Next-Generation Sequencing Center for GHOSTing Hepatitis C Virus: Transforming Community Based Molecular Surveillance and Outbreak Investigation

丙型肝炎病毒重影的下一代测序中心：改变基于社区的分子监测和疫情调查

• 批准号: 10241239
• 负责人: TODD M ALLEN
• 金额: $ 63.27万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10241239
• 关键词: Acute; Affect; American; Americas; Appalachian Region; Bioinformatics; Caring; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chronic; Collection; Communities; County; DNA Sequencing Facility; Data; Data Analyses; Data Storage and Retrieval; Deposition; Development; Diagnostic; Disease Outbreaks; Drug Prescriptions; Drug usage; Epidemic; Equipment; Event; Funding; General Hospitals; Generations; Goals; Grant; HIV; HIV Infections; Hepatitis; Hepatitis B Virus; Hepatitis C; Hepatitis C virus; Human Resources; Incidence; Indiana; Individual; Informatics; Infrastructure; Injecting drug user; Institutes; International; Intervention; Investigation; Laboratories; Link; Linux; Maintenance; Massachusetts; Molecular; National Institute of Allergy and Infectious Disease; Nature; Overdose; Participant; Pharmaceutical Preparations; Pharmacotherapy; Phylogenetic Analysis; Play; Procedures; Process; Program Research Project Grants; Quality Control; RNA amplification; Reporting; Research Personnel; Risk Factors; Role; Rural Community; SIV; Sampling; Serum; Shipping; Ships; Social Network; Specimen; Syphilis Serodiagnosis; System; Technology; Time; Training; United States; United States National Institutes of Health; United States Public Health Service; Validation; Variant; Viral; Viral hepatitis; Work; acute infection; analytical tool; base; clinical research site; community based participatory research; comorbidity; cost effective; design; experience; illicit opioid; improved; injection drug use; instrument; next generation sequencing; novel; opioid epidemic; opioid overdose; opioid use; pathogen; pathogenic virus; prescription opioid; prevent; public health intervention; response; rural area; transforming virus; transmission process; virology

PROJECT SUMMARY: The United States is in the midst of an enormous opioid epidemic. In 2015, more than 52,000 American's died due to a drug overdose, over 60% of which were associated with prescription or illicit opioid use. Given that injection drug use remains the major risk factor for HCV transmission, concomitantly the US has observed a striking >150% increase in the incidence of HCV between 2010-2013, and a 364% increase in new HCV infections between 2006 and 2012 in four Appalachian states, most notably in rural areas. As such, there is urgent need to more strategically detect, prevent, treat and control HCV on a national level. This U24 application proposes to develop a centralized GHOST laboratory to generate high-quality, high- throughput HCV NGS data for the CDC's GHOST center and accompanying clinical research sites to aid in the identification of HCV transmission links among persons who inject drugs (PWID); manage the collection and storage of serum samples from HIV- and HCV-infected participants from the clinical research sites under RFA- DA-17-014; and ship specimens to the CDC for syphilis testing and phylogenetic mapping for HIV and HCV. This proposal builds on the investigators' strong track record in generating large-scale Sanger and next- generation sequencing (NGS) data for highly variable pathogens such as HCV and HIV, development and maintenance of robust SOPs for reducing contamination and sample mix-up in large-scale NGS projects, and the development of robust NGS analysis platforms to enable real-time curation and storage of NGS data, downstream variant calling, and phylogenetic analysis. Dr. Allen's laboratory at the Ragon Institute of MGH, MIT and Harvard has been sequencing the highly variable pathogens HIV, HCV and SIV over the last 15 years during which time he has developed a well-established physical laboratory to support all stages of the laboratory process. He has also served as the PI of several viral sequencing cores on NIH/NIAID U01, U19 and P01 project grants during this time, thus providing extensive experience related to the cost-effective generation, curation, analysis, and deposition of sequence data for viral pathogens.

项目概要： 美国正处于阿片类药物的大规模流行之中。 2015年，超过52,000名美国人死亡 由于药物过量，其中超过 60% 与处方或非法使用阿片类药物有关。鉴于 注射吸毒仍然是丙型肝炎病毒传播的主要危险因素，同时美国也观察到 2010 年至 2013 年间，HCV 发病率显着增加 150% 以上，新发 HCV 增加 364% 2006 年至 2012 年间，阿巴拉契亚山脉的四个州都出现了感染病例，尤其是在农村地区。因此，有 迫切需要在国家层面上更具战略性地检测、预防、治疗和控制丙肝病毒。 该 U24 申请建议开发一个集中式 GHOST 实验室，以生成高质量、高质量的 为 CDC GHOST 中心和附属临床研究中心提供 HCV NGS 数据吞吐量，以帮助 查明注射吸毒者（PWID）之间的丙型肝炎病毒传播联系；管理集合并 RFA 下储存来自临床研究中心的 HIV 和 HCV 感染参与者的血清样本 DA-17-014；并将样本运送到 CDC 进行梅毒检测以及 HIV 和 HCV 的系统发育图谱。 该提案建立在研究人员在产生大规模桑格和下一步方面的良好记录之上。 HCV 和 HIV 等高度变异病原体的世代测序 (NGS) 数据、发育和 维护稳健的 SOP，以减少大规模 NGS 项目中的污染和样品混合，以及 开发强大的 NGS 分析平台，以实现 NGS 数据的实时管理和存储， 下游变异调用和系统发育分析。 艾伦博士位于麻省总医院、麻省理工学院和哈佛大学拉贡研究所的实验室一直在对高度变异的基因进行测序 在过去 15 年里，他对 HIV、HCV 和 SIV 病原体进行了深入研究，在此期间，他建立了一套行之有效的方法 物理实验室支持实验室过程的所有阶段。他还担任过多个病毒项目的 PI 在此期间，NIH/NIAID U01、U19 和 P01 项目资助的测序核心，从而提供了广泛的 与具有成本效益的病毒序列数据生成、管理、分析和存储相关的经验 病原体。