Biology subjects

Wucher, V.

Publications and source records attributed to Wucher, V..

8 recordsLinked to original sources

bioRxiv2025

Detecting aberrant splicing events in short-read RNA-seq with SAMI, an UMI-aware Nextflow pipeline

SummaryDespite RNA-sequencing solutions have existed for 15 years, successfully replacing micro-arrays for gene expression profiling, their potential to analyse splicing is still to be achieved in clinical settings. Powerful tools were developed to quantify known iso-forms, to compare sample groups or to identify outliers in large datasets, but most fail to address the most common situation in routine diagnostics: identifying non-recurring events in low-dimension data. To fill this gap, we developed SAMI (Splicing Analysis with Molecular Indexes), an UMI-aware pipeline focusing on splicing events which differ from provided annotation. The ability of SAMI and concurrent software to detect intragenic splicing aberrations and gene fusions was assessed, both on real data from a commercial control sample and simulated data generated with ASimulatoR. Availability and ImplementationNextflow pipeline and Singularity container recipe freely available under GPL 3 licence at https://github.com/HCL-HUBL/SAMI Contactsylvain.mareschal@chu-lyon.fr

bioinformatics↗

bioRxiv2021

Brain transcriptomic profiling reveals common alterations across neurodegenerative and psychiatric disorders

Neurodegenerative and neuropsychiatric disorders (ND-NPs) are multifactorial, polygenic and complex behavioral phenotypes caused by brain abnormalities. Large-scale collaborative efforts have tried to identify the genetic architecture of these conditions. However, specific and shared underlying molecular pathobiology of brain illnesses is not clear. Here, we examine transcriptome-wide characterization of eight conditions, using a total of 2,633 post-mortem brain samples from patients with Alzheimers disease (AD), Parkinsons disease (PD), Progressive Supranuclear Palsy (PSP), Pathological Aging (PA), Autism Spectrum Disorder (ASD), Schizophrenia (Scz), Major Depressive Disorder (MDD), and Bipolar Disorder (BP)-in comparison with 2,078 brain samples from matched control subjects. Similar transcriptome alterations were observed between NDs and NPs with the top correlations obtained between Scz-BP, ASD-PD, AD-PD, and Scz-ASD. Region-specific comparisons also revealed shared transcriptome alterations in frontal and temporal lobes across NPs and NDs. Co-expression network analysis identified coordinated dysregulations of cell-type-specific modules across NDs and NPs. This study provides a transcriptomic framework to understand the molecular alterations of NPs and NDs through their shared- and specific gene expression in the brain.

neuroscience↗

bioRxiv2021

Day-night and seasonal variation of human gene expression across tissues

Circadian and circannual cycles trigger physiological changes whose reflection on human transcriptomes remains largely uncharted. We used the time and season of death of 932 individuals from GTEx to jointly investigate transcriptomic changes associated with those cycles across multiple tissues. Overall, most variation across tissues during day-night and among seasons was unique to each cycle. Although all tissues remodeled their transcriptomes, brain and gonadal tissues exhibited the highest seasonality, whereas those in the thoracic cavity showed stronger day-night regulation. Core clock genes displayed marked day-night differences across multiple tissues, which were largely conserved in baboon and mouse, but adapted to their nocturnal or diurnal habits. Seasonal variation of expression affected multiple pathways and it was enriched among genes associated with the immune response, consistent with the seasonality of viral infections. Furthermore, they unveiled cytoarchitectural changes in brain regions. Altogether, our results provide the first combined atlas of how transcriptomes from human tissues adapt to major cycling environmental conditions.

genomics↗

bioRxiv2019

A limited set of transcriptional programs define major histological types and provide the molecular basis for a cellular taxonomy of the human body

We have produced RNA sequencing data for a number of primary cells from different locations in the human body. The clustering of these primary cells reveals that most cells in the human body share a few broad transcriptional programs, which define five major cell types: epithelial, endothelial, mesenchymal, neural and blood cells. These act as basic components of many tissues and organs. Based on gene expression, these cell types redefine the basic histological types by which tissues have been traditionally classified. We identified genes whose expression is specific to these cell types, and from these genes, we estimated the contribution of the major cell types to the composition of human tissues. We found this cellular composition to be a characteristic signature of tissues, and to reflect tissue morphological heterogeneity and histology. We identified changes in cellular composition in different tissues associated with age and sex and found that departures from the normal cellular composition correlate with histological phenotypes associated to disease. One Sentence SummaryA few broad transcriptional programs define the major cell types underlying the histology of human tissues and organs.

