Expanding Swabseq sequencing technology to enable readiness for emerging pathogens

扩展 Swabseq 测序技术，为新出现的病原体做好准备

• 批准号: 10719421
• 负责人: Valerie A Arboleda
• 金额: $ 57.35万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-11 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10719421
• 关键词: 2019-nCoV; Algorithmic Analysis; Area; Bar Codes; Biological Assay; CLIA certified; COVID-19; COVID-19 detection; COVID-19 pandemic; COVID-19 screening; COVID-19 testing; Calibration; Cessation of life; Clustered Regularly Interspaced Short Palindromic Repeats; Coccidioidomycosis; Collection; Communicable Diseases; Contact Tracing; Containment; Coupled; DNA; DNA sequencing; Detection; Diagnosis; Disease; Disease Outbreaks; Excision; Failure; Genomics; Goals; Health; Health Policy; Hospitalization; Hour; Human; Human poliovirus; Individual; Infection; International; Investments; Label; Laboratories; Light; Link; Masks; Mass Screening; Measures; Methodology; Methods; Molecular; Molecular Biology; Monkeypox; Nested PCR; Nucleic Acids; Patients; Persons; Poliomyelitis; Population; Probability; Process; Protocols documentation; Public Health; Quarantine; RNA; Rapid screening; Reaction; Readiness; Reagent; Research; Reverse Transcriptase Polymerase Chain Reaction; Reverse Transcription; Running; Sampling; Series; Specimen; Swab; Symptoms; Technology; Test Result; Testing; Time; Travel; Tube; Vaccination; Variant; Viral; Virus; Vision; Work; clinical development; clinical diagnostics; combinatorial; commensal bacteria; cost; current pandemic; desert fever; design; detection limit; detection method; emerging pathogen; flexibility; future pandemic; high throughput screening; improved; indexing; innovation; next generation; next generation sequencing; novel; pandemic disease; pandemic response; pathogen; pathogenic bacteria; pathogenic fungus; pathogenic virus; research clinical testing; saliva sample; scale up; surveillance network; technology development; transcriptome sequencing; transmission process; variant detection; viral detection

This application aims to develop improved methods for detecting novel pathogens that can be deployed on a large scale and are flexible to multiple pathogens. The method uses the power of next generation sequencing technology to analyse hundreds of thousands of samples simultaneously. In contrast to standard clinical testing, where one person's sample is tested in a single tube, mass testing labels each person's sample with a unique piece of DNA that acts as a molecular barcode, then pools multiple samples together so that they can be jointly tested. DNA sequencing is then used to detect those samples with virus in the pool of hundreds of thousands of individuals, and assign the virus to the samples it came from on the basis of the molecular barcodes. A bench top sequencer can process tens of thousands a day. A larger machine generates enough sequence to run up to hundreds of thousands of tests in one day. Our aim is to make it possible for a moderately well-equipped molecular biology laboratory to be able to process tens of thousands of samples without much investment. We have successfully deployed SwabSeq testing at the high-complexity, CLIA-certified, UCLA SwabSeq COVID19 Testing laboratory. Our work has demonstrated the utility for high-throughput asymptomatic testing and with additional improvements can increase testing capacity by orders of magnitude, making it possible to deploy testing on a population scale. Our sequencing-based approach can be extended to also detect viral variants at the same time and to other viral pathogens. Mass testing will f nd asymptomatic carriers and thus inform public health policies so that containment of infection will be effective.

这项应用旨在开发改进的方法来检测新的病原体，这些方法可以大规模部署，并对多种病原体灵活。该方法利用下一代测序技术的力量，同时分析数十万个样本。与标准临床测试不同的是，一个人的样本在一个试管中进行测试，批量测试将每个人的样本标记上一段独特的DNA，充当分子条形码，然后将多个样本放在一起，以便可以联合测试。然后，DNA测序被用来检测那些在数十万人的池中带有病毒的样本，并根据分子条形码将病毒分配给它来自的样本。一台台式测序仪每天可以处理数万台测序仪。一台较大的机器生成的序列足以在一天内运行多达数十万个测试。我们的目标是使一个设备适度、设备精良的分子生物学实验室能够在不需要太多投资的情况下处理数万个样本。我们已在加州大学洛杉矶分校通过CLIA认证的高复杂性SwabSeq COVID19测试实验室成功部署了SwabSeq测试。我们的工作已经证明了高通量无症状测试的实用性，通过额外的改进可以将测试容量增加数量级，使在人口规模上部署测试成为可能。我们基于测序的方法可以扩展到同时检测病毒变异和其他病毒病原体。大规模检测将发现无症状携带者，从而为公共卫生政策提供信息，从而遏制感染 要有效率。