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Biology subjects

Robert, E.

Publications and source records attributed to Robert, E..

3 recordsLinked to original sources

Deciphering the genetic basis of phytoplankton traits through genome-wide association studies

Recently, an inventory of genes in phytoplankton was conducted through expeditions such as TARA Oceans. Approximately 1.5 million genes were identified, of which at least three-quarters have unknown function. Presently, a several research programmes are engaged in the sequencing of marine biodiversity, resulting in a rapid expansion of genomic databases. Access to the genomic sequences of these organisms will soon be readily accessible to the scientific community. Although analysing this data is promising, the characterization of genes or genomes, on the other hand, is progressing very slowly and remains a major challenge for scientists. The aim of this study was to use GWAS approaches to decipher genomic loci without a priori assumptions. The microalga Tisochrysis lutea was selected as a case study due to its economic importance and the extensive knowledge accumulated over the years. Particular attention was paid to pigment and lipid metabolism due to their high commercial value. To implement the GWAS approach, a collection of algal lineages was established (100 lineages) from available polyclonal strains (15 strains). This collection was then phenotyped under two different culture conditions. Of the 31 phenotypic traits investigated, 18 met the requirements for GWAS analysis. Concurrently, each algal lineage was genotyped by whole genome sequencing to inventory all genetic polymorphisms. A mixed model was applied, revealing 13 significant associations between phenotypic traits and alleles. These associations highlight previously unsuspected genomic loci that play a major role in pigment or lipid content. Genes identified at these loci may have a direct or indirect role in these metabolic pathways. Nevertheless, elucidating the molecular mechanisms of the associated genes remains limited without the implementation of functional approaches. Despite the complexity of the process, we conclude that the GWAS approach was effective for deciphering phytoplankton genomes, particularly for quantitative traits of interest. Ideally, this approach should be combined with other functional methods to progressively decode marine genomes.

genetics↗

Testing genomic offset with common gardens in genetically structured black spruce (Picea mariana)

Boreal forests play a crucial role in regulating climate via storage and release of carbon. Anticipated changes in climate are expected to increase mortality and reduce biomass in many boreal tree species, putting at risk the functioning of this ecosystem and hence its role in carbon sequestration. Genomic offset methods leverage spatial distribution of genomic diversity and its association with environmental variables to predict population vulnerability to projected changes in climate. Here, we analyse over 60 populations and more than 1400 individuals of black spruce (Picea mariana (Mill.) B.S.P), a dominant boreal forest species, to compare population-level genomic offsets calculated using Gradient Forest and redundancy analysis (RDA) against multiple fitness traits measured in four long-term (>40 yr) common gardens. Within common gardens, we found that genomic offset predictions were largely unaffected by the model choice, the number or type of markers used for model training, with the strongest discrepancies observed for LFMM climate-associated markers. Model performance remained relatively stable when the number or size of populations in the training set was reduced, suggesting that these models can reliably project genomic offsets for new populations. However, model performances varied among common gardens, with highly accurate fitness predictions in some gardens but contradictory results in others. Model performance was influenced by the choice of climate predictors, their relationships with fitness traits, and the genetic cluster in which the models were evaluated. Overall, our results highlight the challenges of projecting genomic offsets across large spatial scales in genetically structured species, due to spatial variation in environmental drivers of adaptation and complex interactions among them. By capitalizing on our comprehensive validation, we identified the most robust models for projecting fitness declines in black spruce under future climate scenarios.

evolutionary biology↗

Corticosteroid resistance is predetermined by early immune response dynamics at acute Graft Versus Host disease onset

Steroid-resistant acute graft versus host disease (SR-aGVHD) is the leading life-threatening complication following allogeneic hematopoietic stem cell transplantation. Novel therapeutics development is impeded by scares knowledge on biological pathways leading to steroid resistance at time of aGVHD diagnosis. To gain insight into our understanding on circulating immune cell subsets and functions at time of aGVHD, a single cell deep phenotyping and transcriptome analysis was performed on peripheral blood mononuclear cells from patients with aGVHD before steroid treatment or without aGVHD. We aimed at identifying biological patterns associated with steroid resistance at early onset of aGVHD. First, circulating immune cell subsets were associated with increased incidence of aGVHD, but not with steroid sensitivity. Then, pathway analysis and inferred ligand/receptor interactions revealed major functional divergences between steroid-sensitive (SS-) and SR-aGVHD, including enrichment of TNF activation in SR-GVHD, as well as TNF/TNFR, CCL3, CCL4 and IL18 signaling, and decreased interferon and {gamma} signaling pathways, suggesting that steroid resistance in an intrinsic property of immune cells before any treatment. To go deeper into the understanding of mechanisms at play during SR-aGVHD, we modeled immune trajectories within CD8+ T cells and evidenced specific direct transition, from an early naive state to a highly activated one. By contrast, SS-aGVHD involved specific gene signatures across multiple intermediate differentiation stages during cell-to-cell transitions. These findings provide evidence that steroid resistance is driven by intrinsic mechanisms already present at the onset of alloimmune response, that may serve as potential new therapeutic targets.

molecular biology↗