A comprehensive hybridization model allows whole HERV transcriptome profiling using high density microarray

Becker, Jérémie; Pérot, Philippe; Cheynet, Valérie; Oriol, Guy; Mugnier, Nathalie; Mommert, Marine; Tabone, Olivier; Textoris, Julien; Veyrieras, Jean‐Baptiste; Mallet, François

doi:10.1186/s12864-017-3669-7

Cited by 19 publications

(29 citation statements)

References 66 publications

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“…Until now, the lack of tool made difficult the exploration of HERV expression. It would be interesting to reproduce these analyses, with a more exhaustive technology designed to specifically target HERVs, like the HERV-V3 Affymetrix microarray we recently published (Becker et al 2017), or even RNAseq. It will allow us to better describe the whole HERV transcriptome modulation and understand the putative global role of HERV in the host response.…”

Section: Discussionmentioning

confidence: 99%

Endogenous retroviruses transcriptional modulation after severe infection, trauma and burn

Tabone

Mommert

Jourdan

et al. 2018

Preprint

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29 30 number of words: 5504 31 number of figures: 10 32 33 Keywords 34 Endogenous retroviruses -severe inflammatory injuries -septic shock -burn -trauma -transcriptome 35 -host response. 36 37 2 Abstract 38Although human endogenous retroviruses (HERVs) expression is a growing subject of interest, 39 no study focused before on specific endogenous retroviruses loci activation in severely injured 40 patients. Yet, HERV reactivation is observed in immunity compromised settings like some 41 cancers and auto-immune diseases. Our objective was to assess the transcriptional modulation of 42 HERVs in burn, trauma and septic shock patients. We analyzed HERV transcriptome with 43 microarray data from whole blood samples of a burn cohort (n=30), a trauma cohort (n=105) and 44 2 septic shock cohorts (n=28, n=51), and healthy volunteers (HV, n=60). We described 45 expression of the 337 probesets targeting HERV from U133 plus 2.0 microarray in each dataset 46 and then we compared HERVs transcriptional modulation of patients compared to healthy 47 volunteers. Although all 4 cohorts contained very severe patients, the majority of the 337 HERVs 48 was not expressed (around 74% in mean). Each cohort had differentially expressed probesets in 49 patients compared to HV (from 19 to 46). Strikingly, 5 HERVs were in common in all types of 50 severely injured patients, with 4 being up-modulated in patients. We highlighted co-expressed 51 profiles between HERV and nearby gene as well as autonomous HERV expression. We suggest 52 an inflammatory-specific HERV transcriptional response, and importantly, we introduce that the 53 HERVs close to immunity-related genes might have a role on its expression. 54 55 57 infected germinal cells and became integrated in our genome million years ago (Young, Stoye, 58 and Kassiotis 2013). These rare events happened several times in evolution. As retrotransposons, 59

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Section: Discussionmentioning

confidence: 99%

Endogenous retroviruses transcriptional modulation after severe infection, trauma and burn

Tabone

Mommert

Jourdan

et al. 2018

Preprint

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“…The HERV-V3 microarray targeted 353,994 loci-elements, which were represented by 4,410,200 probes [22]. The custom HERV GeneChip can discriminate distinct HERV elements through the use of a set of highly informative probesets (located in U3, R, U5 subdomains of solo, 5′ and 3′ individual LTRs and gag/pol/env regions), hereafter named the "HERV prototypes repertoire."…”

Section: Herv-v3 Processing and Analysis Custom Affymetrix Herv-v3 Gementioning

confidence: 99%

“…We have recently shown that several HERVs are expressed and modulated after septic shock and other inflammatory injuries [12]. Using the HERV-V3 microarray, which allows the measurement of HERV/MaLR at the individual locus level [22], we have also shown that HERV/MaLR are tightly modulated in peripheral blood mononuclear cells (PBMCs). We have used an ex vivo endotoxin tolerance model to mimic the septic shock host immune response [13].…”

