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Application of Next-Generation Sequencing to Reveal How Evolutionary Dynamics of Viral Population Shape Dengue Epidemiology.

ABSTRACT: Dengue viral (DENV) infection results in a wide spectrum of clinical manifestations from asymptomatic, mild fever to severe hemorrhage diseases upon infection. Severe dengue is the leading cause of pediatric deaths and/or hospitalizations, which are a major public health burden in dengue-endemic or hyperendemic countries. Like other RNA viruses, DENV continues to evolve. Adaptive mutations are obscured by the major consensus sequence (so-called wild-type sequences) and can only be identified once they become the dominant viruses in the virus population, a process that can take months or years. Traditional surveillance systems still rely on Sanger consensus sequencing. However, with the recent advancement of high-throughput next-generation sequencing (NGS) technologies, the genome-wide investigation of virus population within-host and between-hosts becomes achievable. Thus, viral population sequencing by NGS can increase our understanding of the changing epidemiology and evolution of viral genomics at the molecular level. This review focuses on the studies within the recent decade utilizing NGS in different experimental and epidemiological settings to understand how the adaptive evolution of dengue variants shapes the dengue epidemic and disease severity through its transmission. We propose three types of studies that can be pursued in the future to enhance our surveillance for epidemic prediction and better medical management.

SUBMITTER: Ko H

PROVIDER: S-EPMC7318875 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Project description:BackgroundMetagenomic next-generation sequencing (mNGS) technology has been widely used to diagnose various infections. Based on the most common pathogen profiles, targeted mNGS (tNGS) using multiplex PCR has been developed to detect pathogens with predesigned primers in the panel, significantly improving sensitivity and reducing economic burden on patients. However, there are few studies on summarizing pathogen profiles of pulmonary infections in immunocompetent and immunocompromised patients in Jilin Province of China on large scale.MethodsFrom January 2021 to December 2023, bronchoalveolar lavage fluid (BALF) or sputum samples from 546 immunocompetent and immunocompromised patients with suspected community-acquired pneumonia were collected. Pathogen profiles in those patients on whom mNGS was performed were summarized. Additionally, we also evaluated the performance of tNGS in diagnosing pulmonary infections.ResultsCombined with results of mNGS and culture, we found that the most common bacterial pathogens were Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii in both immunocompromised and immunocompetent patients with high detection rates of Staphylococcus aureus and Enterococcus faecium, respectively. For fungal pathogens, Pneumocystis jirovecii was commonly detected in patients, while fungal infections in immunocompetent patients were mainly caused by Candida albicans. Most of viral infections in patients were caused by Human betaherpesvirus 5 and Human gammaherpesvirus 4. It is worth noting that, compared with immunocompetent patients (34.9%, 76/218), more mixed infections were found in immunocompromised patients (37.8%, 14/37). Additionally, taking final comprehensive clinical diagnoses as reference standard, total coincidence rate of BALF tNGS (81.4%, 48/59) was much higher than that of BALF mNGS (40.0%, 112/280).ConclusionsOur findings supplemented and classified the pathogen profiles of pulmonary infections in immunocompetent and immunocompromised patients in Jilin Province of China. Most importantly, our findings can accelerate the development and design of tNGS specifically used for regional pulmonary infections.

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Application of Next-Generation Sequencing to Reveal How Evolutionary Dynamics of Viral Population Shape Dengue Epidemiology.

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