Fig. 5: Global changes in gene and gene product expression in the blood of individuals with LC.

a, Relative expression of OR7D2 and ALAS2 as determined by bulk RNA-seq analysis of whole blood from LC versus R individuals. *P < 0.05 (two-sided Wald test, Benjamini–Hochberg correction). Purple asterisks identify the female donors selected for scRNA-seq analyses. Horizontal bars indicate mean, error bars indicate s.d. and dots represent individuals. LC (n = 23) and R (n = 13). b, Heatmap of the top 50 DEGs in LC versus R individuals based on clustering analysis of bulk RNA-seq data. Genes are grouped into k clusters based on similarity. c, Network mapping of DEGs from bulk RNA-seq analysis. Each node corresponds to a gene; colors of nodes indicate the extent of change; red indicates upregulation and blue indicates downregulation in LC compared to R. Edges depict the functional relevance between pairs of genes, where thickness corresponds to confidence of evidence. d, UMAP of clusters of all LC and R PBMCs analyzed by scRNA-seq. LC (n = 8) and R (n = 4). e, Relative expression of THEMIS and NUDT2 in CD8⁺ T cell cluster 1 and PPIE in monocyte cluster 3 in LC versus R individuals as determined by scRNA-seq analysis. *P < 0.05 (two-sided empirical Bayes quasi-likelihood F tests, with Benjamini–Hochberg correction). Horizontal bars indicate mean, error bars indicate s.d. and dots represent individuals. LC (n = 8) and R (n = 4). f, Volcano plots depicting DEGs in LC versus R individuals in scRNA-seq-defined clusters. DEGs with P < 0.1 (two-sided empirical Bayes quasi-likelihood F tests, Benjamini–Hochberg correction) are labeled. The x axes represent the log₂(fold change) of the mean expression of each gene between the comparison groups, and the y axes represent the raw −log₁₀(P values). Dashed horizontal lines delineate thresholds corresponding to Benjamini–Hochberg adjusted P values of <0.1. g, Clustered heatmap of the top 25 differentially expressed proteins from Olink analysis performed on plasma of LC and R individuals with markers grouped into k-means clusters based on similarity. LC (n = 25) and R (n = 15). h, Network mapping of related differentially expressed proteins as detected by Olink. Graph representations as in c.