TypeTE: a tool to genotype mobile element insertions from whole genome resequencing data

Goubert, Clément; Thomas, Jainy; Payer, Lindsay M.; Kidd, Jeffrey M.; Feusier, Julie E.; Watkins, W. Scott; Burns, Kathleen H.; Jorde, Lynn B.; Feschotte, Cédric

doi:10.1101/791665

Cited by 6 publications

(14 citation statements)

References 65 publications

(98 reference statements)

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“…There are at least four important methodological differences that could account for the discrepancies between the two studies. First and foremost, our analysis considered 860 reference TEs never analysed before, presumably because their genotypes could not be confidently predicted [31]. Second, we used improved genotypes recalled by TypeTE [31], while Wang et al used the genotypes as originally called by Sudmant et al [12].…”

Section: (A) Mapping Cis-te-eqtl In Lcl and Ipscmentioning

confidence: 99%

Contribution of unfixed transposable element insertions to human regulatory variation

Goubert

Zevallos

Feschotte

2020

Phil. Trans. R. Soc. B

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Thousands of unfixed transposable element (TE) insertions segregate in the human population, but little is known about their impact on genome function. Recently, a few studies associated unfixed TE insertions to mRNA levels of adjacent genes, but the biological significance of these associations, their replicability across cell types and the mechanisms by which they may regulate genes remain largely unknown. Here, we performed a TE-expression QTL analysis of 444 lymphoblastoid cell lines (LCL) and 289 induced pluripotent stem cells using a newly developed set of genotypes for 2743 polymorphic TE insertions. We identified 211 and 176 TE-eQTL acting in cis in each respective cell type. Approximately 18% were shared across cell types with strongly correlated effects. Furthermore, analysis of chromatin accessibility QTL in a subset of the LCL suggests that unfixed TEs often modulate the activity of enhancers and other distal regulatory DNA elements, which tend to lose accessibility when a TE inserts within them. We also document a case of an unfixed TE likely influencing gene expression at the post-transcriptional level. Our study points to broad and diverse cis -regulatory effects of unfixed TEs in the human population and underscores their plausible contribution to phenotypic variation. This article is part of a discussion meeting issue ‘Crossroads between transposons and gene regulation’.

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Section: (A) Mapping Cis-te-eqtl In Lcl and Ipscmentioning

confidence: 99%

Contribution of unfixed transposable element insertions to human regulatory variation

Goubert

Zevallos

Feschotte

2020

Phil. Trans. R. Soc. B

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“…Though the overall performance of MELT outperformed existing MEI discovery tools (Gardner et al 2017) and it has been successfully used in several large-scale studies (Gardner et al 2017, 2019; Feusier et al 2019; Werling et al 2018; Torene et al 2020), but the detection power could be compromised by modest sequencing depth and incompetence in complex genomic regions of short-read WGS etc . In addition, the overall genotyping accuracy by MELT v2 was 87.95% for non-reference Alu s (not excluding MEIs in low complexity regions), when compared with PCR generated genotypes (Goubert et al 2020). As such, we have tried to ensure the site quality by strict filtering.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide analysis of mobile element insertions in human genomes

Niu

Teng

et al. 2021

Preprint

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Mobile element insertions (MEIs) are a major class of structural variants (SVs) and have been linked to many human genetic disorders, including hemophilia, neurofibromatosis, and various cancers. However, human MEI resources from large-scale genome sequencing are still lacking compared to those for SNPs and SVs. Here, we report a comprehensive map of 36,699 non-reference MEIs constructed from 5,675 genomes, comprising 2,998 Chinese samples (∼26.2X, NyuWa) and 2,677 samples from the 1000 Genomes Project (∼7.4X, 1KGP). We discovered that LINE-1 insertions were highly enriched at centromere regions, implying the role of chromosome context in retroelement insertion. After functional annotation, we estimated that MEIs are responsible for about 9.3% of all protein-truncating events per genome. Finally, we built a companion database named HMEID for public use. This resource represents the latest and largest genomewide study on MEIs and will have broad utility for exploration of human MEI findings.

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“…Mapping quality [56] greater than 20 was required in both cases. This approach facilitated targeted analysis of user-defined integrations and reduced computational burden by first aligning to a limited reference sequence set rather than the entire genome, as in other recent analogous approaches [57,58].…”

Section: Bioinformatic Detection Of Alve Integration Sitesmentioning

confidence: 99%

Identification and characterisation of endogenous Avian Leukosis Virus subgroup E (ALVE) insertions in chicken whole genome sequencing data

et al. 2020

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Background: Endogenous retroviruses (ERVs) are the remnants of retroviral infections which can elicit prolonged genomic and immunological stress on their host organism. In chickens, endogenous Avian Leukosis Virus subgroup E (ALVE) expression has been associated with reductions in muscle growth rate and egg production, as well as providing the potential for novel recombinant viruses. However, ALVEs can remain in commercial stock due to their incomplete identification and association with desirable traits, such as ALVE21 and slow feathering. The availability of whole genome sequencing (WGS) data facilitates high-throughput identification and characterisation of these retroviral remnants. Results: We have developed obsERVer, a new bioinformatic ERV identification pipeline which can identify ALVEs in WGS data without further sequencing. With this pipeline, 20 ALVEs were identified across eight elite layer lines from Hy-Line International, including four novel integrations and characterisation of a fast feathered phenotypic revertant that still contained ALVE21. These bioinformatically detected sites were subsequently validated using new highthroughput KASP assays, which showed that obsERVer was highly precise and exhibited a 0% false discovery rate. A further fifty-seven diverse chicken WGS datasets were analysed for their ALVE content, identifying a total of 322 integration sites, over 80% of which were novel. Like exogenous ALV, ALVEs show site preference for proximity to protein-coding genes, but also exhibit signs of selection against deleterious integrations within genes. Conclusions: obsERVer is a highly precise and broadly applicable pipeline for identifying retroviral integrations in WGS data. ALVE identification in commercial layers has aided development of high-throughput diagnostic assays which will aid ALVE management, with the aim to eventually eradicate ALVEs from high performance lines. Analysis of non-commercial chicken datasets with obsERVer has revealed broad ALVE diversity and facilitates the study of the biological effects of these ERVs in wild and domesticated populations.

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TypeTE: a tool to genotype mobile element insertions from whole genome resequencing data

Cited by 6 publications

References 65 publications

Contribution of unfixed transposable element insertions to human regulatory variation

Contribution of unfixed transposable element insertions to human regulatory variation

Genome-wide analysis of mobile element insertions in human genomes

Identification and characterisation of endogenous Avian Leukosis Virus subgroup E (ALVE) insertions in chicken whole genome sequencing data

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