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国家图书馆使命的核心。 医学和疾病预防的关键，以改善国家和全球的健康结果。领域的 传染病预防、真实的时间和无偏差的序列数据对于早期检测 减轻疾病爆发、流行病和大流行病的威胁。该研究项目旨在创新 创建和访问与感染因子相关的宏基因组序列数据， 基于废水的流行病学（WBE）的潜在变革工具。WBE方法采用分析 从大量人口的社区废水，使非侵入性，近实时监测两者 有症状和无症状的个体。当与高通量宏基因组测序相结合时， (HTS)，由此产生的WBE-HTS方法有希望用于检测广谱的感染因子 同时没有关于病毒身份或存在的任何先验假设。该项目将测试 假设对在美国可检测的病毒的聚集宏基因组序列数据的处理 废水可有助于及早发现脆弱性、疾病爆发和流行病，从而创造一种新的 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观察站（HHO）， 全球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， 证明其效用的案例研究采用WBE和HTS。 三个具体目标是：（i）在一个综合数据库中清点美国现存的病毒，使用 现有的数据库资源和WBE;（ii）生成宏基因组的知识库和在线门户网站 数据，以支持人类相关病毒组的近实时监测，以及（iii）评估 用于追踪病毒爆发和流行的WBE生物信息学框架。 该项目的成功完成将为美国提供病原体预警系统 检测和疫情跟踪，可用于预防流行病，从而降低发病率和死亡率 在美国，传染性病原体，首先是病毒，未来可能是致病细菌， 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.