On-site, high-fidelity target sequencing and absolute quantitation for HIV-1 surveillance

用于 HIV-1 监测的现场高保真目标测序和绝对定量

• 批准号: 9625001
• 负责人: Sanggu Kim
• 金额: $ 83.3万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9625001
• 关键词: AIDS/HIV problem; Area; Biological; Biological Assay; Biological Sciences; Biotechnology; Care Technology Points; Clinic; Clinical; Communicable Diseases; Complex; DNA; Data; Data Analyses; Devices; Diagnosis; Diagnostic; Drug resistance; Educational Background; Engineering; Ensure; Environment; Epidemic; Generations; Genetic Population Study; Genetic Variation; Genome; Genotype; Goals; HIV; HIV-1; HIV-1 drug resistance; Laboratories; Length; Libraries; Mediating; Medicine; Methods; Molecular; Ohio; Output; Pathogen detection; Patient Care; Patients; Population; Population Dynamics; Positioning Attribute; Preventive Intervention; Price; Procedures; Reading; Research; Resources; Science; Sequence Analysis; Site; Standardization; Technology; Testing; Third Generation Sequencing; Time; Twin Multiple Birth; Universities; Variant; Viral; Virus; antimicrobial drug; antiretroviral therapy; cancer cell; chemical synthesis; cost; genetic variant; genome sequencing; genome-wide; high throughput technology; improved; innovation; instrument; microbial; multidisciplinary; nanopore; next generation sequencing; novel; pathogen; point of care; portability; sequencing platform; single molecule; success; whole genome

PROJECT SUMMARY / ABSTRACT UNAIDS has set ambitious 90/90/90 targets toward ending the HIV/AIDS epidemic: that by 2020, 90% of people living with HIV will know their HIV status; 90% of those diagnosed will be on sustained antiretroviral treatment; and 90% of those on treatment will have achieved viral suppression. Reaching these goals will require precise and efficient testing, patient care, and prevention interventions for key populations, particularly in resource-limited settings. The genetic diversity of microbial pathogens – not just HIV-1 but any number of pathogens for which antimicrobial drugs are being developed/employed – remains a major challenge for those endeavoring to control them. Drug-resistance surveillance and the genotyping of microbial pathogens have long been plagued by limited read lengths and erroneous sequencing. The proposed project will develop an innovative sequencing and quantitation platform technology that can sensitively detect and accurately delineate HIV-1 variants in patients through barcode-mediated, whole-genome sequencing using the so-called “third-generation” Nanopore sequencing technology (Aims 1 and 2). Taking advantage of the pocket-size mobility of the MinION Nanopore sequencer and other portable biotechnology devices that have recently became available, we will further develop this technology for on-site and real-time surveillance and drug- resistance diagnosis of emerging viruses even in resource-limited settings (Aim 3). Successful completion of this study will produce a low-cost, ultra-high-accuracy sequencing and quantitation technology with broad applicability to problems in diverse areas of science and medicine, from de novo genome assembly to point-of- care drug-resistance genotyping. HIV-1 offers an excellent testbed for this technology due to the high degree intra-patient genetic diversity and the need for on-site and genome-wide genotyping.

项目摘要 /摘要 UNAIDS已将雄心勃勃的90/90/90目标设定为艾滋病毒/艾滋病流行：到2020年，90％ 患有艾滋病毒的人会知道自己的艾滋病毒状况。 90％的被诊断患者将用于持续的抗逆转录病毒 治疗; 90％的治疗方法将实现病毒抑制。实现这些目标将 需要精确有效的测试，患者护理和预防干预措施，特别是 在资源有限的设置中。微生物病原体的遗传多样性 - 不仅是HIV-1，而且有任何数量 开发/使用抗菌药物的病原体 - 对于那些人来说仍然是一个主要挑战 努力控制它们。耐药性监测和微生物病原体的基因分型具有 长期以来，读取长度和错误的测序困扰着。拟议的项目将开发 创新的测序和定量平台技术，可以灵敏，准确地检测 通过条形码介导的全基因组测序，使用所谓 “第三代”纳米孔测序技术（目标1和2）。利用袖珍尺寸 Minion Nanobore测序仪和其他便携式生物技术设备的移动性 成为可用 即使在资源有限的设置中，新兴病毒的阻力诊断（AIM 3）。成功完成 这项研究将产生低成本，超高准确的测序和量化技术 从从头基因组组装到科学和医学潜水区的问题，适用于 - 护理药物抗药性基因分型。 HIV-1由于高度而为该技术提供了出色的测试床 门内遗传多样性以及对全基因组和基因组基因分型的需求。