886706782b84fa8b4c3d3b123862386
work_keys_str_mv	AT williamritchie entropymeasuresquantifyglobalsplicingdisordersincancer AT samuelgranjeaud entropymeasuresquantifyglobalsplicingdisordersincancer AT denisputhier entropymeasuresquantifyglobalsplicingdisordersincancer AT danielgautheret entropymeasuresquantifyglobalsplicingdisordersincancer
_version_	1718414547164856320

Entropy measures quantify global splicing disorders in cancer.

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