Fig. 5: Spatial multi-omic analysis of macrophages in patients with COVID-19.

a, Schematic of the experimental and MARIO analysis on BALF and lung tissues from patients with COVID-19 were measured from two independent studies via CITE-seq (from VIB/Ghent) and CODEX (University Hospital Basel/Stanford). Macrophages from the CODEX were matched to those in CITE-seq. b, Heatmaps of C1Q high and low macrophages identified from CITE-seq, and their matched CITE-seq and CODEX expression patterns. c, A ranked plot (median ± 1.5 IQR) for macrophages from each patient (n = 23) in the CODEX data, as a percentage of C1Q high proportions. d, Proportion of neutrophils (of all cell types) in each patient from the CODEX data, ranked by the same sequence as in c (P value and correlation calculated by a two-sided Spearman-ranked test). e, A dot plot with 95% CI showing the relationship between C1Q high macrophages (y axis) and neutrophil percentage (x axis). Each dot represents a tissue core (n = 76). Colors represent patients. f, A representative pseudo image of two tissue cores colored with the locations of C1Q high and low macrophages. g, The CODEX images of the same two tissue cores in f, with CD163, CD68 and CD15 antibody staining. Scale bars, 400 μm (left) and 100 μm (right). h, An experimental schematic of PANINI to validate the spatial localization of C1Q macrophages on Basel/Stanford COVID-19 tissues. Slides were costained with probes detecting C1QA mRNA and antibodies targeting CD15 and CD68 proteins. i,j, A dot plot with 95% CI showing the relationship between the proportion of C1QA high macrophages (to all macrophages) from the PANINI validation (y axis) versus the MARIO prediction (x axis) per patient (i) or per tissue core (j). P values and correlations were calculated using a two-sided Spearman-ranked test. k, Anchor plots of neutrophils as a function of distance from C1QA high or low macrophages in MARIO-predicted (above) or PANINI-validated (below) experiments. l,m, A representative tissue core with MARIO-predicted C1QA expression levels in macrophages (left), and PANINI-validated C1QA and CD68 signals (right). Scale bar, 400 μm. n, Dot plot with 95% CI of spatial-correlations of C1QA between validation and prediction experiments (P value and correlation calculated by a two-sided Spearman-ranked test). Each dot represents a region in the core.