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TeXP: Deconvolving the effects of pervasive and autonomous transcription of transposable elements
- TeXP: Deconvolving the effects of pervasive and autonomous transcription of transposable elements
- Navarro, Fabio C. P.; Hoops, Jacob; Bellfy, Lauren; Cerveira, Eliza; Zhu, Qihui; Zhang, Chengsheng; Lee, Charles; Gerstein, Mark B.
- Ewha Authors
- Charles Lee
- SCOPUS Author ID
- Charles Lee
- Issue Date
- Journal Title
- PLOS COMPUTATIONAL BIOLOGY
- PLOS COMPUTATIONAL BIOLOGY vol. 15, no. 8
- PUBLIC LIBRARY SCIENCE
- SCIE; SCOPUS
- Document Type
- 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.
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