Manchester Centre for Genomic Medicine (MANGEN): against COVID-19. Hub
Project: Covid Host Genetics Study (COHGEN)
The **primary objective **is to assess whether individual genetic variation is associated with COVID-19 disease severity. The **secondary objectives **are to assess underlying variation on length of hospital stay, need for ventilation, cardiac involvement, renal involvement and need for renal replacement therapy. We will also assess confounding factors which could impact disease severity, a subset of patients will have the SARS-Cov-2 viral genome sequenced via nanopore sequencing to ensure that disease severity is not primarily associated with more virulent underlying strains. Samples will also be assessed for co-infection through metagenome sequencing approaches to ensure that severity is not related to the cumulative impact of multiple viral species.
Study design: We plan to perform paired analyses of viral genome sequences with patient genotyping techniques for patients testing positive for COVID-19. Patients admitted to hospital and testing positive for COVID-19 will be recruited to the ManARTS biobank and we propose that an EDTA blood sample is taken, allowing extraction of DNA for subsequent analysis. This will be performed in parallel with nanopore sequencing of the SARS-Cov-2 viral genome. Bringing together these two pieces of work, in collaboration with international consortia, will allow us to rapidly identify high impact genomic signals which correspond with disease severity. DNA will be extracted from EDTA samples at the MCGM and sorted in our facility as required. This process produces a large quantity of DNA and therefore we would ensure that aliquots are freely available to other academics within the ManARTS collaboration to accelerate their research. We also commit to the open sharing of any data we generate and would make this freely available to academics following a formal request and approval by ManARTS. The outline of each arm of the work is detailed below. Patient Genotyping Patient genotyping will be performed using the Illumina Infinium Omni2.5-8 genotyping SNP chip or similar, and single candidate gene sequencing (e.g. ACE2, HLA, TMPRSS2) will be performed using targeted Sanger sequencing. Genotyping approaches and pooled analysis will be coordinated with the COVID-19
Host Genetics Initiative (https://www.covid19hg.org/).
Initially, Genome Wide Association Studies will be performed to rapidly identify host genomic variants significantly associated with susceptibility and severity. Sanger sequencing datasets will be analysed locally through appropriate software (IGV, SnapGene, Alamut) to visualize genomic variants and to model their impact.
Thereafter, we plan to apply for funding for retrospective WGS and WES data generation as part of the wider consortia to provide a more comprehensive assessment of patient genomic variation and compare these data with those collected through the UK BioBank and Genomics England 100,000 Genomes Project. Viral Genome Sequencing The SARS-CoV-2 genome will be sequenced to a depth of >50 unique sequencing reads covering the complete viral genome. Laboratory and bioinformatics approaches will be performed through a PCR-tiling technique described in the ARCTIC protocol. This data will be shared with the Global Initiative on Sharing All Influenza Data (gisaid.com) for phylogenetic analysis and comparison of viral strains between patients. Variation between viral strains will be identified through appropriate techniques, e.g. variant calling through the Genome Analysis Toolkit and multi-way sequence alignments through ClustalOmega. We will identify any viral genome with one or more difference in viral strain, we will perform in-silico modelling to predict the impact of the variant, and, if appropriate, assess whether specific viral strains are enriched in patients with severe COVID-19. Where possible we will also perform metagenome sequencing from nasopharyngeal swabs to understand if coinfections exist, utilizing the SISPA protocol.
Study Type: Prospective (n=150)
Assays planned: Viral sequencing
Other assays: Viral sequencing of via nanopore
Investigators: Dr John McDermott, Dr Jamie Ellingford
This project is partner of the global consortium "The COVID-19 Host Genetics Initiative".
https://www.covid19hg.org/partners/
The **primary objective **is to assess whether individual genetic variation is associated with COVID-19 disease severity. The **secondary objectives **are to assess underlying variation on length of hospital stay, need for ventilation, cardiac involvement, renal involvement and need for renal replacement therapy. We will also assess confounding factors which could impact disease severity, a subset of patients will have the SARS-Cov-2 viral genome sequenced via nanopore sequencing to ensure that disease severity is not primarily associated with more virulent underlying strains. Samples will also be assessed for co-infection through metagenome sequencing approaches to ensure that severity is not related to the cumulative impact of multiple viral species.
Study design: We plan to perform paired analyses of viral genome sequences with patient genotyping techniques for patients testing positive for COVID-19. Patients admitted to hospital and testing positive for COVID-19 will be recruited to the ManARTS biobank and we propose that an EDTA blood sample is taken, allowing extraction of DNA for subsequent analysis. This will be performed in parallel with nanopore sequencing of the SARS-Cov-2 viral genome. Bringing together these two pieces of work, in collaboration with international consortia, will allow us to rapidly identify high impact genomic signals which correspond with disease severity. DNA will be extracted from EDTA samples at the MCGM and sorted in our facility as required. This process produces a large quantity of DNA and therefore we would ensure that aliquots are freely available to other academics within the ManARTS collaboration to accelerate their research. We also commit to the open sharing of any data we generate and would make this freely available to academics following a formal request and approval by ManARTS. The outline of each arm of the work is detailed below. Patient Genotyping Patient genotyping will be performed using the Illumina Infinium Omni2.5-8 genotyping SNP chip or similar, and single candidate gene sequencing (e.g. ACE2, HLA, TMPRSS2) will be performed using targeted Sanger sequencing. Genotyping approaches and pooled analysis will be coordinated with the COVID-19
Host Genetics Initiative (https://www.covid19hg.org/).
Initially, Genome Wide Association Studies will be performed to rapidly identify host genomic variants significantly associated with susceptibility and severity. Sanger sequencing datasets will be analysed locally through appropriate software (IGV, SnapGene, Alamut) to visualize genomic variants and to model their impact.
Thereafter, we plan to apply for funding for retrospective WGS and WES data generation as part of the wider consortia to provide a more comprehensive assessment of patient genomic variation and compare these data with those collected through the UK BioBank and Genomics England 100,000 Genomes Project. Viral Genome Sequencing The SARS-CoV-2 genome will be sequenced to a depth of >50 unique sequencing reads covering the complete viral genome. Laboratory and bioinformatics approaches will be performed through a PCR-tiling technique described in the ARCTIC protocol. This data will be shared with the Global Initiative on Sharing All Influenza Data (gisaid.com) for phylogenetic analysis and comparison of viral strains between patients. Variation between viral strains will be identified through appropriate techniques, e.g. variant calling through the Genome Analysis Toolkit and multi-way sequence alignments through ClustalOmega. We will identify any viral genome with one or more difference in viral strain, we will perform in-silico modelling to predict the impact of the variant, and, if appropriate, assess whether specific viral strains are enriched in patients with severe COVID-19. Where possible we will also perform metagenome sequencing from nasopharyngeal swabs to understand if coinfections exist, utilizing the SISPA protocol.
Study Type: Prospective (n=150)
Assays planned: Viral sequencing
Other assays: Viral sequencing of via nanopore
Investigators: Dr John McDermott, Dr Jamie Ellingford
This project is partner of the global consortium "The COVID-19 Host Genetics Initiative".
https://www.covid19hg.org/partners/
Technology:
COVID Labs/Universities
Industry:
COVID R&D
Headquarters:
United Kingdom
Founded Date:
N/A
Employees Number:
N/A
Funding Status:
N/A
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