Biology subjects

Gaillard, M.

Publications and source records attributed to Gaillard, M..

8 recordsLinked to original sources

bioRxiv2026

Routine FFPE sections support clinically compatible single-nucleus transcriptomics across six human cancer types

Tumor cellular composition--including malignant cell states, immune populations, and stromal populations--is increasingly recognized as a determinant of therapeutic response and resistance to anti-cancer agents, yet comprehensive cellular profiling remains largely confined to research settings. Here, we present a clinically compatible sample-to-report workflow for tumor composition profiling from routine formalin-fixed paraffin-embedded (FFPE) clinical specimens. By combining low-input single-nucleus RNA sequencing with foundation model- based automated cell annotation, this workflow enables prospective sample-by-sample analysis without dedicated research material or cohort-based processing. Across 116 clinical specimens representing six cancer types, we generated reproducible measurements of cellular composition and cell-type-specific gene expression, demonstrated high technical reproducibility, and showed concordance with pathological assessment of immune infiltration. The workflow was similarly applicable to archival FFPE material and ultra-low-input biopsy specimens. Together, these findings establish a practical framework for routine single-cell profiling from standard pathology specimens and open the perspective of prospective evaluation of cellular composition as a clinical biomarker in precision oncology.

cancer biology↗

bioRxiv2026

Evolution of multidrug-resistant IncC plasmids in the seventh pandemic Vibrio cholerae O1 El Tor lineage between 1979 and 2024

IncC plasmids played an important role in driving antimicrobial drug resistance development in the seventh pandemic Vibrio cholerae O1 El Tor (7PET) lineage during the 1970s and these have begun to re-emerge. In this study, we investigated a comprehensive dataset for 28 complete IncC plasmids -- including 17 newly sequenced plasmid genomes -- from 7PET isolates collected on various continents between 1979 and 2024 and distributed across the global phylogenetic tree for 7PET isolates. IncC type 2 predominated among the V. cholerae plasmids studied, and five new core genome sequence types (cgSTs) were identified. The antimicrobial resistance genes (ARGs) were arranged in islands inserted at specific hotspots within the common IncC backbone and were significantly associated with IncC types or islands. The IncC plasmid backbone has remained stable over the last 50 years, but the ARGs and their associated genomic islands displayed remarkable diversity, underscoring the complex evolution patterns of the 7PET lineage of V. cholerae and its considerable adaptability under selective pressure.

microbiology↗

bioRxiv2024

3D Reconstruction Enables High-Throughput Phenotyping and Quantitative Genetic Analysis of Phyllotaxy

Differences in canopy architecture play a role in determining both the light and water use efficiency. Canopy architecture is determined by several component traits, including leaf length, width, number, angle, and phyllotaxy. Phyllotaxy may be among the most difficult of the leaf canopy traits to measure accurately across large numbers of individual plants. As a result, in simulations of the leaf canopies of grain crops such as maize and sorghum, this trait is frequently approximated as alternating 180{degrees} angles between sequential leaves. We explore the feasibility of extracting direct measurements of the phyllotaxy of sequential leaves from 3D reconstructions of individual sorghum plants generated from 2D calibrated images and test the assumption of consistently alternating phyllotaxy across a diverse set of sorghum genotypes. Using a voxel-carving-based approach, we generate 3D reconstructions from multiple calibrated 2D images of 366 sorghum plants representing 236 sorghum genotypes from the sorghum association panel. The correlation between automated and manual measurements of phyllotaxy is only modestly lower than the correlation between manual measurements of phyllotaxy generated by two different individuals. Automated phyllotaxy measurements exhibited a repeatability of R2 = 0.41 across imaging timepoints separated by a period of two days. A resampling based genome wide association study (GWAS) identified several putative genetic associations with lower-canopy phyllotaxy in sorghum. This study demonstrates the potential of 3D reconstruction to enable both quantitative genetic investigation and breeding for phyllotaxy in sorghum and other grain crops with similar plant architectures.

plant biology↗

bioRxiv2023

Acyl-AcpB, a FabT co-repressor in Streptococcus pyogenes

Membranes are a universal barrier to all cells. Phospholipids, essential bacterial membrane components, are composed of a polar head and apolar fatty acid (FA) chains. Most bacterial FA are synthesized by the FA synthesis pathway (FASII). In streptococcaceae, enterococci and Lactococcus lactis, a unique feedback mechanism controls the FASII gene expression. FabT, encoded in the FASII main locus, is the repressor and it is activated by acyl-ACP. Many Streptococci, Enterococcus faecalis, but not L. lactis, possess two ACPS. AcpA encoding gene is within the FASII locus and is, to a certain extent, coregulated with the FASII genes. Acyl-AcpA is the end product of FASII. AcpB encoding gene is in operon with plsX. The role of AcpB as FabT corepressor is controversial. Streptococcus pyogenes, which causes a wide variety of diseases ranging from mild non-invasive to severe invasive infections, possesses AcpB. In this study, we show by comparing gene repression of FASII genes in wild-type, fabT mutant and acpB mutant strains grown in the presence and the absence of exogenous FAs, that AcpB is S. pyogenes FabT main co-repressor. Also, acpB deletion impacts the membrane FA composition and adhesion to eucaryotic cells, highlighting the role of AcpB.

