Human Genome Polymorphisms and Computational Intelligence Approach Revealed a Complex Genomic Signature for COVID-19 Severity in Brazilian Patients

Viruses. 2023 Feb 28;15(3):645. doi: 10.3390/v15030645.

Abstract

We present a genome polymorphisms/machine learning approach for severe COVID-19 prognosis. Ninety-six Brazilian severe COVID-19 patients and controls were genotyped for 296 innate immunity loci. Our model used a feature selection algorithm, namely recursive feature elimination coupled with a support vector machine, to find the optimal loci classification subset, followed by a support vector machine with the linear kernel (SVM-LK) to classify patients into the severe COVID-19 group. The best features that were selected by the SVM-RFE method included 12 SNPs in 12 genes: PD-L1, PD-L2, IL10RA, JAK2, STAT1, IFIT1, IFIH1, DC-SIGNR, IFNB1, IRAK4, IRF1, and IL10. During the COVID-19 prognosis step by SVM-LK, the metrics were: 85% accuracy, 80% sensitivity, and 90% specificity. In comparison, univariate analysis under the 12 selected SNPs showed some highlights for individual variant alleles that represented risk (PD-L1 and IFIT1) or protection (JAK2 and IFIH1). Variant genotypes carrying risk effects were represented by PD-L2 and IFIT1 genes. The proposed complex classification method can be used to identify individuals who are at a high risk of developing severe COVID-19 outcomes even in uninfected conditions, which is a disruptive concept in COVID-19 prognosis. Our results suggest that the genetic context is an important factor in the development of severe COVID-19.

Keywords: COVID-19 genetics; SARS-CoV-2 infection; complex genomic classifier; machine learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Artificial Intelligence
  • B7-H1 Antigen
  • Brazil / epidemiology
  • COVID-19* / diagnosis
  • COVID-19* / genetics
  • Genome, Human*
  • Genomics
  • Humans
  • Interferon-Induced Helicase, IFIH1

Substances

  • B7-H1 Antigen
  • Interferon-Induced Helicase, IFIH1

Grants and funding

We thank FIOTEC Foundation (FIOCRUZ) for the financial support of this study by means of the grants n° VPPCB-005-FIO-20-2-14, VPPCB-005-FIO-20-2-57.