Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Systematic surveillance of SARS-CoV-2 reveals dynamics of variant mutagenesis and transmission in a large urban population II

ABSTRACT: Highly mutable pathogens generate viral diversity that impacts virulence, transmissibility, treatment, and thwarts acquired immunity. We previously described C19-SPAR-Seq, a high-throughput, next-generation sequencing platform to detect SARS-CoV-2 that we deployed to systematically profile variant dynamics of SARS-CoV-2 for over 3 years in a large, North American urban environment (Toronto, Canada). Sequencing of the ACE2 receptor binding motif and polybasic furin cleavage site of Spike in over 70,000 patients revealed that population sweeps of canonical variants of concern (VOCs) occurred in repeating wavelets. Furthermore, we found that subvariants and putative quasi-species with alterations characteristic of future VOCs and/or predicted to be functionally important arose frequently, but always extinguished. Systematic screening of functionally relevant domains in pathogens could thus provide a powerful tool for monitoring spread and mutational trajectories, particularly those with zoonotic potential.

ORGANISM(S): Severe acute respiratory syndrome coronavirus 2 synthetic construct Homo sapiens

PROVIDER: GSE231415 | GEO | 2024/07/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Systematic surveillance of SARS-CoV-2 reveals dynamics of variant mutagenesis and transmission in a large urban population I

Project description:Highly mutable pathogens generate viral diversity that impacts virulence, transmissibility, treatment, and thwarts acquired immunity. We previously described C19-SPAR-Seq, a high-throughput, next-generation sequencing platform to detect SARS-CoV-2 that we deployed to systematically profile variant dynamics of SARS-CoV-2 for over 3 years in a large, North American urban environment (Toronto, Canada). Sequencing of the ACE2 receptor binding motif and polybasic furin cleavage site of Spike in over 70,000 patients revealed that population sweeps of canonical variants of concern (VOCs) occurred in repeating wavelets. Furthermore, we found that subvariants and putative quasi-species with alterations characteristic of future VOCs and/or predicted to be functionally important arose frequently, but always extinguished. Systematic screening of functionally relevant domains in pathogens could thus provide a powerful tool for monitoring spread and mutational trajectories, particularly those with zoonotic potential.

2024-07-30 | GSE224951 | GEO

Systematic surveillance of SARS-CoV-2 reveals dynamics of variant mutagenesis and transmission in a large urban population III

2024-07-30 | GSE246819 | GEO

A Multiplexed, Next-Generation Sequencing Platform for High-Throughput Detection of SARS-CoV-2 [extended cohort]

Project description:Population scale sweeps of viral pathogens, such as SARS-CoV-2, require high intensity testing for effective management. However, reliable systems affording parallel testing of thousands of patients for pathogen infection have not yet been routinely employed. Here we describe “Systematic Parallel Analysis of RNA coupled to Sequencing for Covid-19 screening” (C19-SPAR-Seq), a multiplexed, readily automated platform for SARS-CoV-2 detection capable of analyzing tens of thousands of patient samples in a single instrument run. To address strict requirements for control of assay parameters and output demanded by clinical diagnostics, we employed a control-based Precision-Recall and Receiver Operator Characteristics (coPR) analysis to assign run-specific quality control metrics. C19-SPAR-Seq coupled to coPR on a trial cohort of several hundred patients performed with a specificity of 100% and sensitivity of 91% on samples with low viral loads. Our study thus establishes the feasibility of employing C19-SPAR-Seq for the large-scale monitoring of SARS-CoV-2 and other pathogens.

2021-01-24 | GSE160034 | GEO

A Multiplexed, Next-Generation Sequencing Platform for High-Throughput Detection of SARS-CoV-2 [pilot cohort]

2021-01-24 | GSE160033 | GEO

A Multiplexed, Next-Generation Sequencing Platform for High-Throughput Detection of SARS-CoV-2 [test cohort]

2021-01-24 | GSE160032 | GEO

A Multiplexed, Next-Generation Sequencing Platform for High-Throughput Detection of SARS-CoV-2 [PoC cohort]

2021-01-24 | GSE160031 | GEO

Mucosal Boosting Enhances Vaccine Protection Against SARS-CoV-2 in Rhesus Macaques

Project description:A major limitation of current SARS-CoV-2 vaccines is that they provide minimal protection against acquisition of infection with current Omicron subvariants, although they still provide protection against severe disease. It has been hypothesized that enhanced mucosal immunity will be required to block infection and onward transmission. Intranasal administration of current vaccines has proven inconsistent, suggesting that alternative immunization strategies may be required. Here we show that intratracheal boosting with a bivalent Ad26 based SARS-CoV-2 vaccine results in substantial induction of mucosal humoral and cellular immunity and near complete protection against SARS-CoV-2 BQ.1.1 challenge.

