Figure 4

CITRUS identifies differentially abundant immune cell subsets between PBC patients and age-/sex-matched controls. (A) CITRUS produces a radial hierarchical tree of cells subsets using an unsupervised clustering approach. Each node (i.e., cluster) represents a subset of cells, and each edge points from a parent node to child node(s). Only the highlighted nodes correspond to cell subsets of statistically significant differential abundance using a significance analysis of microarray (SAM) correlative association model (Benjamini–Hochberg adjusted p value < 0.05). (E) CITRUS map shows a significantly higher abundance of CD14⁺CD11c⁺CD66b⁺ cells, and lower abundances of CD19⁺CD24^hiCD27⁺ and CD3⁺CD8⁺CD161⁺ cells, in PBC compared to control. CITRUS maps overlaid with marker-specific intensities show their relative expression levels (across all nodes) in the proposed (B) CD19⁺CD24^hiCD27⁺; (C) CD14⁺CD11c⁺CD66b⁺; and (D) CD3⁺CD8⁺CD161⁺ cell subsets. The nodes circled in black indicate positive or high expression of a particular marker.