Gene Expression
Nebulas
Gene Expression NebulasSummary: We sought to define the host immune response, a.k.a, the “cytokine storm” that has been implicated in fatal COVID-19 using an AI-based approach. Over 45,000 publicly available transcriptomic datasets of viral pandemics were analyzed to extract a 166-gene signature using ACE2 as a ‘seed’ gene; ACE2 was rationalized because the receptor it encodes enables the virus that causes Covid-19, SARS-CoV-2, to enter host cells. The signature was surprisingly conserved in all viral pandemics, including COVID-19, inspiring the nomenclature ViP-signature. A subset of 20-genes classified disease severity in respiratory pandemics. The ViP signatures pinpointed airway epithelial and myeloid cells as the major contributors of an IL-15 cytokine storm, and epithelial and NK cell destruction as determinants of severity/fatality. They also helped formulate precise therapeutic goals to reduce disease symptoms and severity. Thus, the ViP signatures provide a quantitative and qualitative framework for titrating the immune response in viral pandemics and may serve as a powerful unbiased tool in our armamentarium to rapidly assess disease severity and vet candidate drugs
Overall Design: Lung samples from 8-week old Syrian hamsters were used from a previously published study (PMID:32540903). We chose three different groups of samples: uninfected control, SARS-CoV-2 challenge after Den3 (antibody to dengue virus), and SARS-CoV-2 challenge after Anti-CoV2 (CC12.2; a potent SARS-CoV-2 neutralizing antibodies) (PMID:32540903)
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| Growth Protocol: | Hamster lung samples were collected from previously published study |
| Treatment Protocol: | Hamster were infected with SARS-CoV-2 using a BSL-3 facility.; Hamster were infected with SARS-CoV-2 using a BSL-4 facility.; Hamster were infected with SARS-CoV-2 using a BSL-5 facility.; Hamster were infected with SARS-CoV-2 using a BSL-6 facility.; Hamster were infected with SARS-CoV-2 using a BSL-7 facility.; Hamster were infected with SARS-CoV-2 using a BSL-8 facility.; Hamster were infected with SARS-CoV-2 using a BSL-9 facility.; Hamster were infected with SARS-CoV-2 using a BSL-10 facility. |
| Extract Protocol: | RNA were extracted after infection using the Quick-RNA MicroPrep Kit (Zymo Research, USA) according to the manufacture’s instruction. RNA was converted into cDNA using the qScript™ cDNA SuperMix (Quantabio). |
| Library Construction Protocol: | RNA sequencing libraries were generated using the Illumina TruSeq Stranded Total RNA Library Prep Gold with TruSeq Unique Dual Indexes (Illumina, San Diego, CA). |
| Molecule Type: | Total RNA |
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| Library Layout: | PAIRED |
| Library Strand: | Forward |
| Platform: | ILLUMINA |
| Instrument Model: | Illumina NovaSeq 6000 |
| Strand-Specific: | Specific |
| Data Resource | GEN Sample ID | GEN Dataset ID | Project ID | BioProject ID | Sample ID | Sample Name | BioSample ID | Sample Accession | Experiment Accession | Release Date | Submission Date | Update Date | Species | Race | Ethnicity | Age | Age Unit | Gender | Source Name | Tissue | Cell Type | Cell Subtype | Cell Line | Disease | Disease State | Development Stage | Mutation | Phenotype | Case Detail | Control Detail | Growth Protocol | Treatment Protocol | Extract Protocol | Library Construction Protocol | Molecule Type | Library Layout | Strand-Specific | Library Strand | Spike-In | Strategy | Platform | Instrument Model | Cell Number | Reads Number | Gbases | AvgSpotLen1 | AvgSpotLen2 | Uniq Mapping Rate | Multiple Mapping Rate | Coverage Rate |
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