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Altered and allele-specific open chromatin landscape reveals epigenetic and genetic regulators of innate immunity in COVID-19.
Zhang, Bowen; Zhang, Zhenhua; Koeken, Valerie A C M; Kumar, Saumya; Aillaud, Michelle; Tsay, Hsin-Chieh; Liu, Zhaoli; Kraft, Anke R M; Soon, Chai Fen; Odak, Ivan; Bosnjak, Berislav; Vlot, Anna; Swertz, Morris A; Ohler, Uwe; Geffers, Robert; Illig, Thomas; Huehn, Jochen; Saliba, Antoine-Emmanuel; Sander, Leif Erik; Förster, Reinhold; Xu, Cheng-Jian; Cornberg, Markus; Schulte, Leon N; Li, Yang.
  • Zhang B; Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Zhang Z; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Koeken VACM; Beijing Normal University, College of Life Sciences, Beijing, China.
  • Kumar S; Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Aillaud M; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Tsay HC; Genomics Coordination Center, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands.
  • Liu Z; Department of Genetics, University of Groningen and University Medical Center Groningen, the Netherlands.
  • Kraft ARM; Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Soon CF; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Odak I; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands.
  • Bosnjak B; Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Vlot A; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Swertz MA; Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Ohler U; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Geffers R; Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Illig T; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Huehn J; Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Saliba AE; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Sander LE; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
  • Förster R; German Centre for Infection Research (Deutsches Zentrum für Infektionsforschung DZIF), Partner Site Hannover-Braunschweig, Hannover, Germany.
  • Xu CJ; Cluster of Excellence Resolving Infection Susceptibility (RESIST; EXC 2155), Hannover Medical School, Hannover, Germany.
  • Cornberg M; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Schulte LN; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
  • Li Y; Institute of Immunology, Hannover Medical School, Hannover, Germany.
Cell Genom ; : 100232, 2022 Dec 02.
Article in English | MEDLINE | ID: covidwho-2237461
ABSTRACT
SARS-CoV-2 infection causes severe COVID-19 in some patients and mild in others. Dysfunctional innate immune responses have been identified to contribute to COVID-19 severity, but the key regulators are still unknown. Here, we present an integrative single-cell multi-omics analysis of peripheral blood mononuclear cells from hospitalized and convalescent COVID-19 patients. In classical monocytes, we identified genes that were potentially regulated by differential chromatin accessibility. Then, sub-clustering and motif-enrichment analyses reveals disease condition-specific regulation by transcription factors and their targets, including an interaction between C/EBPs and a long-noncoding RNA LUCAT1, which we validated through loss-of-function experiments. Finally, we investigated genetic risk variants that exhibit allele-specific open chromatin (AsoC) in COVID-19 patients and identified a SNP rs6800484-C, which is associated with lower expression of CCR2 and may contribute to higher viral loads and higher risk of COVID-19 hospitalization. Altogether, our study highlights the diverse genetic and epigenetic regulators that contribute to COVID-19.

Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Variants Language: English Journal: Cell Genom Year: 2022 Document Type: Article Affiliation country: J.xgen.2022.100232

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Variants Language: English Journal: Cell Genom Year: 2022 Document Type: Article Affiliation country: J.xgen.2022.100232