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Gautreau, G.

Publications and source records attributed to Gautreau, G..

5 recordsLinked to original sources

PanGBank: a large-scale resource of precomputed microbial pangenomes built with PPanGGOLiN

PanGBank (https://pangbank.genoscope.cns.fr) is a comprehensive open-access database providing precomputed prokaryotic pangenomes at a broad taxonomic scale. Built upon PPanGGOLiN partitioned pangenome graphs, PanGBank addresses the growing need for large-scale comparative genomics through a standardized, regularly updated, and fully accessible resource. The initial release comprises two complementary collections covering more than 4,600 prokaryotic species from the Genome Taxonomy Database (GTDB), encompassing over 393,000 genomes: GTDB all, maximizing taxonomic and environmental diversity through the inclusion of MAGs and SAGs, and GTDB refseq, focusing on high-quality, annotation-rich genomes. Each species-level pangenome integrates graph-based statistical partitions into persistent, shell, and cloud gene families, together with regions of genomic plasticity (panRGP) and co-localized functional modules (panModule). PanGBank offers multiple access modes, including a REST API, a command-line interface (PanGBank-cli), and an interactive web interface. By combining large-scale pangenome resources with advanced graph-based analyses, PanGBank provides a scalable framework for exploring microbial diversity, genome evolution, functional variation, and the dissemination of adaptive traits across prokaryotic populations, as illustrated by a use case on Acinetobacter baumannii pangenome investigating the distribution and evolution of antimicrobial resistance determinants. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=63 SRC="FIGDIR/small/742796v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@12c441org.highwire.dtl.DTLVardef@12b079org.highwire.dtl.DTLVardef@ffd7f8org.highwire.dtl.DTLVardef@bc013f_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

CDKN1A (p21Cip/Waf1) stabilizes Cyclin D3 by inhibiting its phosphorylation-dependent nuclear export following butyrate treatment

Butyrate-mediated inhibition of cell proliferation is part of the preventive role of dietary fiber against colorectal cancer (CRC). This effect notably involves the cyclin-dependent kinase inhibitor CDKN1A (p21Cip/Waf1) in human intestinal cells, yet the underlying molecular mechanisms remain incompletely understood. Previously, we observed a paradoxical increase in cyclin D3 (CCND3)--but not cyclin D1--levels upon butyrate exposure. Here, we demonstrate that the butyrate-induced accumulation of CCND3 protein results both from mRNA increase and a CDKN1A-dependent protein stabilization, specifically extending its nuclear half-life. Proteomic analyses of CCND3 co-immunoprecipitates identified complexes involving CDKN1A, CDK4, CDK6, and the CRC-associated kinase CDK5, particularly enriched in butyrate-treated cells. Phosphorylation at a conserved Thr residue, crucial for CCND nuclear export and subsequent proteasomal degradation, was notably reduced following butyrate treatment and inversely correlated with CDKN1A expression levels. Structural modeling based on AlphaFold2, complemented by molecular dynamics simulations, revealed possible differential interactions between CDKN1A and cyclins D1 and D3, predicting that CCND3-Thr283 becomes structurally buried upon CDKN1A binding, limiting its phosphorylation. Our findings provide novel mechanistic insights into how CDKN1A might regulate CCND3 stability, highlighting previously unexplored roles of cyclin D3-containing complexes in cell cycle arrest induced by butyrate.

cell biology↗

CroCoDeEL: accurate control-free detection of cross-sample contamination in metagenomic data

Metagenomic sequencing provides profound insights into microbial communities, but it is often compromised by technical biases, including cross-sample contamination. This phenomenon arises when microbial content is inadvertently exchanged among concurrently processed samples, distorting microbial profiles and compromising the reliability of metagenomic data and downstream analyses. Existing detection methods often rely on negative controls, which are inconvenient and do not detect contamination within real samples. Meanwhile, strain-level bioinformatics approaches fail to distinguish contamination from natural strain sharing and lack sensitivity. To fill this gap, we introduce CroCoDeEL, a decision-support tool for detecting and quantifying cross-sample contamination. Leveraging linear modeling and a pre-trained supervised model, CroCoDeEL identifies specific contamination patterns in species abundance profiles. It requires no negative controls or prior knowledge of sample processing positions, offering improved accuracy and versatility. Benchmarks across three public datasets demonstrate that CroCoDeEL accurately detects contaminated samples and identifies their contamination sources, even at low rates (<0.1%), provided sufficient sequencing depth. Notably, we discovered critical contamination cases in highly cited studies, calling some of their results into question. Our findings suggest that cross-sample contamination is a widespread yet underexplored issue in metagenomics and emphasize the necessity of systematically integrating contamination detection into sequencing quality control.