genomics↗

bioRxiv2019

Cell type specific genetic regulation of gene expression across human tissues

The Genotype-Tissue Expression (GTEx) project has identified expression and splicing quantitative trait loci (cis-QTLs) for the majority of genes across a wide range of human tissues. However, the interpretation of these QTLs has been limited by the heterogeneous cellular composition of GTEx tissue samples. Here, we map interactions between computational estimates of cell type abundance and genotype to identify cell type interaction QTLs for seven cell types and show that cell type interaction eQTLs provide finer resolution to tissue specificity than bulk tissue cis-eQTLs. Analyses of genetic associations to 87 complex traits show a contribution from cell type interaction QTLs and enables the discovery of hundreds of previously unidentified colocalized loci that are masked in bulk tissue.\n\nOne Sentence SummaryEstimated cell type abundances from bulk RNA-seq across tissues reveal the cellular specificity of quantitative trait loci.

genomics↗

bioRxiv2019

The GTEx Consortium atlas of genetic regulatory effects across human tissues

The Genotype-Tissue Expression (GTEx) project was established to characterize genetic effects on the transcriptome across human tissues, and to link these regulatory mechanisms to trait and disease associations. Here, we present analyses of the v8 data, based on 17,382 RNA-sequencing samples from 54 tissues of 948 post-mortem donors. We comprehensively characterize genetic associations for gene expression and splicing in cis and trans, showing that regulatory associations are found for almost all genes, and describe the underlying molecular mechanisms and their contribution to allelic heterogeneity and pleiotropy of complex traits. Leveraging the large diversity of tissues, we provide insights into the tissue-specificity of genetic effects, and show that cell type composition is a key factor in understanding gene regulatory mechanisms in human tissues.

genetics↗

bioRxiv2019

Selection following gene duplication shapes recent genome evolution in the pea aphid Acyrthosiphon pisum

Ecology of insects is as wide as their diversity, which reflects their high capacity of adaptation in most of the environments of our planet. Aphids, with over 4,000 species, have developed a series of adaptations including a high phenotypic plasticity and the ability to feed on the phloem-sap of plants, which is enriched in sugars derived from photosynthesis. Recent analyses of aphid genomes have indicated a high level of shared ancestral gene duplications that might represent a basis for genetic innovation and broad adaptations. In addition, there is a large number of recent, species-specific gene duplications whose role in adaptation remains poorly understood. Here, we tested whether duplicates specific to the pea aphid Acyrthosiphon pisum are related to genomic innovation by combining comparative genomics, transcriptomics, and chromatin accessibility analyses. Consistent with large levels of neofunctionalization, we found that most of the recent pairs of gene duplicates evolved asymmetrically, showing divergent patterns of positive selection and gene expression. Genes under selection involved a plethora of biological functions, suggesting that neofunctionalization and tissue specificity, among other evolutionary mechanisms, have orchestrated the evolution of recent paralogs in the pea aphid and may have facilitated host-symbiont cooperation. Our comprehensive phylogenomics analysis allowed to tackle the history of duplicated genes to pave the road towards understanding the role of gene duplication in ecological adaptation.

genomics↗

bioRxiv2018

Characterisation and functional predictions of canine long non-coding RNAs

Long non-coding RNAs (lncRNAs) are a family of heterogeneous RNAs that play major roles in multiple biological processes. We recently identified an extended repertoire of more than 10,000 lncRNAs of the domestic dog however, predicting their biological functionality remains challenging. In this study, we have characterised the expression profiles of 10,444 canine lncRNAs in 26 distinct tissue types, representing various anatomical systems. We showed that lncRNA expressions are mainly clustered by tissue type and we highlighted that 44% of canine lncRNAs are expressed in a tissue-specific manner. We further demonstrated that tissue-specificity correlates with specific families of canine transposable elements. In addition, we identified more than 900 conserved dog-human lncRNAs for which we show their overall reproducible expression patterns between dog and humans through comparative transcriptomics. Finally, co-expression analyses of lncRNA and neighbouring protein-coding genes identified more than 3,400 canine lncRNAs, suggesting that functional roles of these lncRNAs act as regulatory elements. Altogether, this genomic and transcriptomic integrative study of lncRNAs constitutes a major resource to investigate genotype to phenotype relationships and biomedical research in the dog species.

genomics↗