Biology subjects

Dupont, C.

Publications and source records attributed to Dupont, C..

5 recordsLinked to original sources

bioRxiv2018

Supragingival plaque microbiome ecology and functional potential in the context of health and disease

To address the question of how microbial diversity and function in the oral cavities of children relates to caries diagnosis, we surveyed the supragingival plaque biofilm microbiome in 44 juvenile twin pairs. Using shotgun sequencing, we constructed a genome encyclopedia describing the core supragingival plaque microbiome. Caries phenotypes contained statistically significant enrichments in specific genome abundances and distinct community composition profiles including strain-level changes. Metabolic pathways that are statistically associated with caries include several sugar-associated phosphotransferase systems, antimicrobial resistance, and metal transport. Numerous closely-related previously-uncharacterized microbes had substantial variation in central metabolism, including the loss of biosynthetic pathways resulting in auxotrophy, changing the ecological role. We also describe the first complete Gracilibacteria genomes from the human microbiome. Caries is a microbial community metabolic disorder that cannot be described by a single etiology and our results provide the information needed for next generation diagnostic tools and therapeutics for caries.

microbiology↗

bioRxiv2018

Microbiome disturbance and resilience dynamics of the upper respiratory tract in response to influenza A virus infection in analog hosts

Infection with influenza can be aggravated by bacterial co-infections, which often results in disease exacerbation because of host responses and cellular damage. The native upper respiratory tract (URT) microbiome likely plays a role, yet the effects of influenza infection on the URT microbiome are largely unknown. We performed a longitudinal study to assess the temporal dynamics of the URT microbiomes of uninfected and influenza virus-infected humans and ferrets. Uninfected human patients and ferret URT microbiomes had stable \"heathy ecostate\" communities both within and between individuals. In contrast, infected patients and ferrets exhibited large changes in bacterial community composition over time and between individuals. The \"unhealthy\" ecostates of infected individuals progressed towards the \"healthy ecostate\" over time, coinciding with viral clearance and recovery. Blooms of Pseudomonas were a statistically associated constant in the disturbed microbiomes of infected individuals. The dynamic and resilient nature of the microbiome during influenza virus infection in multiple hosts provides a compelling rationale for the maintenance of the microbiome homeostasis as a potential therapeutic target to prevent IAV associated bacterial co-infections.\n\nOne Sentence SummaryDynamics of the upper respiratory tract microbiome during influenza A virus infection

microbiology↗

bioRxiv2017

Allele-specific control of replication timing and genome organization during development

DNA replication occurs in a defined temporal order known as the replication-timing (RT) program. RT is regulated during development in discrete chromosomal units, coordinated with transcriptional activity and 3D genome organization. Here, we derived distinct cell types from F1 hybrid musculus X castaneus mouse crosses and exploited the high single nucleotide polymorphism (SNP) density to characterize allelic differences in RT (Repli-seq), genome organization (Hi-C and promoter-capture Hi-C), gene expression (nuclear RNA-seq) and chromatin accessibility (ATAC-seq). We also present HARP: a new computational tool for sorting SNPs in phased genomes to efficiently measure allele-specific genome-wide data. Analysis of 6 different hybrid mESC clones with different genomes (C57BL/6, 129/sv and CAST/Ei), parental configurations and gender revealed significant RT asynchrony between alleles across ~12 % of the autosomal genome linked to sub-species genomes but not to parental origin, growth conditions or gender. RT asynchrony in mESCs strongly correlated with changes in Hi-C compartments between alleles but not SNP density, gene expression, imprinting or chromatin accessibility. We then tracked mESC RT asynchronous regions during development by analyzing differentiated cell types including extraembryonic endoderm stem (XEN) cells, 4 male and female primary mouse embryonic fibroblasts (MEFs) and neural precursors (NPCs) differentiated in vitro from mESCs with opposite parental configurations. Surprisingly, we found that RT asynchrony and allelic discordance in Hi-C compartments seen in mESCs was largely lost in all differentiated cell types, coordinated with a more uniform Hi-C compartment arrangement, suggesting that genome organization of homologues converges to similar folding patterns during cell fate commitment.

cell biology↗

bioRxiv2017

Correlated expression of archaeal ammonia oxidation machinery across disparate environmental and culture conditions

Thaumarchaea are ubiquitous in marine habitats where they participate in carbon and nitrogen cycling. Although metatranscriptomes suggest thaumarchaea are active microbes in marine waters, we understand little about how thaumarchaeal gene expression patterns relate to substrate utilization and activity. Here, we report the global transcriptional response of the marine ammonia-oxidizing thaumarchaeon Candidatus Nitrosopelagicus brevis str. CN25 to ammonia limitation using RNA-Seq. We further describe the genome and transcriptome of Ca. N. brevis str. U25, a new strain capable of urea utilization. Ammonia limitation in CN25 resulted in reduced expression of transcripts coding for ammonia oxidation proteins, and increased expression of a gene coding an Hsp20-like chaperone. Despite significantly different transcript abundances across treatments, two ammonia monooxygenase subunits (amoAB), a nitrite reductase (nirK), and both ammonium transporter genes were always among the most abundant transcripts, regardless of growth state. Ca. N. brevis str. U25 cells expressed a urea transporter 139-fold more than the urease catalytic subunit ureC. Gene co-expression networks derived from culture transcriptomes and ten thaumarchaea-enriched metatranscriptomes revealed a high degree of correlated gene expression across disparate environmental conditions and identified a module of genes, including amoABC and nirK, that we hypothesize to represent the core ammonia oxidation machinery.\n\nOriginality-Significance StatementDiscovering gene function in fastidious or uncultivated lineages remains one of the biggest challenges in environmental microbiology. Here, we use an approach that combines controlled laboratory experiments with in situ transcript abundance data from the environment to identify genes that share similar transcription patterns in marine ammonia-oxidizing thaumarchaea. These findings demonstrate how transcriptomes from microbial cultures can be used together with complex environmental samples to identify suites of co-expressed genes that are otherwise enigmatic and provide new insights into the mechanism of ammonia oxidation. Our results add to the growing body of literature showing that relatively small changes in transcript abundance are linked to large changes in growth in organisms with reduced genomes, suggesting they have limited capacity for metabolic regulation or that they rely on mechanisms other than transcriptional regulation to deal with a fluctuating environment.

microbiology↗

bioRxiv2017

A framework to identify modifier genes in patients with Phelan-McDermid syndrome

Phelan-McDermid syndrome (PMS) is characterized by a variety of clinical symptoms with heterogeneous degrees of severity, including intellectual disability, speech impairment, and autism spectrum disorders (ASD). It results from a deletion of the 22q13 locus that in most cases includes the SHANK3 gene. SHANK3 is considered a major gene for PMS, but the factors modulating the severity of the syndrome remain largely unknown. In this study, we investigated 85 PMS patients with different 22q13 rearrangements (78 deletions, 7 duplications). We first explored their clinical features and provide evidence for frequent corpus callosum abnormalities. We then mapped candidate genomic regions at the 22q13 locus associated with risk of clinical features, and suggest a second locus associated with absence of speech. Finally, in some cases, we identified additional rearrangements at loci associated with ASD, potentially modulating the severity of the syndrome. We also report the first SHANK3 deletion transmitted to five affected daughters by a mother without intellectual disability nor ASD, suggesting that some individuals could compensate for such mutations. In summary, we shed light on the genotype-phenotype relationship of PMS, a step towards the identification of compensatory mechanisms for a better prognosis and possibly treatments of patients with neurodevelopmental disorders.

genetics↗