2024-02-14 | GSE245040 | GEO

RNA-seq time-course of Calu-3 cells infected with SARS-CoV-2 early-lineage and Alpha variant viruses

Project description:Emergence of SARS-CoV-2 variants of concern (VOCs), including the globally successful Alpha (B.1.1.7) variant, suggests viral adaptation to enhance human-to-human transmission. Although much effort has focused on characterisation of spike changes, Alpha mutations outside spike likely contribute to adaptation. Here we used RNAseq as well as viral replication assays to show that Alpha isolates more effectively suppress innate immune responses (ISGs as assessed by RNA) in airway epithelial cells, compared to first wave isolates. We found that Alpha has dramatically increased subgenomic RNA and protein levels of N, Orf9b and Orf6, all known innate immune antagonists.

2021-12-31 | E-MTAB-11275 | biostudies-arrayexpress

CRISPR screens for host factors critical for infection by SARS-CoV-2 variants of concern

Project description:The global spread of SARS-CoV-2 lead to the most challenging pandemic in this century, posing major economic and health challenges worldwide. Revealing host genes essential for infection by multiple variants of SARS-CoV-2 can provide insights into the virus pathogenesis, and facilitates the development of novel broad-spectrum host-directed therapeutics. Here, employing genome-scale CRISPR screens, we provide a comprehensive data-set of cellular factors that are exploited by WT-SARS-CoV-2 as well as two additional recently emerged variants of concerns (VOCs), Alpha and Beta. These screens identified known and novel host factors critical for SARS-CoV-2 infection, including various components belonging to the Clathrin-dependent transport pathway, ubiquitination and Heparan sulfate biogenesis. In addition, the host phosphatidylglycerol biosynthesis processes appeared to have major anti-viral functions. Comparative analysis of the different VOCs revealed the host factors KREMEN2 and SETDB1 as potential unique candidates required only to the Alpha variant, providing a possible explanation for the increased infectivity of this variant. Furthermore, the analysis identified GATA6, a zinc finger transcription factor, as an essential pro-viral gene for all variants inspected. We revealed that GATA6 directly regulates ACE2 transcription and accordingly, is critical for SARS-CoV-2 cell entry. Analysis of clinical samples collected from SARS-CoV-2 infected individuals showed an elevated level of GATA6, indicating the important role GATA6 may be playing in COVID-19 pathogenesis. Finally, pharmacological inhibition of GATA6 resulted in down-modulation of ACE2 and consequently to inhibition of the viral infectivity. Overall, we show GATA6 represents a target for the development of anti-SARS-CoV-2 therapeutic strategies and reaffirm the value of the CRISPR loss-of-function screens in providing a list of potential new targets for therapeutic interventions.

2022-03-27 | GSE197962 | GEO

The PDZ-binding motif of SARS-CoV envelope protein is a determinant of viral pathogenesis

Project description:A recombinant SARS-CoV lacking the envelope (E) protein is attenuated in vivo. Here we report that E protein PDZ-binding motif (PBM), a domain involved in protein-protein interactions, is a major virulence determinant in vivo. Elimination of SARS-CoV E protein PBM by using reverse genetics led to attenuated viruses (SARS-CoV-mutPBM) and to a reduction in the deleterious exacerbate immune response triggered during infection with the parental virus (SARS-CoV-wt). Cellular protein syntenin bound E protein PBM during SARS-CoV infection. Syntenin activates p38 MAPK leading to overexpression of inflammatory cytokines, and we have shown that active p38 MAPK was reduced in lungs of mice infected with SARS-CoVs lacking E protein PBM (SARS-CoV-mutPBM) as compared with the parental virus (SARS-CoV-wt), leading to a decreased expression of inflammatory cytokines and to viral attenuation. Therefore, E protein PBM is a virulence factor that activates pathogenic immune response most likely by using syntenin as a mediator of p38 MAPK induced inflammation. Three biological replicates were independently hybridized (one channel per slide) for each sample type (SARS-CoV-wt, SARS-CoV-mutPBM, Mock). Slides were Sure Print G3 Agilent 8x60K Mouse (G4852A-028005)

2014-10-31 | E-GEOD-52920 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data