microbiology↗

bioRxiv2023

The double-edged role of FASII regulator FabT in Streptococcus pyogenes infection

In Streptococcus pyogenes, the type II fatty acid (FA) synthesis pathway FASII is feedback- controlled by the FabT repressor bound to an acyl-Acyl carrier protein. Despite FabT defects being linked to reduced virulence in animal models, spontaneous fabT mutants arise in vivo. To resolve this paradox, we characterized the conditions and mechanisms that require FabT activity, and those that promote fabT mutant emergence. The primary fabT mutant defect is energy dissipation: specific nutrients are consumed, but the mutant fails to grow on human tissue, cells, or cell filtrates where nutrients are limited. These features explain the FabT requirement during infection. Conversely, fabT mutants exhibited a marked growth advantage over the wild-type in biotopes rich in saturated FAs. fabT mutants emerge in this context, where continued FASII activity prevented environmental FA incorporation. An ex vivo muscle model demonstrated that wild-type S. pyogenes was inhibited, while fabT mutant growth was stimulated, but conditional to FASII activity. Our findings elucidate the rationale for emerging fabT mutants that improve survival in lipid-rich biotopes, but lead to a genetic impasse for infection.

microbiology↗

bioRxiv2021

3D reconstruction identifies loci linked to variation in angle of individual sorghum leaves

Selection for yield at high planting density has reshaped the leaf canopy of maize, improving photosynthetic productivity in high density settings. Further optimization of canopy architecture may be possible. However, measuring leaf angles, the widely studied component trait of leaf canopy architecture, by hand is a labor and time intensive process. Here, we use multiple, calibrated, 2D images to reconstruct the 3D geometry of individual sorghum plants using a voxel carving based algorithm. Automatic skeletonization and segmentation of these 3D geometries enable quantification of the angle of each leaf for each plant. The resulting measurements are both heritable and correlated with manually collected leaf angles. This automated and scaleable reconstruction approach was employed to measure leaf-by-leaf angles for a population of 366 sorghum plants at multiple time points, resulting in 971 successful reconstructions and 3,376 leaf angle measurements from individual leaves. A genome wide association study conducted using aggregated leaf angle data identified a known large effect leaf angle gene, several previously identified leaf angle QTL from a sorghum NAM population, and novel signals. Genome wide association studies conducted separately for three individual sorghum leaves identified a number of the same signals, a previously unreported signal shared across multiple leaves, and signals near the sorghum orthologs of two maize genes known to influence leaf angle. Automated measurement of individual leaves and mapping variants associated with leaf angle reduce the barriers to engineering ideal canopy architectures in sorghum and other grain crops.

plant biology↗

bioRxiv2021

Hematopoietic differentiation is characterized by a transient peak of cell-to-cell gene expression variability in normal and pathological conditions.

Hematopoietic differentiation has been metaphorically represented as linear trajectories with discrete steps from hematopoietic stem cells to mature cells. While the transcriptional state of cells at the beginning or at the end of these trajectories are well described from bulk analysis, what happens in the intermediate states has remained elusive until the use of single cell approaches. Applying Shannon entropy to measure cell-to-cell variability among cells at the same stage of differentiation, we observed a transient peak of gene expression variability in all the hematopoietic differentiation pathways. Strikingly, genes with the highest entropy variation in a given differentiation pathway matched genes known as pathway-specific, whereas genes with the highest expression variation were common to all pathways. Finally, we showed that the level of cell-to-cell variation is increased in the most immature compartment of hematopoiesis in myelodysplastic syndromes. These data suggest that differentiation could be better conceptualized as a dynamical stochastic process with a transient stage of cellular indetermination.

cell biology↗

bioRxiv2020

Voxel Carving Based 3D Reconstruction of Sorghum Identifies Genetic Determinants of Radiation Interception Efficiency

Changes in canopy architecture traits have been shown to contribute to yield increases. Optimizing both light interception and radiation use efficiency of agricultural crop canopies will be essential to meeting growing needs for food. Canopy architecture is inherently 3D, but many approaches to measuring canopy architecture component traits treat the canopy as a two dimensional structure in order to make large scale measurement, selective breeding, and gene identification logistically feasible. We develop a high throughput voxel carving strategy to reconstruct three dimensional representations of maize and sorghum from a small number of RGB photos. This approach was employed to generate three dimensional reconstructions of a sorghum association population at the late vegetative stage of development. Light interception parameters estimated from these reconstructions enabled the identification of both known and previously unreported loci controlling light interception efficiency in sorghum. The approach described here is generalizable and scalable and it enables 3D reconstructions from existing plant high throughput phenotyping datasets. For future datasets we propose a set of best practices to increase the accuracy of three dimensional reconstructions.

plant biology↗