L1EM: A tool for accurate locus specific LINE-1 RNA quantification

McKerrow, Wilson; Fenyö, David

doi:10.1101/714014

Cited by 5 publications

(9 citation statements)

References 34 publications

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“…Similarly, L1 elements have a weak polyadenylation signal, leading to a significant fraction of 3' readthrough 63,64 . The fraction of these 3'-extended L1 RNAs varies and might depend on the poly(dA) length of the element 65 . These extended RNA species can be used as a template for reverse transcription as efficiently as unit-length transcripts, leading to the retrotransposition of sequences derived from L1 3' flank to new genomic locations (3' transduction) 64,66,67 .…”

Section: Te Transcripts Used As Template For Reverse Transcription Retrotransposon Transcriptionmentioning

confidence: 99%

“…It is currently unclear if all L1HS loci have the potential to generate 3'-readthrough, which may represent a limitation of this approach. Indeed, some L1HS loci can be identified by L1EM 65 , a software focused on L1 and based on the EM algorithm, as expressed but without readthrough in the flanking sequence. Nevertheless, it is also possible that these reads actually originated from related non-reference insertions not represented in the L1EM index and were thus misplaced.…”

Section: Te Sequence and Insertional Polymorphismsmentioning

confidence: 99%

“…REdiscoverTE explicitly models autonomous and co-transcripts in the indexed transcriptome for Salmon pseudo-alignment 153 . Finally, L1EM includes models for autonomous sense and antisense transcriptions, passive co-transcription and 3' readthrough at each locus and can provide locus-specific expression values 65 (Fig. 4c).…”

Section: Co-transcription and Pervasive Transcriptionmentioning

confidence: 99%

“…Quantification is obtained for each TE locus and for each associated transcript isoform (e.g. L1EM65 ).…”

mentioning

confidence: 99%

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Measuring and interpreting transposable element expression

2020

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Transposable elements (TEs) are insertional mutagens that contribute greatly to the plasticity of eukaryotic genomes, influencing the evolution and adaptation of species as well as physiology or disease in individuals. Measuring TE expression helps to understand not only when and where TE mobilization can occur, but also how this process alters gene expression, chromatin accessibility or cellular signalling pathways. Although genome-wide gene expression assays such as RNA-sequencing include transposon-derived transcripts, the majority of computational analytical tools discard or misinterpret TE-derived reads. Emerging approaches are improving the identification of expressed TE loci and helping to discriminate TE transcripts that permit TE mobilization from gene-TE chimeric transcripts or pervasive transcription. Here, we review the main challenges associated with the detection of TE expression, including mappability, insertional and internal sequence polymorphisms, and the diversity of the TE transcriptional landscape, as well as the different experimental and computational strategies to solve them.

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Section: Te Transcripts Used As Template For Reverse Transcription Retrotransposon Transcriptionmentioning

confidence: 99%

Section: Te Sequence and Insertional Polymorphismsmentioning

confidence: 99%

Section: Co-transcription and Pervasive Transcriptionmentioning

confidence: 99%

“…Quantification is obtained for each TE locus and for each associated transcript isoform (e.g. L1EM65 ).…”

mentioning

confidence: 99%

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Measuring and interpreting transposable element expression

2020

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“…All are poly A enriched and strand specific. We used L1EM 16 to identify the expression of full-length mRNAs from the active LINE-1 subfamily (L1Hs) in these samples. Primary keratinocyte (KC) cultures had the highest LINE-1 expression at 4.7 fragments per million (FPM) on average in this dataset.…”

Section: Resultsmentioning

confidence: 99%

LINE-1 Retrotransposon expression in cancerous, epithelial and neuronal cells revealed by 5’ single-cell RNA-Seq

McKerrow

Evans

Rocha

et al. 2021

Preprint

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LINE-1 retrotransposons are known to be expressed in early development, in tumors and in the germline. Less is known about LINE-1 expression at the single cell level, especially outside the context of cancer. Because LINE-1 elements are present at a high copy number, many transcripts that are not driven by the LINE-1 promoter nevertheless terminate at the LINE-1 3’ UTR. Thus, 3’ targeted single cell RNA-seq datasets are not appropriate for studying LINE-1. However, 5’ targeted single cell datasets provide an opportunity to analyze LINE-1 expression at the single cell level. Most LINE-1 copies are 5’ truncated, and a transcript that contains the LINE-1 5’ UTR as its 5’ end is likely to have been transcribed from its promoter. We developed a method, L1-sc (LINE-1 expression for single cells), to quantify LINE-1 expression in 5’ targeted 10x genomics single cell RNA-seq datasets. Our method confirms that LINE-1 expression is high in cancer cells, but low or absent from immune cells. We also find that LINE-1 expression is elevated in epithelial compared to immune cells outside of the context of cancer and that it is also elevated in neurons compared to glia in the mouse hippocampus.

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Locus-specific chromatin profiling of evolutionarily young transposable elements

Taylor

Lowe

Philippe

et al. 2021

Preprint

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Despite a vast expansion in the availability of epigenomic data, our knowledge of the chromatin landscape at interspersed repeats remains highly limited by difficulties in mapping short-read sequencing data to these regions. In particular, little is known about the locus-specific regulation of evolutionarily young transposable elements (TEs), which have been implicated in genome stability, gene regulation and innate immunity in a variety of developmental and disease contexts. Here we propose an approach for generating locus-specific protein-DNA binding profiles at interspersed repeats, which leverages information on the spatial proximity between repetitive and non-repetitive genomic regions. We demonstrate that the combination of HiChIP and a newly developed mapping tool (PAtChER) yields accurate protein enrichment profiles at individual repetitive loci. Using this approach, we reveal previously unappreciated variation in the epigenetic profiles of young TE loci in mouse and human cells. Insights gained using our method will be invaluable for dissecting the molecular determinants of TE regulation and their impact on the genome.

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L1EM: A tool for accurate locus specific LINE-1 RNA quantification

Cited by 5 publications

References 34 publications

Measuring and interpreting transposable element expression

Measuring and interpreting transposable element expression

LINE-1 Retrotransposon expression in cancerous, epithelial and neuronal cells revealed by 5’ single-cell RNA-Seq

Locus-specific chromatin profiling of evolutionarily young transposable elements

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