Publications by authors named "Etienne Patin"

Infections have imposed strong selection pressures throughout human evolution, making the study of natural selection's effects on immunity genes highly complementary to disease-focused research. This review discusses how ancient DNA studies, which have revolutionized evolutionary genetics, increase our understanding of the evolution of human immunity. These studies have shown that interbreeding between modern humans and Neanderthals or Denisovans has influenced present-day immune responses, particularly to viruses.

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Microbial pathogenesis is mediated by the expression of virulence genes. However, as microbes with identical virulence gene content can differ in their pathogenic potential, other virulence determinants must be involved. Here, by combining comparative genomics and transcriptomics of a large collection of isolates of the model pathogen Listeria monocytogenes, time-lapse microscopy, in vitro evolution and in vivo experiments, we show that the individual stress responsiveness of L.

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Human admixture history is rarely a simple process in which distinct populations, previously isolated for a long time, come into contact once to form an admixed population. In this study, we aim to reconstruct the complex admixture histories of the population of São Tomé, an island in the Gulf of Guinea that was the site of the first slave-based plantation economy, and experienced successive waves of forced and deliberate migration from Africa. We examined 2.

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Aging is associated with genome-wide changes in DNA methylation in humans, facilitating the development of epigenetic age prediction models. However, most of these models have been trained primarily on European-ancestry individuals, and none account for the impact of methylation quantitative trait loci (meQTL). To address these gaps, we analyzed the relationships between age, genotype, and CpG methylation in 3 understudied populations: central African Baka (n = 35), southern African ‡Khomani San (n = 52), and southern African Himba (n = 51).

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Leveraging past allele frequencies has proven to be key for identifying the impact of natural selection across time. However, this approach suffers from imprecise estimations of the intensity (s) and timing (T) of selection, particularly when ancient samples are scarce in specific epochs. Here, we aimed to bypass the computation of allele frequencies across arbitrarily defined past epochs and refine the estimations of selection parameters by implementing convolutional neural networks (CNNs) algorithms that directly use ancient genotypes sampled across time.

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Multivariate analysis is becoming central in studies investigating high-throughput molecular data, yet, some important features of these data are seldom explored. Here, we present MANOCCA (Multivariate Analysis of Conditional CovAriance), a powerful method to test for the effect of a predictor on the covariance matrix of a multivariate outcome. The proposed test is by construction orthogonal to tests based on the mean and variance and is able to capture effects that are missed by both approaches.

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Background: French Polynesia is a French overseas collectivity in the Southeast Pacific, comprising 75 inhabited islands across five archipelagoes. The human settlement of the region corresponds to the last massive migration of humans to empty territories, but its timeline is still debated. Despite their recent population history and geographical isolation, inhabitants of French Polynesia experience health issues similar to those of continental countries.

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Individuals differ widely in their immune responses, with age, sex and genetic factors having major roles in this inherent variability. However, the variables that drive such differences in cytokine secretion-a crucial component of the host response to immune challenges-remain poorly defined. Here we investigated 136 variables and identified smoking, cytomegalovirus latent infection and body mass index as major contributors to variability in cytokine response, with effects of comparable magnitudes with age, sex and genetics.

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Purpose: We aimed to describe the clinical, immunological, and genetic features of patients with DOCK8 deficiency (DOCK8-Def) in a tertiary care center for children.

Methods: Retrospective chart review of patients' clinical, immunological, and genetic characteristics with DOCK8-Def. Genetic analysis was performed with targeted- or whole-exome sequencing; we also assessed DOCK8 protein expression and a lymphoproliferation assay and analyzed survival by the Kaplan-Meier method.

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Article Synopsis
  • A commensal yeast commonly found in the gut of healthy individuals varies in concentration, and this study examines how factors like microbiota, lifestyle, and genetics affect these levels among 695 participants.
  • The research found that 82.9% of subjects carried the yeast, with a negative correlation observed between its levels and a specific gut microbiota species, and diet choices like eating between meals and having a low-sodium diet promoting higher levels of the yeast.
  • Additionally, the study identified 26 genetic variations linked to yeast colonization and suggested that yeast levels may influence the immune response, with positive correlations found between yeast concentration and certain immune gene expressions and cytokine levels.
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Humans display substantial interindividual clinical variability after SARS-CoV-2 infection, the genetic and immunological basis of which has begun to be deciphered. However, the extent and drivers of population differences in immune responses to SARS-CoV-2 remain unclear. Here we report single-cell RNA-sequencing data for peripheral blood mononuclear cells-from 222 healthy donors of diverse ancestries-that were stimulated with SARS-CoV-2 or influenza A virus.

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Article Synopsis
  • Ancient genomics can reveal how humans have adapted genetically to environmental changes and pathogens over the last 10,000 years.
  • Using a sophisticated statistical method, researchers analyzed 2,879 genomes to understand the historical selection pressures on human genetics.
  • Significant genetic adaptations mainly occurred after the Bronze Age, affecting immune-related genes, and the findings indicate that the risk of inflammatory diseases may have increased in Europeans since the Neolithic period due to these adaptations.
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Epigenetic changes are required for normal development, yet the nature and respective contribution of factors that drive epigenetic variation in humans remain to be fully characterized. Here, we assessed how the blood DNA methylome of 884 adults is affected by DNA sequence variation, age, sex and 139 factors relating to life habits and immunity. Furthermore, we investigated whether these effects are mediated or not by changes in cellular composition, measured by deep immunophenotyping.

