Expanding Swabseq sequencing technology to enable readiness for emerging pathogens

该申请旨在开发用于检测新型病原体的改进方法，这些方法可以大规模部署，并且对多种病原体具有灵活性。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。与标准的临床测试不同，一个人的样本在一个试管中进行测试，大规模测试用一个独特的DNA片段标记每个人的样本，作为分子条形码，然后将多个样本汇集在一起，以便它们可以进行联合测试。然后，DNA测序用于在数十万个体的池中检测那些带有病毒的样本，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个。一台更大的机器生成足够的序列，可以在一天内运行多达数十万个测试。我们的目标是使一个装备精良的分子生物学实验室能够在没有太多投资的情况下处理数万个样品。我们已在高复杂性、CLIA认证的UCLA SwabSeq COVID 19检测实验室成功部署SwabSeq检测。我们的工作已经证明了高通量无症状测试的实用性，并通过额外的改进可以提高测试容量的数量级，使其有可能在人口规模上部署测试。我们基于测序的方法可以扩展到同时检测病毒变体和其他病毒病原体。大规模检测将发现无症状的携带者，从而为公共卫生政策提供信息， 要有效率。

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.