Nanopore target sequencing for accurate and comprehensive detection of SARS-CoV-2 and other respiratory viruses

Wang, Ming; Fu, Aisi; Hu, Ben; Tong, Yongqing; Liu, Ran; Gu, Jiashuang; Liu, Jianghao; Jiang, Wen; Shen, Gaigai; Zhao, Wenhui; Men, Dong; Deng, Zixin; Yu, Lilei; Liu, Tiangang

doi:10.1101/2020.03.04.20029538

Cited by 32 publications

(42 citation statements)

References 35 publications

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“…Based on median and mean estimates, we have on average a mutation accumulation rate of half a dozen per patient. Although there have been data reported from single-molecule sequencing platform but they are low in coverage [39].…”

Section: Resultsmentioning

confidence: 99%

Compositional Variability and Mutation Spectra of Monophyletic SARS-CoV-2 Clades

Teng

Zhao

et al. 2020

Preprint

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COVID-19 and its causative pathogen SARS-CoV-2 have rushed the world into a staggering pandemic in a few months and a global fight against both is still going on. Here, we describe an analysis procedure where genome composition and its variables are related, through the genetic code, to molecular mechanisms based on understanding of RNA replication and its feedback loop from mutation to viral proteome sequence fraternity including effective sites on replicase-transcriptase complex. Our analysis starts with primary sequence information and identity-based phylogeny based on 22,051 SARS-CoV-2 genome sequences and evaluation of sequence variation patterns as mutation spectrum and its 12 permutations among organized clades tailored to two key mechanisms: strand-biased and function-associated mutations. Our findings include: (1) The most dominant mutation is C-to-U permutation whose abundant second-codon-position counts alter amino acid composition toward higher molecular weight and lower hydrophobicity albeit assumed most slightly deleterious. (2) The second abundance group includes: three negative-strand mutations U-to-C, A-to-G, G-to-A and a positive-strand mutation G-to-U generated through an identical mechanism as C-to-U. (3) A clade-associated and biased mutation trend is found attributable to elevated level of the negative-sense strand synthesis. (4) Within-clade permutation variation is very informative for associating non-synonymous mutations and viral proteome changes. These findings demand a bioinformatics platform where emerging mutations are mapped on to mostly subtle but fast-adjusting viral proteomes and transcriptomes to provide biological and clinical information after logical convergence for effective pharmaceutical and diagnostic applications. Such thoughts and actions are in desperate need, especially in the middle of the War against COVID-19.

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Section: Resultsmentioning

confidence: 99%

Compositional Variability and Mutation Spectra of Monophyletic SARS-CoV-2 Clades

Teng

Zhao

et al. 2020

Preprint

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“…NTS identified positive to 22 of 61 suspected COVID-19 specimens that were either negative or inconclusive by RT-PCR. Screening mutations showed that 4 of 19 throat swab samples from COVID-19 patients were found single-nucleotide mutations at seven sites [97]. These findings suggested that NTS is suitable for the identification and mutation monitoring of SARS-CoV-2 from clinical samples.…”

Section: Genomic Sequencing In Sars-cov-2mentioning

confidence: 92%

“…As of March 2020, hundreds of SARS-CoV-2 genomes were released on public databases including Global initiative on sharing all influenza data (GISAID), NCBI GenBank and China National GeneBank DataBase (CNGBdb). At present, sequencing methods of SARS-CoV-2 include metatranscriptomics sequencing [27], hybrid capture-based sequencing [96], amplicon sequencing [96], and nanopore targeted sequencing [97]. The advantages and disadvantages of SARS-CoV-2 genomic sequencing are shown in Table 1.…”

Section: Genomic Sequencing In Sars-cov-2mentioning

confidence: 99%

Laboratory diagnosis of coronavirus disease-2019 (COVID-19)

Zhao

Bao

et al. 2020

Clinica Chimica Acta

134

116

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The outbreak of Coronavirus Disease-2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has threatened health worldwide. As of the end of 2020, there were nearly 10 million confirmed cases and nearly 5 million deaths associated with COVID-19. Rapid and early laboratory diagnosis of COVID-19 is the main focus of treatment and control. Molecular tests are the basis for confirmation of COVID-19, but serological tests for SARS-CoV-2 are widely available and play an increasingly important role in understanding the epidemiology of the virus and in identifying populations at higher risk for infection. Pointof-care tests have the advantage of rapid, accurate, portable, low cost and non-specific device requirements, which provide great help for disease diagnosis and detection. This review will discuss the performance of different laboratory diagnostic tests and platforms, as well as suitable clinical samples for testing, and related biosafety protection. This review shall guide for the diagnosis of COVID-19 caused by SARS-CoV-2.

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“…Moreover, it could identify 40 other respiratory viruses and monitor changes in virulence and transmissibility caused by viral mutations. 109 Therapeutic agents All patients should be treated in isolation. 53 Based on previous studies, drugs may be developed to inhibit cell entry.…”

Section: Diagnosis and Therapy Diagnostic Methodsmentioning

confidence: 99%

Overview of lethal human coronaviruses

Chen

Tian

et al. 2020

Sig Transduct Target Ther

260

236

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Coronavirus infections of multiple origins have spread to date worldwide, causing severe respiratory diseases. Seven coronaviruses that infect humans have been identified: HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2. Among them, SARS-CoV and MERS-CoV caused outbreaks in 2002 and 2012, respectively. SARS-CoV-2 (COVID-19) is the most recently discovered. It has created a severe worldwide outbreak beginning in late 2019, leading to date to over 4 million cases globally. Viruses are genetically simple, yet highly diverse. However, the recent outbreaks of SARS-CoV and MERS-CoV, and the ongoing outbreak of SARS-CoV-2, indicate that there remains a long way to go to identify and develop specific therapeutic treatments. Only after gaining a better understanding of their pathogenic mechanisms can we minimize viral pandemics. This paper mainly focuses on SARS-CoV, MERS-CoV, and SARS-CoV-2. Here, recent studies are summarized and reviewed, with a focus on virus-host interactions, vaccine-based and drug-targeted therapies, and the development of new approaches for clinical diagnosis and treatment.

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Nanopore target sequencing for accurate and comprehensive detection of SARS-CoV-2 and other respiratory viruses

Cited by 32 publications

References 35 publications

Compositional Variability and Mutation Spectra of Monophyletic SARS-CoV-2 Clades

Compositional Variability and Mutation Spectra of Monophyletic SARS-CoV-2 Clades

Laboratory diagnosis of coronavirus disease-2019 (COVID-19)

Overview of lethal human coronaviruses

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