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HiDRA-seq: High-Throughput SARS-CoV-2 Detection by RNA Barcoding and Amplicon Sequencing

View ORCID ProfileEmilio Yángüez, Griffin White, Susanne Kreutzer, View ORCID ProfileLennart Opitz, View ORCID ProfileLucy Poveda, Timothy Sykes, Maria Domenica Moccia, View ORCID ProfileCatharine Aquino, View ORCID ProfileRalph Schlapbach
doi: https://doi.org/10.1101/2020.06.02.130484
Emilio Yángüez
1Functional Genomics Center Zurich (ETH/University of Zurich), Zurich, Switzerland
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  • For correspondence: emilio.yanguez@fgcz.ethz.ch
Griffin White
1Functional Genomics Center Zurich (ETH/University of Zurich), Zurich, Switzerland
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Susanne Kreutzer
1Functional Genomics Center Zurich (ETH/University of Zurich), Zurich, Switzerland
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Lennart Opitz
1Functional Genomics Center Zurich (ETH/University of Zurich), Zurich, Switzerland
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Lucy Poveda
1Functional Genomics Center Zurich (ETH/University of Zurich), Zurich, Switzerland
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Timothy Sykes
1Functional Genomics Center Zurich (ETH/University of Zurich), Zurich, Switzerland
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Maria Domenica Moccia
1Functional Genomics Center Zurich (ETH/University of Zurich), Zurich, Switzerland
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Catharine Aquino
1Functional Genomics Center Zurich (ETH/University of Zurich), Zurich, Switzerland
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Ralph Schlapbach
1Functional Genomics Center Zurich (ETH/University of Zurich), Zurich, Switzerland
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  • ORCID record for Ralph Schlapbach
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Abstract

The recent outbreak of a new coronavirus that causes a Severe Acute Respiratory Syndrome in humans (SARS-CoV-2) has developed into a global pandemic with over 6 million reported cases and more than 375,000 deaths worldwide. Many countries have faced a shortage of diagnostic kits as well as a lack of infrastructure to perform necessary testing. Due to these limiting factors, only patients showing symptoms indicating infection were subjected to testing, whilst asymptomatic individuals, who are widely believed to be responsible for the fast dispersion of the virus, were largely omitted from the testing regimes. The inability to implement high throughput diagnostic and contact tracing strategies has forced many countries to institute lockdowns with severe economic and social consequences. The World Health Organization (WHO) has encouraged affected countries to increase testing capabilities to identify new cases, allow for a well-controlled lifting of lockdown measures, and prepare for future outbreaks. Here, we propose HiDRA-seq, a rapidly implementable, high throughput, and scalable solution that uses NGS lab infrastructure and reagents for population-scale SARS-CoV-2 testing. This method is based on the use of indexed oligo-dT primers to generate barcoded cDNA from a large number of patient samples. From this, highly multiplexed NGS libraries are prepared targeting SARS-CoV-2 specific regions and sequenced. The low amount of sequencing data required for diagnosis allows the combination of thousands of samples in a sequencing run, while reducing the cost to approximately 2 CHF/EUR/USD per RNA sample. Here, we describe in detail the first version of the protocol, which can be further improved in the future to increase its sensitivity and to identify other respiratory viruses or analyze individual genetic features associated with disease progression.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 02, 2020.
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HiDRA-seq: High-Throughput SARS-CoV-2 Detection by RNA Barcoding and Amplicon Sequencing
Emilio Yángüez, Griffin White, Susanne Kreutzer, Lennart Opitz, Lucy Poveda, Timothy Sykes, Maria Domenica Moccia, Catharine Aquino, Ralph Schlapbach
bioRxiv 2020.06.02.130484; doi: https://doi.org/10.1101/2020.06.02.130484
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HiDRA-seq: High-Throughput SARS-CoV-2 Detection by RNA Barcoding and Amplicon Sequencing
Emilio Yángüez, Griffin White, Susanne Kreutzer, Lennart Opitz, Lucy Poveda, Timothy Sykes, Maria Domenica Moccia, Catharine Aquino, Ralph Schlapbach
bioRxiv 2020.06.02.130484; doi: https://doi.org/10.1101/2020.06.02.130484

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