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Status |
Public on Dec 07, 2020 |
Title |
AI-guided Discovery of a Paradoxical Immune Response in Fatal COVID-19 (Hamster) |
Organism |
Mesocricetus auratus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
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.
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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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Contributor(s) |
Sahoo D, Das S, Ghosh P |
Citation(s) |
32995790, 34127431 |
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Submission date |
Aug 28, 2020 |
Last update date |
Jul 15, 2021 |
Contact name |
Debashis Sahoo |
E-mail(s) |
dsahoo@ucsd.edu
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Phone |
6508624736
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Organization name |
UCSD
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Department |
Pediatrics
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Lab |
Boolean
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Street address |
9500 Gillman Drive
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City |
La Jolla |
State/province |
California |
ZIP/Postal code |
92093 |
Country |
USA |
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Platforms (1) |
GPL28997 |
Illumina NovaSeq 6000 (Mesocricetus auratus) |
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Samples (8)
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Relations |
BioProject |
PRJNA659996 |
SRA |
SRP279209 |
Supplementary file |
Size |
Download |
File type/resource |
GSE157058_Ham-tpm-cov-expr.txt.gz |
1.4 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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