Identification of introns harboring functional sequence elements through positional conservation

Abstract Many human introns carry out a function, in the sense that they are critical to maintain normal cellular activity. Their identification is fundamental to understanding cellular processes and disease. However, being noncoding elements, such functional introns are poorly predicted based on tr...

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Autores principales:	Michal Chorev, Alan Joseph Bekker, Jacob Goldberger, Liran Carmel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f3aa411fbf434940a0592dae1ca30951
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spelling	oai:doaj.org-article:f3aa411fbf434940a0592dae1ca309512021-12-02T11:53:09ZIdentification of introns harboring functional sequence elements through positional conservation10.1038/s41598-017-04476-02045-2322https://doaj.org/article/f3aa411fbf434940a0592dae1ca309512017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04476-0https://doaj.org/toc/2045-2322Abstract Many human introns carry out a function, in the sense that they are critical to maintain normal cellular activity. Their identification is fundamental to understanding cellular processes and disease. However, being noncoding elements, such functional introns are poorly predicted based on traditional approaches of sequence and structure conservation. Here, we generated a dataset of human functional introns that carry out different types of functions. We showed that functional introns share common characteristics, such as higher positional conservation along the coding sequence and reduced loss rates, regardless of their specific function. A unique property of the data is that if an intron is unknown to be functional, it still does not mean that it is indeed non-functional. We developed a probabilistic framework that explicitly accounts for this unique property, and predicts which specific human introns are functional. We show that we successfully predict function even when the algorithm is trained on introns with a different type of function. This ability has many implications in studying regulatory networks, gene regulation, the effect of mutations outside exons on human disease, and on our general understanding of intron evolution and their functional exaptation in mammals.Michal ChorevAlan Joseph BekkerJacob GoldbergerLiran CarmelNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michal Chorev Alan Joseph Bekker Jacob Goldberger Liran Carmel Identification of introns harboring functional sequence elements through positional conservation
description	Abstract Many human introns carry out a function, in the sense that they are critical to maintain normal cellular activity. Their identification is fundamental to understanding cellular processes and disease. However, being noncoding elements, such functional introns are poorly predicted based on traditional approaches of sequence and structure conservation. Here, we generated a dataset of human functional introns that carry out different types of functions. We showed that functional introns share common characteristics, such as higher positional conservation along the coding sequence and reduced loss rates, regardless of their specific function. A unique property of the data is that if an intron is unknown to be functional, it still does not mean that it is indeed non-functional. We developed a probabilistic framework that explicitly accounts for this unique property, and predicts which specific human introns are functional. We show that we successfully predict function even when the algorithm is trained on introns with a different type of function. This ability has many implications in studying regulatory networks, gene regulation, the effect of mutations outside exons on human disease, and on our general understanding of intron evolution and their functional exaptation in mammals.
format	article
author	Michal Chorev Alan Joseph Bekker Jacob Goldberger Liran Carmel
author_facet	Michal Chorev Alan Joseph Bekker Jacob Goldberger Liran Carmel
author_sort	Michal Chorev
title	Identification of introns harboring functional sequence elements through positional conservation
title_short	Identification of introns harboring functional sequence elements through positional conservation
title_full	Identification of introns harboring functional sequence elements through positional conservation
title_fullStr	Identification of introns harboring functional sequence elements through positional conservation
title_full_unstemmed	Identification of introns harboring functional sequence elements through positional conservation
title_sort	identification of introns harboring functional sequence elements through positional conservation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f3aa411fbf434940a0592dae1ca30951
work_keys_str_mv	AT michalchorev identificationofintronsharboringfunctionalsequenceelementsthroughpositionalconservation AT alanjosephbekker identificationofintronsharboringfunctionalsequenceelementsthroughpositionalconservation AT jacobgoldberger identificationofintronsharboringfunctionalsequenceelementsthroughpositionalconservation AT lirancarmel identificationofintronsharboringfunctionalsequenceelementsthroughpositionalconservation
_version_	1718394902509780992

Identification of introns harboring functional sequence elements through positional conservation

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