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The Vanuatu archipelago served as a gateway to Remote Oceania during one of the most extensive human migrations to uninhabited lands ∼3,000 years ago. Ancient DNA studies suggest an initial settlement by East Asian-related peoples that was quickly followed by the arrival of Papuan-related populations, leading to a major population turnover. Yet there is uncertainty over the population processes and the sociocultural factors that have shaped the genomic diversity of ni-Vanuatu, who present nowadays among the world's highest linguistic and cultural diversity.

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Article Synopsis
  • The IL-12 family consists of unique cytokines that have various functional roles and the study found a dual response of IL-12p70 to LPS stimulation in healthy individuals.
  • Interferon β (IFNβ) plays a crucial role in promoting IL-12p70 production, and this effect is linked to the levels and activation of circulating monocytes.
  • The findings are clinically relevant, showing that patients with severe SARS-CoV-2 or chronic hepatitis C infections exhibit diminished IFNβ-IL-12p70 responses, which improve once the viral infection is resolved.
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It is commonly thought that the spread of agriculture and farmers led to the decline of hunter-gatherer populations. A new study found that the demographic responses of Ethiopian foragers to this major cultural transition have been more diverse than anticipated.

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Background: Blood plasma proteins play an important role in immune defense against pathogens, including cytokine signaling, the complement system, and the acute-phase response. Recent large-scale studies have reported genetic (i.e.

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Admixture has been a pervasive phenomenon in human history, extensively shaping the patterns of population genetic diversity. There is increasing evidence to suggest that admixture can also facilitate genetic adaptation to local environments, i.e.

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During their dispersals over the last 100,000 years, modern humans have been exposed to a large variety of environments, resulting in genetic adaptation. While genome-wide scans for the footprints of positive Darwinian selection have increased knowledge of genes and functions potentially involved in human local adaptation, they have globally produced evidence of a limited contribution of selective sweeps in humans. Conversely, studies based on machine learning algorithms suggest that recent sweeps from standing variation are widespread in humans, an observation that has been recently questioned.

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Population genetic studies have clearly indicated that immunity and host defense are among the functions most frequently subject to natural selection, and increased our understanding of the biological relevance of the corresponding genes and their contribution to variable immune traits and diseases. Herein, we will focus on some recently studied forms of human adaptation to infectious agents, including hybridization with now-extinct hominins, such as Neanderthals and Denisovans, and admixture between modern human populations. These studies, which are partly enabled by the technological advances in the sequencing of DNA from ancient remains, provide new insight into the sources of immune response variation in contemporary humans, such as the recently reported link between Neanderthal heritage and susceptibility to severe COVID-19 disease.

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The Pacific region is of major importance for addressing questions regarding human dispersals, interactions with archaic hominins and natural selection processes. However, the demographic and adaptive history of Oceanian populations remains largely uncharacterized. Here we report high-coverage genomes of 317 individuals from 20 populations from the Pacific region.

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Tuberculosis (TB), usually caused by Mycobacterium tuberculosis bacteria, is the first cause of death from an infectious disease at the worldwide scale, yet the mode and tempo of TB pressure on humans remain unknown. The recent discovery that homozygotes for the P1104A polymorphism of TYK2 are at higher risk to develop clinical forms of TB provided the first evidence of a common, monogenic predisposition to TB, offering a unique opportunity to inform on human co-evolution with a deadly pathogen. Here, we investigate the history of human exposure to TB by determining the evolutionary trajectory of the TYK2 P1104A variant in Europe, where TB is considered to be the deadliest documented infectious disease.

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Genetic variants underlying life-threatening diseases, being unlikely to be transmitted to the next generation, are gradually and selectively eliminated from the population through negative selection. We study the determinants of this evolutionary process in human genes underlying monogenic diseases by comparing various negative selection scores and an integrative approach, CoNeS, at 366 loci underlying inborn errors of immunity (IEI). We find that genes underlying autosomal dominant (AD) or X-linked IEI have stronger negative selection scores than those underlying autosomal recessive (AR) IEI, whose scores are not different from those of genes not known to be disease causing.

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Host-microbial co-metabolism products are being increasingly recognised to play important roles in physiological processes. However, studies undertaking a comprehensive approach to consider host-microbial metabolic relationships remain scarce. Metabolomic analysis yielding detailed information regarding metabolites found in a given biological compartment holds promise for such an approach.

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Article Synopsis
  • Microbial therapeutics are being studied in various patient groups, necessitating an understanding of factors affecting the microbiome, such as host characteristics and lifestyle choices.
  • An analysis of gut microbiome samples from healthy individuals revealed that biological sex was the most significant influence on microbiome composition, with notable changes in bacteria types linked to aging.
  • The findings indicate that variations in the microbiome are predictable based on sex, age, and health status, which is crucial for developing effective microbiome-targeted therapies and interpreting related health outcomes.
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