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arXiv 2005.07895q-bio.QM
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一种用于COVID-19检测的RT-PCR池测试压缩感知方法

A Compressed Sensing Approach to Pooled RT-PCR Testing for COVID-19 Detection

Sabyasachi Ghosh, Rishi Agarwal, Mohammad Ali Rehan, Shreya Pathak, Pratyush Agrawal, Yash Gupta, Sarthak Consul, Nimay Gupta, Ritika, Ritesh Goenka, Ajit Rajwa… 展开作者

Sabyasachi Ghosh, Rishi Agarwal, Mohammad Ali Rehan, Shreya Pathak, Pratyush Agrawal, Yash Gupta, Sarthak Consul, Nimay Gupta, Ritika, Ritesh Goenka, Ajit Rajwade, Manoj Gopalkrishnan

摘要:

我们提出了“Tapestry”,这是一种新的混合检测方法,可应用于COVID-19定量逆转录聚合酶链反应(RT-PCR)检测,从而缩短检测时间并节省试剂和检测试剂盒。Tapestry将压缩传感和组合组测试的思想与用于生成合成数据的RT-PCR的新噪声模型相结合。与布尔组检验算法不同,输入是来自每个测试的定量读数,输出是每个样本相对于具有最高病毒载量的池的病毒载量列表。虽然其他合并技术需要第二次确证性测定,但Tapestry在单轮测试中以临床上可接受的假阳性或假阴性率获得单个样品水平的结果。我们还提出了合并矩阵的设计,便于良好的预测感染的样本,同时保持实际可行的。当测试$k \ll n$被感染的$n$样本时,当使用随机二进制池化矩阵时,我们的方法仅需要$O(k \log n)$测试,具有高概率。然而,我们也使用基于Kirkman三重系统的组合设计思想的确定性二进制池化矩阵,以在良好的重构特性和矩阵稀疏性之间进行平衡,以便于池化。在实践中,我们已经观察到需要较少的测试与这些矩阵比随机池矩阵。这使得Tapestry能够在低流行率下节省大量资金,同时即使在高达9.5%的流行率下也保持可行性。根据经验,我们发现单轮Tapestry池比两轮Dorfman池在所需的测试数量上提高了近2倍。我们在模拟和湿实验室实验中验证Tapestry,并在定量RT-PCR分析中使用寡聚体。最后,我们描述部署的用例场景。

英文摘要:

We propose `Tapestry', a novel approach to pooled testing with application to COVID-19 testing with quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) that can result in shorter testing time and conservation of reagents and testing kits. Tapestry combines ideas from compressed sensing and combinatorial group testing with a novel noise model for RT-PCR used for generation of synthetic data. Unlike Boolean group testing algorithms, the input is a quantitative readout from each test and the output is a list of viral loads for each sample relative to the pool with the highest viral load. While other pooling techniques require a second confirmatory assay, Tapestry obtains individual sample-level results in a single round of testing, at clinically acceptable false positive or false negative rates. We also propose designs for pooling matrices that facilitate good prediction of the infected samples while remaining practically viable. When testing $n$ samples out of which $k \ll n$ are infected, our method needs only $O(k \log n)$ tests when using random binary pooling matrices, with high probability. However, we also use deterministic binary pooling matrices based on combinatorial design ideas of Kirkman Triple Systems to balance between good reconstruction properties and matrix sparsity for ease of pooling. In practice, we have observed the need for fewer tests with such matrices than with random pooling matrices. This makes Tapestry capable of very large savings at low prevalence rates, while simultaneously remaining viable even at prevalence rates as high as 9.5\%. Empirically we find that single-round Tapestry pooling improves over two-round Dorfman pooling by almost a factor of 2 in the number of tests required. We validate Tapestry in simulations and wet lab experiments with oligomers in quantitative RT-PCR assays. Lastly, we describe use-case scenarios for deployment.

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