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Multi-objective optimization identifies a specific and interpretable COVID-19 host response signature
- Source :
- Cell systems. 13(12)
- Publication Year :
- 2022
-
Abstract
- The identification of a COVID-19 host response signature in blood can increase the understanding of SARS-CoV-2 pathogenesis and improve diagnostic tools. Applying a multi-objective optimization framework to both massive public and new multi-omics data, we identified a COVID-19 signature regulated at both transcriptional and epigenetic levels. We validated the signature's robustness in multiple independent COVID-19 cohorts. Using public data from 8,630 subjects and 53 conditions, we demonstrated no cross-reactivity with other viral and bacterial infections, COVID-19 comorbidities, or confounders. In contrast, previously reported COVID-19 signatures were associated with significant cross-reactivity. The signature's interpretation, based on cell-type deconvolution and single-cell data analysis, revealed prominent yet complementary roles for plasmablasts and memory T cells. Although the signal from plasmablasts mediated COVID-19 detection, the signal from memory T cells controlled against cross-reactivity with other viral infections. This framework identified a robust, interpretable COVID-19 signature and is broadly applicable in other disease contexts. A record of this paper's transparent peer review process is included in the supplemental information.
Details
- ISSN :
- 24054720
- Volume :
- 13
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Cell systems
- Accession number :
- edsair.doi.dedup.....1e21658624e8f722018ff44379e76064