Bioinformatics Framework for Wastewater-based Surveillance of Infectious Diseases

摘要 使人们能够获得全面的生物医学信息是美国国家图书馆使命的核心 医学是疾病预防的关键，有助于改善国家和全球的健康状况。在……方面 传染病预防、实时和无偏见的序列数据对于早期发现 减少暴发、流行病和流行病的威胁。这项拟议的研究项目旨在创新 创建和获取与传染病病原体有关的元基因组序列数据 废水流行病学(WBE)的潜在变革性工具。WBE方法使用分析 对大量人口的社区废水进行非侵入性、接近实时的监控 有症状和无症状的个体。当与高通量元基因组测序结合时 (HTS)，由此产生的WBE-HTS方法有望用于检测广泛的感染性病原体 同时，没有任何关于病毒身份或存在的先验假设。该项目将测试 假设对在美国可检测到的病毒的聚合元基因组序列数据的处理。 废水可用于及早识别脆弱性、疫情和流行病，从而创造一种新的和 可能挽救生命的诊断方法，以保护公众健康。 为了进行假设检验，该团队将利用亚利桑那州立大学的人类健康天文台(HHO)， 世界上最大的污水监测网络和最大的污水和污泥样本档案， 代表美国200多个城市和全球300多个城市。 这项工作的总体目标是开发一个广泛适用的在线生物信息学框架，并 在使用WBE和HTS的案例研究中展示其有效性。 这三个具体目标是：(1)在一个全面的数据库中盘点美国现存的病毒，使用 现有数据库资源和WBE；(Ii)创建元基因组学知识库和在线门户网站 数据，以支持对人类相关病毒的近乎实时的监测，以及(3)评估 WBE生物信息学框架，用于跟踪病毒爆发和流行。 该项目的顺利完成将为美国提供病原体预警系统 可用于预防流行病的检测和疫情跟踪，从而降低发病率和死亡率 在美国，首先是病毒，未来可能是致病菌和 其他生物危害。

Abstract Enabling access to comprehensive biomedical information is central to the mission of the National Library of Medicine and key to disease prevention for better health outcomes nationally and globally. In the area of infectious disease prevention, real time and non-biased sequence data are essential for early detection of threats to mitigate outbreaks, epidemics and pandemics. This proposed research project aims to innovate in the creation and accessibility of metagenomic sequence data relating to infectious agents by leveraging the potentially transformative tool of wastewater-based epidemiology (WBE). The WBE approach employs analysis of community wastewater from large populations to enable non-invasive, near real-time monitoring of both symptomatic and asymptomatic individuals. When combined with high-throughput metagenomic sequencing (HTS), the resulting WBE-HTS approach is promising for detecting a broad spectrum of infectious agents simultaneously without any a priori assumptions about virus identity or presence. This project will test the hypothesis that the processing of aggregated metagenomic sequence data on viruses detectable in U.S. wastewater can serve to identify vulnerabilities, outbreaks and epidemics early, thereby creating a novel and potentially life-saving diagnostic approach for protecting public health. For hypothesis testing, the team will leverage Arizona State University's Human Health Observatory (HHO), the largest sewage monitoring network and largest archive of sewage and sludge samples worldwide, representing more than 200 U.S. cities and over 300 cities globally. The overall goal of this work is to develop a broadly applicable online bioinformatics framework and to demonstrate its utility in a case study employing WBE and HTS. The three specific aims are to: (i) inventory viruses extant in the U.S. in a comprehensive database, using existing database sources and WBE; (ii) generate a knowledge repository and online portal of metagenomic data to support near real-time surveillance of the human–associated virome, and (iii) evaluate the utility of the WBE bioinformatics framework for tracking viral outbreaks and epidemics. Successful completion of this project will provide the U.S. with an early warning system for pathogen detection and outbreak tracking that can serve to prevent epidemics, thereby reducing morbidity and mortality in the U.S. from contagious pathogens, first for viruses and potentially in the future for pathogenic bacteria and other biohazards.