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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Exposing malaria in-host diversity and estimating population diversity by capture-recapture using massively parallel pyrosequencing
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Exposing malaria in-host diversity and estimating population diversity by capture-recapture using massively parallel pyrosequencing

机译：使用大规模并行焦磷酸测序揭示宿主内的疟疾多样性并通过捕获-再捕获估算种群多样性

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摘要

Malaria infections commonly contain multiple genetically distinct variants. Mathematical and animal models suggest that interactions among these variants have a profound impact on the emergence of drug resistance. However, methods currently used for quantifying parasite diversity in individual infections are insensitive to low-abundance variants and are not quantitative for variant population sizes-. To more completely describe the in-host complexity and ecology of malaria infections, we used massively parallel pyrosequencing to characterize malaria parasite diversity in the infections of a group of patients. By individually sequencing single strands of DNA in a complex mixture, this technique can quantify uncommon variants in mixed infections. The in-host diversity revealed by this method far exceeded that described by currently recommended genotyping methods, with as many as sixfold more variants per infection. In addition, in paired pre- and posttreatment samples, we show a complex milieu of parasites, including variants likely up-selected and down-selected by drug therapy. As with all surveys of diversity, sampling limitations prevent full discovery and differences in sampling effort can confound comparisons among samples, hosts, and populations. Here, we used ecological approaches of species accumulation curves and capture-recapture to estimate the number of variants we failed to detect in the population, and show that these methods enable comparisons of diversity before and after treatment, as well as between malaria populations. The combination of ecological statistics and massively parallel pyrosequencing provides a powerful tool for studying the evolution of drug resistance and the in-host ecology of malaria infections.
机译：疟疾感染通常包含多种遗传上不同的变异。数学和动物模型表明，这些变体之间的相互作用对耐药性的产生具有深远的影响。但是，当前用于量化个体感染中寄生虫多样性的方法对低丰度变体不敏感，并且对于变体种群大小不定量。为了更完整地描述宿主内部的疟疾感染的复杂性和生态学，我们使用了大规模平行焦磷酸测序来表征一组患者感染中的疟原虫多样性。通过对复杂混合物中的DNA单链进行单独测序，该技术可以量化混合感染中不常见的变体。通过这种方法揭示的宿主内部多样性远远超过了目前推荐的基因分型方法所描述的多样性，每个感染的变体多达六倍。此外，在成对的治疗前和治疗后样本中，我们显示了复杂的寄生虫环境，包括可能通过药物疗法上调和下调的变体。与所有多样性调查一样，抽样限制会阻止全面发现，抽样工作的差异会混淆样本，宿主和人群之间的比较。在这里，我们使用了物种积累曲线和捕获-捕获的生态方法来估计我们未能在种群中发现的变体数量，并表明这些方法能够比较治疗前后以及疟疾种群之间的多样性。生态统计学和大规模并行焦磷酸测序的结合为研究耐药性的演变和疟疾感染的宿主生态学提供了强大的工具。

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    Jonathan J. Juliano; Kimberly Porter; Victor Mwapasa; Rithy Sem; William O. Rogers; Frederic Ariey; Chansuda Wongsrichanalai; Andrew Read; Steven R. Meshnick;

  • 作者单位

    Division of Infectious Diseases, School of Medicine, University of North Carolina, Chapel Hill, NC 27514;

    Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27514;

    Department of Community Health, University of Malawi College of Medicine, Blantyre 3, Malawi;

    The National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia;

    Naval Medical Research Unit No. 2, Pearl Harbor, HI 96860;

    Institut Pasteur du Cambodge, Phnom Penh, Cambodia;

    Naval Medical Research Unit No. 2, Pearl Harbor, HI 96860;

    Centre for Infectious Disease Dynamics, Departments of Biology and Entomology, Penn State University, University Park, PA 16802,Fogarty International Center, National Institutes of Health, Bethesda, MD 20892;

    Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27514;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    plasmodium falciparum; next generation sequencing;

    机译：恶性疟原虫下一代测序;

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