TeXP: Deconvolving the effects of pervasive and autonomous transcription of transposable elements.

The Long interspersed nuclear element 1 (LINE-1) is a primary source of genetic variation in humans and other mammals. Despite its importance, LINE-1 activity remains difficult to study because of its highly repetitive nature. Here, we developed and validated a method called TeXP to gauge LINE-1 act...

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Main Authors: Fabio Cp Navarro, Jacob Hoops, Lauren Bellfy, Eliza Cerveira, Qihui Zhu, Chengsheng Zhang, Charles Lee, Mark B Gerstein
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-08-01
Series:PLoS Computational Biology
Online Access:https://doi.org/10.1371/journal.pcbi.1007293
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spelling doaj-b1a0c964206349c9a372f5c237d064e92021-04-21T15:38:24ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582019-08-01158e100729310.1371/journal.pcbi.1007293TeXP: Deconvolving the effects of pervasive and autonomous transcription of transposable elements.Fabio Cp NavarroJacob HoopsLauren BellfyEliza CerveiraQihui ZhuChengsheng ZhangCharles LeeMark B GersteinThe Long interspersed nuclear element 1 (LINE-1) is a primary source of genetic variation in humans and other mammals. Despite its importance, LINE-1 activity remains difficult to study because of its highly repetitive nature. Here, we developed and validated a method called TeXP to gauge LINE-1 activity accurately. TeXP builds mappability signatures from LINE-1 subfamilies to deconvolve the effect of pervasive transcription from autonomous LINE-1 activity. In particular, it apportions the multiple reads aligned to the many LINE-1 instances in the genome into these two categories. Using our method, we evaluated well-established cell lines, cell-line compartments and healthy tissues and found that the vast majority (91.7%) of transcriptome reads overlapping LINE-1 derive from pervasive transcription. We validated TeXP by independently estimating the levels of LINE-1 autonomous transcription using ddPCR, finding high concordance. Next, we applied our method to comprehensively measure LINE-1 activity across healthy somatic cells, while backing out the effect of pervasive transcription. Unexpectedly, we found that LINE-1 activity is present in many normal somatic cells. This finding contrasts with earlier studies showing that LINE-1 has limited activity in healthy somatic tissues, except for neuroprogenitor cells. Interestingly, we found that the amount of LINE-1 activity was associated with the with the amount of cell turnover, with tissues with low cell turnover rates (e.g. the adult central nervous system) showing lower LINE-1 activity. Altogether, our results show how accounting for pervasive transcription is critical to accurately quantify the activity of highly repetitive regions of the human genome.https://doi.org/10.1371/journal.pcbi.1007293
collection DOAJ
language English
format Article
sources DOAJ
author Fabio Cp Navarro
Jacob Hoops
Lauren Bellfy
Eliza Cerveira
Qihui Zhu
Chengsheng Zhang
Charles Lee
Mark B Gerstein
spellingShingle Fabio Cp Navarro
Jacob Hoops
Lauren Bellfy
Eliza Cerveira
Qihui Zhu
Chengsheng Zhang
Charles Lee
Mark B Gerstein
TeXP: Deconvolving the effects of pervasive and autonomous transcription of transposable elements.
PLoS Computational Biology
author_facet Fabio Cp Navarro
Jacob Hoops
Lauren Bellfy
Eliza Cerveira
Qihui Zhu
Chengsheng Zhang
Charles Lee
Mark B Gerstein
author_sort Fabio Cp Navarro
title TeXP: Deconvolving the effects of pervasive and autonomous transcription of transposable elements.
title_short TeXP: Deconvolving the effects of pervasive and autonomous transcription of transposable elements.
title_full TeXP: Deconvolving the effects of pervasive and autonomous transcription of transposable elements.
title_fullStr TeXP: Deconvolving the effects of pervasive and autonomous transcription of transposable elements.
title_full_unstemmed TeXP: Deconvolving the effects of pervasive and autonomous transcription of transposable elements.
title_sort texp: deconvolving the effects of pervasive and autonomous transcription of transposable elements.
publisher Public Library of Science (PLoS)
series PLoS Computational Biology
issn 1553-734X
1553-7358
publishDate 2019-08-01
description The Long interspersed nuclear element 1 (LINE-1) is a primary source of genetic variation in humans and other mammals. Despite its importance, LINE-1 activity remains difficult to study because of its highly repetitive nature. Here, we developed and validated a method called TeXP to gauge LINE-1 activity accurately. TeXP builds mappability signatures from LINE-1 subfamilies to deconvolve the effect of pervasive transcription from autonomous LINE-1 activity. In particular, it apportions the multiple reads aligned to the many LINE-1 instances in the genome into these two categories. Using our method, we evaluated well-established cell lines, cell-line compartments and healthy tissues and found that the vast majority (91.7%) of transcriptome reads overlapping LINE-1 derive from pervasive transcription. We validated TeXP by independently estimating the levels of LINE-1 autonomous transcription using ddPCR, finding high concordance. Next, we applied our method to comprehensively measure LINE-1 activity across healthy somatic cells, while backing out the effect of pervasive transcription. Unexpectedly, we found that LINE-1 activity is present in many normal somatic cells. This finding contrasts with earlier studies showing that LINE-1 has limited activity in healthy somatic tissues, except for neuroprogenitor cells. Interestingly, we found that the amount of LINE-1 activity was associated with the with the amount of cell turnover, with tissues with low cell turnover rates (e.g. the adult central nervous system) showing lower LINE-1 activity. Altogether, our results show how accounting for pervasive transcription is critical to accurately quantify the activity of highly repetitive regions of the human genome.
url https://doi.org/10.1371/journal.pcbi.1007293
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