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Large-scale testing and tracking of SARS-CoV-2 infection and evolution by deep sequencing

English title Large-scale testing and tracking of SARS-CoV-2 infection and evolution by deep sequencing
Applicant Reddy Sai
Number 196348
Funding scheme Special Call on Coronaviruses
Research institution Departement für Biosysteme und Ingenieurwissenschaften ETH Zürich
Institution of higher education ETH Zurich - ETHZ
Main discipline Infectious Diseases
Start/End 01.07.2020 - 30.06.2022
Approved amount 184'872.00
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All Disciplines (2)

Discipline
Infectious Diseases
Molecular Biology

Keywords (3)

machine learning; high-throughput; deep sequencing

Lay Summary (German)

Lead
High-throughput testing for COVID-19
Lay summary

Um die COVID-19-Pandemie zu bekämpfen, setzen die Länder auf nicht-pharmazeutische Interventionen (NPI), die sich sozial und wirtschaftlich dramatisch auswirken. Ein zentrales Problem ist der Mangel an Diagnose- und Überwachungskapazitäten, um die Übertragung und Infektion von COVID-19 auf Bevölkerungsebene besser zu verstehen. In diesem Projekt entwickeln wir ein umfangreiches Testprotokoll für COVID-19-Infektionen durch Tiefensequenzierung. Es basiert auf einer molekularen Barcode-Technologie zum Nachweis einer SARS-CoV-2-Infektion, mit der wir bis zu 5.000 Patientenproben in einem einzigen Tiefensequenzierungsexperiment angemessen testen können. Unser Ansatz würde ein schnelles Diagnoserahmenwerk mit hohem Durchsatz bieten. Darüber hinaus können wir die molekularen Sequenzinformationen zur Verfolgung der Ausbreitung und Entwicklung des Virus in der ganzen Schweiz verwenden. Diese Sequenzierungsdaten können dann verwendet werden, um Übertragungsketten zu rekonstruieren und weitere Maßnahmen im Bereich der öffentlichen Gesundheit wie die Quarantäne zu informieren.

Direct link to Lay Summary Last update: 04.08.2020

Responsible applicant and co-applicants

Abstract

The global pandemic of Coronavirus infectious disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented an acute and global health challenge of a magnitude not experienced in over a century. To combat the COVID-19 pandemic, countries are relying on non-pharmaceutical interventions (quarantines, social distancing, shutdown of non-essential businesses), which are having a dramatic social and economic impact. A central problem is the lack of diagnostics and surveillance capacities, which are essential for detecting SARS-CoV-2 infections and subsequently reducing transmission chains through effective NPI. Current molecular diagnostics (qRT-PCR assays) are limited in throughput (e.g., 7’000 total per day in Switzerland) and do not provide viral molecular sequence information for epidemiology.To overcome the limitations in current COVID-19 testing, we will develop a molecular barcoding method to tag individual patient RNA samples, which will then be highly multiplexed and tested for detection of virus by deep sequencing and bioinformatics. The importance of molecular barcodes is that they will be connected to a patient identification sample, meaning that on a single deep sequencing run (e.g., Illumina MiSeq) we will be able to multiplex and test up to 4,800 patient samples (Aim 1). Furthermore, our deep sequencing-based testing assay will also allow us to perform evolutionary analysis; by selectively sequencing regions of viral diversity, we will obtain molecular sequence information tracking the spread and evolution of the virus throughout Switzerland (Aim 2). This sequencing data will then be used to recreate transmission chains and inform further quarantine and social distancing measures. Our preliminary estimates suggest that we can sequence 4,800 samples (50 distinct 96-well plates) within a single MiSeq run in less than 24 hours. This can easily be scaled up based on the number of available patient samples by either increasing the number of sequencing runs in parallel (across multiple machines) or by using a higher throughput sequencing machine. This simple molecular biology assay can also be transferred to almost any diagnostics lab in the world, within Switzerland there are at least 30 sites where testing centers could be established and the sequencing infrastructure is available to likely achieve 2,000,0000 samples per week. With this capacity, it would only take 4 weeks for all of Switzerland to be tested for SARS-CoV-2 infection.
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