概要: 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
项目整体设计: 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)
Hamster lung samples were collected from previously published study
处理方案:
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.
提取方案:
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).
建库方案:
RNA sequencing libraries were generated using the Illumina TruSeq Stranded Total RNA Library Prep Gold with TruSeq Unique Dual Indexes (Illumina, San Diego, CA).
测序信息
分子类型:
Total RNA
库的片段类型:
PAIRED
库的链类型:
Forward
测序平台:
ILLUMINA
测序仪型号:
Illumina NovaSeq 6000
链特异性:
Specific
样本
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疾病
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唯一比对率
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覆盖度
文章
AI-guided discovery of the invariant host response to viral pandemics.
bioRxiv : the preprint server for biology . 2021-04-13 [PMID:
32995790]
AI-guided discovery of the invariant host response to viral pandemics.