Full-genome next-generation sequencing of hepatitis C virus to assess the accuracy of genotyping by the commercial assay LiPA and the prevalence of resistance-associated substitutions in a Belgian cohort

Funding Information: This work and KTC were supported by grants from the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO) ( G069214 , G0B2317N , 1S38819N ). LC acknowledges FWO travel grant for a research visit at University of Oxford ( V431117N ). The authors thank the staff in Oxford in their support of the laboratory work and the donation of the probes used for enrichment of HCV. Publisher Copyright: © 2022 Elsevier B.V.Background: Although most currently used regimens for Hepatitis C virus (HCV) infections can be initiated without prior knowledge of genotype and subtype, genotyping is still useful to identify patients who might benefit from a personalized treatment due to resistance to direct-acting antivirals (DAA). Objectives: To assess the utility of full-genome next-generation sequencing (FG-NGS) for HCV genotyping. Study design: 138 HCV plasma samples previously genotyped by VERSANT HCV Genotype Assay (LiPA) were subjected to FG-NGS and phylogenetically genotyped Genome Detective. Consensuses were analysed by HCV-GLUE for resistance-associated substitutions (RASs) and their impact on treatment response was investigated. Results: 102/138 (73.9%) samples were sequenced to a genome coverage and depth of >90% of the HCV open reading frame covered by >100 reads/site. Concordant genotype and subtype results were assigned in 97.1% and 79.4% of samples, respectively. FG-NGS resolved the subtype of 13.7% samples that had ambiguous calls by LiPA and identified one dual infection and one recombinant strain. At least one RAS was found for the HCV genes NS3, NS5A, and NS5B in 2.91%, 36.98% and 27.3% samples, respectively. Irrespective of the observed RAS, all patients responded well to DAA treatment, except for HCV1b-infected patients treated with Zepatier (33.3% failure rate (5/15)). Conclusion: While LiPA and FG-NGS showed overall good concordance, FG-NGS improved specificity for subtypes, recombinant and mixed infections. FG-NGS enabled the detection of RAS, but its predictive value for treatment outcome in DAA-naïve patients remains uncertain. With additional refinements, FG-NGS may be the way forward for HCV genotyping.publishersversionpublishe

Attribution of Plastic Sources Using Bayesian Inference: Application to River-Sourced Floating Plastic in the South Atlantic Ocean

Most marine plastic pollution originates on land. However, once plastic is at sea, it is difficult to determine its origin. Here we present a Bayesian inference framework to compute the probability that a piece of plastic found at sea came from a particular source. This framework combines information about plastic emitted by rivers with a Lagrangian simulation, and yields maps indicating the probability that a particle sampled somewhere in the ocean originates from a particular river source. We showcase the framework for floating river-sourced plastic released into the South Atlantic Ocean. We computed the probability as a function of the particle age at three locations, showing how probabilities vary according to the location and age. We computed the source probability of beached particles, showing that plastic found at a given latitude is most likely to come from the closest river source. This framework lays the basis for source attribution of marine plastic

Attribution of Plastic Sources Using Bayesian Inference: Application to River-Sourced Floating Plastic in the South Atlantic Ocean

Most marine plastic pollution originates on land. However, once plastic is at sea, it is difficult to determine its origin. Here we present a Bayesian inference framework to compute the probability that a piece of plastic found at sea came from a particular source. This framework combines information about plastic emitted by rivers with a Lagrangian simulation, and yields maps indicating the probability that a particle sampled somewhere in the ocean originates from a particular river source. We showcase the framework for floating river-sourced plastic released into the South Atlantic Ocean. We computed the probability as a function of the particle age at three locations, showing how probabilities vary according to the location and age. We computed the source probability of beached particles, showing that plastic found at a given latitude is most likely to come from the closest river source. This framework lays the basis for source attribution of marine plastic

Phylogenetic analysis of hepatitis C virus infections in a large Belgian cohort using next-generation sequencing of full-length genomes

Abstract: The hepatitis C virus (HCV) epidemic in Western countries is primarily perpetuated by the sub-populations of men who have sex with men (MSM) and people who inject drugs (PWID). Understanding the dynamics of transmission in these communities is crucial for removing the remaining hurdles towards HCV elimination. We sequenced 269 annotated HCV plasma samples using probe enrichment and next-generation sequencing, obtaining 224 open reading frames of HCV (OR497849-OR498072). Maximum likelihood phylogenies were generated on the four most prevalent subtypes in this study (HCV1a, 1b, 3a, 4d) with a subsequent transmission cluster analysis. The highest rate of clustering was observed for HCV4d samples (13/17 (76.47%)). The second highest rate of clustering was observed in HCV1a samples (42/78 (53.85%)) with significant association with HIV-positive MSM. HCV1b and HCV3a had very low rates of clustering (2/83 (2.41%) and (0/29)). The spread of the prevalent subtype HCV1b appears to have been largely curtailed, and we demonstrate the onwards transmission of HCV1a and HCV4d in the HIV-positive MSM population across municipal borders. More systematic data collection and sequencing is needed to allow a better understanding of the HCV transmission among the community of PWID and overcome the remaining barriers for HCV elimination in Belgium

Intestinal epithelial MyD88 is a sensor switching host metabolism towards obesity according to nutritional status

Obesity is associated with a cluster of metabolic disorders, low-grade inflammation and altered gut microbiota. Whether host metabolism is controlled by intestinal innate immune system and the gut microbiota is unknown. Here we report that inducible intestinal epithelial cell-specific deletion of MyD88 partially protects against diet-induced obesity, diabetes and inflammation. This is associated with increased energy expenditure, an improved glucose homeostasis, reduced hepatic steatosis, fat mass and inflammation. Protection is transferred following gut microbiota transplantation to germ-free recipients. We also demonstrate that intestinal epithelial MyD88 deletion increases anti-inflammatory endocannabinoids, restores antimicrobial peptides production and increases intestinal regulatory T cells during diet-induced obesity. Targeting MyD88 after the onset of obesity reduces fat mass and inflammation. Our work thus identifies intestinal epithelial MyD88 as a sensor changing host metabolism according to the nutritional status and we show that targeting intestinal epithelial MyD88 constitutes a putative therapeutic target for obesity and related disorders