Discovery of key regulators in classical monocyte phenotypes linked to COVID-19 severity using single-cell multi-omics sequencing

Donggun Kim; Sin Young Choi; Chae Yeon Kim; Jeong Rae Yoo; Eui Tae Kim; Jihwan Park

Sin Donggun Kim, Sin Young Choi, Jeong Chae Yeon Kim, Jeong Rae Yoo, Eui Tae Kim, Jihwan Park

iScience, doi:10.1016/j.isci.2026.114849

severity-associated subtypes (IL7R+ cMono and CD163+ cMono) are identified • In IL7R+ cMono, ETS1 drives T cell-like signaling and immune suppressive programs

AUTHOR CONTRIBUTIONS This study was designed by J.P. and E.T.K.; J.R.Y. collected PBMCs from COVID-19 patients.; S.Y.C. performed the single-cell multi-omics sequencing library construction.; Data analysis was performed by D.K.; J.P. guided the process of data analysis.; C.Y.K. performed the experiments under the supervision of E.K.; J.P. and D.K. wrote the original draft of the manuscript. All authors read and approved the final manuscript. DECLARATION OF INTERESTS S.Y.C. is an employee of Eyeoncell, and J.P. holds a leadership position at Eyeoncell. DECLARATION OF GENERATIVE AI AND AI-ASSISTED TECHNOLOGIES IN THE WRITING PROCESS No generative AI or AI-assisted technologies were used in the writing or preparation of this manuscript. STAR★METHODS Detailed methods are provided in the online version of this paper and include the following: • METHOD DETAILS ○ Preparation of human peripheral blood mononuclear cells (PBMCs) from COVID-19 patients ○ Single-cell multi-omics library preparation ○ Preprocessing of single-cell multi-omics data and quality check for obtaining high-quality cells ○ Demultiplexing of donors using genetic variants and doublet filtering ○ Dimension reduction and batch effect correction ○ Peak calling ○ Cell type and RNA-ATAC correlation ○ Differential abundance analysis of KNN graph in COVID-19 infection ○ Gene ontology term and module score analysis ○ Cell-cell interaction analysis using CellphoneDB ○ Gene set enrichment analysis ○ Genomic annotation..

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