Since the first genome-wide association studies (GWASs), thousands of variant-trait associations have been discovered. However, comprehensively mapping the genetic determinant of complex traits through univariate testing can require prohibitive sample sizes. Multi-trait GWAS can circumvent this issue and improve statistical power by leveraging the joint genetic architecture of human phenotypes.
View Article and Find Full Text PDFBackground: As a single reference genome cannot possibly represent all the variation present across human individuals, pangenome graphs have been introduced to incorporate population diversity within a wide range of genomic analyses. Several data structures have been proposed for representing collections of genomes as pangenomes, in particular graphs.
Results: In this work, we collect all publicly available high-quality human haplotypes and construct the largest human pangenome graphs to date, incorporating 52 individuals in addition to two synthetic references (CHM13 and GRCh38).
Since the first Genome-Wide Association Studies (GWAS), thousands of variant-trait associations have been discovered. However, the sample size required to detect additional variants using standard univariate association screening is increasingly prohibitive. Multi-trait GWAS offers a relevant alternative: it can improve statistical power and lead to new insights about gene function and the joint genetic architecture of human phenotypes.
View Article and Find Full Text PDFBackground: Climate change and globalization contribute to the expansion of mosquito vectors and their associated pathogens. Long spared, temperate regions have had to deal with the emergence of arboviruses traditionally confined to tropical regions. Chikungunya virus (CHIKV) was reported for the first time in Europe in 2007, causing a localized outbreak in Italy, which then recurred repeatedly over the years in other European localities.
View Article and Find Full Text PDFThe genus includes a large variety of nonpathogenic and life-threatening pathogenic bacteria, which cause a broad spectrum of diseases in humans and animals, such as plague, enteritis, Far East scarlet-like fever (FESLF), and enteric redmouth disease. Like most clinically relevant microorganisms, spp. are currently subjected to intense multi-omics investigations whose numbers have increased extensively in recent years, generating massive amounts of data useful for diagnostic and therapeutic developments.
View Article and Find Full Text PDFBackground: Comparing the composition of microbial communities among groups of interest (e.g., patients vs healthy individuals) is a central aspect in microbiome research.
View Article and Find Full Text PDFProtozoan parasites of the genus adapt to environmental change through chromosome and gene copy number variations. Only little is known about external or intrinsic factors that govern genomic adaptation. Here, by conducting longitudinal genome analyses of 10 new clinical isolates, we uncovered important differences in gene copy number among genetically highly related strains and revealed gain and loss of gene copies as potential drivers of long-term environmental adaptation in the field.
View Article and Find Full Text PDFLeptospira is a phylogenetically unique group of bacteria, and includes the causative agents of leptospirosis, the most globally prevalent zoonosis. Bacteriophages in Leptospira are largely unexplored. To date, a genomic sequence is available for only one temperate leptophage called LE1.
View Article and Find Full Text PDFLeptospirosis is a widespread zoonosis, potentially severe in humans, caused by spirochetal bacteria, Leptospira interrogans (L. interrogans). Host defense mechanisms involved in leptospirosis are poorly understood.
View Article and Find Full Text PDFAs for many model organisms, the amount of omics data produced has recently increased exponentially. There are now >80 published complete genomes, around 350 different transcriptomic data sets, and 25 proteomic data sets available. The analysis of these data sets through a systems biology approach and the generation of tools for biologists to browse these various data are a challenge for bioinformaticians.
View Article and Find Full Text PDFLegionella pneumophila is an environmental bacterium and the leading cause of Legionnaires' disease. Just five sequence types (ST), from more than 2000 currently described, cause nearly half of disease cases in northwest Europe. Here, we report the sequence and analyses of 364 L.
View Article and Find Full Text PDFThe biological impact of alternative splicing is poorly understood in fungi, although recent studies have shown that these microorganisms are usually intron-rich. In this study, we re-annotated the genome of C. neoformans var.
View Article and Find Full Text PDFAll eukaryotic genomes encode multiple members of the heat shock protein 70 (HSP70) family, which evolved distinctive structural and functional features in response to specific environmental constraints. Phylogenetic analysis of this protein family thus can inform on genetic and molecular mechanisms that drive species-specific environmental adaptation. Here we use the eukaryotic pathogen Leishmania spp.
View Article and Find Full Text PDFThe rare patients who are able to spontaneously control HIV replication in the absence of therapy show signs of a particularly efficient cellular immune response. To identify the molecular determinants that underlie this response, we characterized the T cell receptor (TCR) repertoire directed at Gag293, the most immunoprevalent CD4 epitope in the HIV-1 capsid. HIV controllers from the ANRS CODEX cohort showed a highly skewed TCR repertoire that was characterized by a predominance of TRAV24 and TRBV2 variable genes, shared CDR3 motifs, and a high frequency of public clonotypes.
View Article and Find Full Text PDFStreptococcus agalactiae (Group B Streptococcus, GBS) is a commensal of the digestive and genitourinary tracts of humans that emerged as the leading cause of bacterial neonatal infections in Europe and North America during the 1960s. Due to the lack of epidemiological and genomic data, the reasons for this emergence are unknown. Here we show by comparative genome analysis and phylogenetic reconstruction of 229 isolates that the rise of human GBS infections corresponds to the selection and worldwide dissemination of only a few clones.
View Article and Find Full Text PDFFor nearly 3 decades, listeriologists and immunologists have used mainly three strains of the same serovar (1/2a) to analyze the virulence of the bacterial pathogen Listeria monocytogenes. The genomes of two of these strains, EGD-e and 10403S, were released in 2001 and 2008, respectively. Here we report the genome sequence of the third reference strain, EGD, and extensive genomic and phenotypic comparisons of the three strains.
View Article and Find Full Text PDFUnlabelled: The intestinal tract is the largest reservoir of microbes in the human body. The intestinal microbiota is thought to be able to modulate alterations of the gut induced by enteropathogens, thereby maintaining homeostasis. Listeria monocytogenes is the agent of listeriosis, an infection transmitted to humans upon ingestion of contaminated food.
View Article and Find Full Text PDFBMC Bioinformatics
September 2013
Background: Dynamic visualisation interfaces are required to explore the multiple microbial genome data now available, especially those obtained by high-throughput sequencing - a.k.a.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2012
Listeria monocytogenes is a foodborne pathogen that crosses the intestinal barrier and disseminates within the host. Here, we report a unique comprehensive analysis of the impact of two Lactobacillus species, Lactobacillus paracasei CNCM I-3689 and Lactobacillus casei BL23, on L. monocytogenes and orally acquired listeriosis in a gnotobiotic humanized mouse model.
View Article and Find Full Text PDFCandidaDB (http://genodb.pasteur.fr/CandidaDB) was established in 2002 to provide the first genomic database for the human fungal pathogen Candida albicans.
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