Search bioRxiv⌕ Search

Biology subjects

Bohl-Viallefond, G.

Publications and source records attributed to Bohl-Viallefond, G..

3 recordsLinked to original sources

AnalyzAIRR: A user-friendly guided workflow for AIRR data analysis

The analysis of bulk adaptive immune receptor repertoires (AIRR) enables the understanding of immune responses in both normal and pathological conditions. However, the complexity of AIRR calls for advanced, specialized methods to extract meaningful biological insights. These sophisticated approaches often present challenges for researchers with limited bioinformatics expertise, hindering access to comprehensive immune system analysis. To address this challenge, we developed AnalyzAIRR, an AIRR-compliant R package enabling advanced bulk AIRR sequencing data. The tool integrates state-of-the-art statistical and visualization methods applicable at various levels of granularity. It offers a platform for general data exploration, filtering and manipulation, and in-depth cross-comparisons of AIRR datasets, aimed at answering specific biological questions. We illustrate AnalyzAIRR functionalities using of a published murine dataset of 18 T-cell receptor repertoires from three diferrent T cell subsets. We first detected and removed a major contaminant in a group of samples, before proceeding with to the comparative analysis. Subsequent cross-sample analysis revealed differences in repertoire diversity that aligned with the respective cell phenotypes, and in repertoire convergence among the studied subsets. AnalyzAIRRs set of analytical metrics is integrated into a Shiny web application and complemented with a tutorial to help users in their analytical strategy, making it user-friendly for biologists with little or no background in bioinformatics.

bioinformatics↗

Transposable elements are prevalent vectors of transgenerational epigenetic inheritance in nature

Loss of DNA methylation over transposable elements (TEs) can affect neighboring genes and be epigenetically inherited in plants, yet the determinants and significance of this additional system of inheritance are unknown. Here, we demonstrate at thousands of TE loci across the Arabidopsis thaliana genome, that experimentally-induced hypomethylation can be transmitted transgenerationally and reveal the role of small RNAs derived from related copies in counteracting this transmission. Using data from >700 strains collected worldwide, we uncover natural hypomethylation at hundreds of the same TE loci, often situated near stress-responsive genes. Like their experimental counterparts, most natural epivariants we tested can be inherited without DNA sequence changes and are therefore bona fide epialleles, although genetic factors modulate their recurrence or persistence. Crucially, we demonstrate that TE-mediated epiallelic variation associated with differential gene expression is generally causal and may be target of selection in specific environments, thus establishing its importance in nature.

genomics↗

PTGS is dispensable for the initiation of epigenetic silencing of an active transposon in Arabidopsis

Transposable elements (TEs) are largely repressed in plants through transcriptional gene silencing (TGS), which is maintained by heritable epigenetic silencing marks such as DNA methylation. However, the mechanisms by which silencing is installed in the first place remains poorly understood in plants. Small interfering (si)RNAs and post-transcriptional gene silencing (PTGS) play a role in the initial response by reducing mRNA and protein levels of active TEs and are believed to mediate the initiation of TGS by guiding the first deposition of DNA methylation. To determine how this silencing installation works, we took advantage of EVADE (EVD), an endogenous retroelement in Arabidopsis, which can be used to recapitulate true de novo silencing with a well-established sequence of PTGS followed by a TGS phase. To test whether PTGS is a prerequisite for TGS, active EVD copies were introduced into RNA-DEPENDENT-RNA-POLYMERASE-6 (RDR6) mutants lacking an essential PTGS component. EVD activity and silencing were monitored across several generations. Unexpectedly, even in the absence of PTGS, TGS and silencing of EVD were still achieved through installation of RNA-directed DNA methylation (RdDM) at EVD regulatory sequences without any prior DNA methylation at its coding sequence. Hence, our study shows that PTGS is dispensable for de novo EVD silencing. Although we cannot rule out that PTGS might facilitate the initiation of TGS, or control TE activity until then, initiation of epigenetic silencing can take place in its absence.

plant biology↗