Fig. 3: Performance of ViP/sViP signatures on independent MIS-C datasets and on diverse tissues and in diverse diseases of the immune system.

a–c Severe (s)ViP signature can classify severe MIS-C based on in two independent studies (GSE166489¹⁵ and GSE167028³⁸). Schematic in a summarizes the definition of severe MIS-C. b, c Classification of blood samples in two cohorts of MIS-C subjects, based on the need for ICU management due to the presence (MYO+) or recovery in the absence (R or MYO−) of myocardial dysfunction using sViP signature. Welch’s two sample unpaired two-sided t-test is performed to compute the p values. d Bubble plots of ROC-AUC values (radii of circles are based on the ROC-AUC) and the direction of gene regulation (Up, red; Down, blue) in publicly available datasets using 4 gene signatures: the 166-gene ViP signature, the 20-gene sViP signature, the KD-13 signature, and finally the IL15/IL15RA composite score. Numbers on top of bubble plots indicate number (n) of control vs. disease samples in each dataset. Abbreviations: PBMCs peripheral blood mononuclear cells, Mac macrophages, WB whole blood, MTb M. tubercutosis, Flu Influenza, HIV human immunodeficiency virus, RSV respiratory syncytial virus, JM juvenile myositis, sjia systemic juvenile idiopathic arthritis, SLE systemic lupus erythematosus, IBD Inflammatory bowel disease, COPD chronic obstructive pulmonary disesase, JDM juvenile dermatomyositis, MS multiple sclerosis, BAL bronchoalveolar lavage, NOMID neonatal onset multisystem inflammatory disease, MAS macrophage activation syndrome, NLRC4 NLR Family CARD Domain Containing 4. e Schematic showing the experimental design for studying differentially expressed genes (DEGs) in between KD and MIS-C subjects. f, g PCA (f) and a clustered heatmap analysis (g) of KD (green, f) and MIS-C (orange, f) samples are shown based on top 2242 genes according to mean absolute deviation identified using StepMiner algorithm⁸⁸. Source data are provided. h Reactome pathway analysis of the DEGs between seven KD and seven MIS-C subjects in f (marked on the PCA). i Venn diagram between 166-gene ViP signature against the DEGs. Number of genes are indicated for each group in the Venn diagram. 11 overlapping genes between ViP signature and up-regulated in MIS-C are listed at the top.