bioinformatics↗

panRGP: a pangenome-based method to predict genomic islands and explore their diversity

MotivationHorizontal gene transfer (HGT) is a major source of variability in prokaryotic genomes. Regions of Genome Plasticity (RGPs) are clusters of genes located in highly variable genomic regions. Most of them arise from HGT and correspond to Genomic Islands (GIs). The study of those regions at the species level has become increasingly difficult with the data deluge of genomes. To date no methods are available to identify GIs using hundreds of genomes to explore their diversity. ResultsWe present here the panRGP method that predicts RGPs using pangenome graphs made of all available genomes for a given species. It allows the study of thousands of genomes in order to access the diversity of RGPs and to predict spots of insertions. It gave the best predictions when benchmarked along other GI detection tools against a reference dataset. In addition, we illustrated its use on Metagenome Assembled Genomes (MAGs) by redefining the borders of the leuX tRNA hotspot, a well studied spot of insertion in Escherichia coli. panRPG is a scalable and reliable tool to predict GIs and spots making it an ideal approach for large comparative studies. AvailabilityThe methods presented in the current work are available through the following software: https://github.com/labgem/PPanGGOLiN. Detailed results and scripts to compute the benchmark metrics are available at https://github.com/axbazin/panrgp_supdata. Contactvallenet@genoscope.cns.fr and acalteau@genoscope.cns.fr Supplementary informationNone.

bioinformatics↗

PPanGGOLiN: Depicting microbial diversity via a Partitioned Pangenome Graph

The use of comparative genomics for functional, evolutionary, and epidemiological studies requires methods to classify gene families in terms of occurrence in a given species. These methods usually lack multivariate statistical models to infer the partitions and the optimal number of classes and dont account for genome organization. We introduce a graph structure to model pangenomes in which nodes represent gene families and edges represent genomic neighborhood. Our method, named PPanGGOLiN, partitions nodes using an Expectation-Maximization algorithm based on multivariate Bernoulli Mixture Model coupled with a Markov Random Field. This approach takes into account the topology of the graph and the presence/absence of genes in pangenomes to classify gene families into persistent, cloud, and one or several shell partitions. By analyzing the partitioned pangenome graphs of isolate genomes from 439 species and metagenome-assembled genomes from 78 species, we demonstrate that our method is effective in estimating the persistent genome. Interestingly, it shows that the shell genome is a key element to understand genome dynamics, presumably because it reflects how genes present at intermediate frequencies drive adaptation of species, and its proportion in genomes is independent of genome size. The graph-based approach proposed by PPanGGOLiN is useful to depict the overall genomic diversity of thousands of strains in a compact structure and provides an effective basis for very large scale comparative genomics. The software is freely available at https://github.com/labgem/PPanGGOLiN. Author summaryMicroorganisms have the greatest biodiversity and evolutionary history on earth. At the genomic level, it is reflected by a highly variable gene content even among organisms from the same species which explains the ability of microbes to be pathogenic or to grow in specific environments. We developed a new method called PPanGGOLiN which accurately represent the genomic diversity of a species (i.e. its pangenome) using a compact graph structure. Based on this pangenome graph, we classify genes by a statistical method according to their occurrence in the genomes. This method allowed us to build pangenomes even for uncultivated species at an unprecedented scale. We applied our method on all available genomes in databanks in order to depict the overall diversity of hundreds of species. Overall, our work enables microbiologists to explore and visualize pangenomes alike a subway map.

bioinformatics↗