Section: Introductionmentioning

confidence: 99%

Dynamic LTR retrotransposon transcriptome landscape in septic shock patients

et al. 2020

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Background: Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Numerous studies have explored the complex and dynamic transcriptome modulations observed in sepsis patients, but a large fraction of the transcriptome remains unexplored. This fraction could provide information to better understand sepsis pathophysiology. Multiple levels of interaction between human endogenous retroviruses (HERV) and the immune response have led us to hypothesize that sepsis is associated with HERV transcription and that HERVs may contribute to a signature among septic patients allowing stratification and personalized management. Methods: We used a high-density microarray and RT-qPCR to evaluate the HERV and Mammalian Apparent Long Terminal Repeat retrotransposons (MaLR) transcriptome in a pilot study that included 20 selected septic shock patients, stratified on mHLA-DR expression, with samples collected on day 1 and day 3 after inclusion. We validated the results in an unselected, independent cohort that included 100 septic shock patients on day 3 after inclusion. We compared septic shock patients, according to their immune status, to describe the transcriptional HERV/MaLR and conventional gene expression. For differential expression analyses, moderated t tests were performed and Wilcoxon signed-rank tests were used to analyze RT-qPCR results. Results: We showed that 6.9% of the HERV/MaLR repertoire was transcribed in the whole blood, and septic shock was associated with an early modulation of a few thousand of these loci, in comparison to healthy volunteers. We provided evidence that a subset of HERV/MaLR and conventional genes were differentially expressed in septic shock patients, according to their immune status, using monocyte HLA-DR (mHLA-DR) expression as a proxy. A group of 193 differentially expressed HERV/MaLR probesets, tested in an independent septic shock cohort, identified two groups of patients with different immune status and severity features. Conclusion: We demonstrated that a large, unexplored part of our genome, which codes for HERV/MaLR, may be linked to the host immune response. The identified set of HERV/MaLR probesets should be evaluated on a large scale to assess the relevance of these loci in the stratification of septic shock patients. This may help to address the heterogeneity of these patients.

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“…The ability to observe and quantify TE expression, especially the specific genomic locations of active elements, is crucial for understanding the molecular basis underlying a wide range of conditions and diseases(Flockerzi et al 2008). Traditional techniques for interrogating the TE transcriptome include quantitative PCR (Muradrasoli et al 2006; Rangwala et al 2009) and RNA expression microarrays (Seifarth et al 2003; Pérot et al 2012; Gnanakkan et al 2013; Young et al 2014; Becker et al 2017). However, these techniques are unable to discover elements not specifically targeted by the assay, and may fail to detect rare, previously unknown, or weakly expressed transcripts.…”

Section: Introductionmentioning

confidence: 99%

Telescope: Characterization of the retrotranscriptome by accurate estimation of transposable element expression

Bendall

Mulder

Íñiguez

et al. 2018

Preprint

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1Characterization of Human Endogenous Retrovirus (HERV) expression within the 2 transcriptomic landscape using RNA-seq is complicated by uncertainty in fragment 3 assignment because of sequence similarity. We present Telescope, a computational 4 software tool that provides accurate estimation of transposable element expression 5 (retrotranscriptome) resolved to specific genomic locations. Telescope directly addresses 6 uncertainty in fragment assignment by reassigning ambiguously mapped fragments to the 7 most probable source transcript as determined within a Bayesian statistical model. We 8 demonstrate the utility of our approach through single locus analysis of HERV expression 9 in 13 ENCODE cell types. When examined at this resolution, we find that the magnitude 10

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A comprehensive hybridization model allows whole HERV transcriptome profiling using high density microarray

Cited by 19 publications

References 66 publications

Endogenous retroviruses transcriptional modulation after severe infection, trauma and burn

Endogenous retroviruses transcriptional modulation after severe infection, trauma and burn

Dynamic LTR retrotransposon transcriptome landscape in septic shock patients

Telescope: Characterization of the retrotranscriptome by accurate estimation of transposable element expression

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