Fig. 2: Identification of a pan-organ rejection signal across solid organ transplantation.

a, Venn diagram showing the overlap and uniqueness of differentially expressed genes between biopsy samples from allografts experiencing acute rejection and otherwise stably functioning grafts. The number of overlapping genes (and number of genes expected by chance). b, Heatmap of the top 50 rejection-specific genes, with each column representing a dataset and each row a gene. c, Box plot of Cepo enrichment scores of genes from b in cell types from acute rejection and stably functioning grafts (n = 6 and n = 16 biologically independent control and allograft rejection (AR) samples were used, respectively). d, t-SNE plot of merged single-cell RNA-seq datasets, with cells colored by cell type classification. e, t-SNE plot of merged single-cell RNA-seq datasets, with cells colored by average expression of genes from b. f, Violin plot depicting the expression of rejection markers across minor cell types. The x axis represents different cell types, and the y axis represents the average expression of the rejection gene set markers from b. The width of each violin plot corresponds to the density of expression values for each cell type. g, Box plot of liquid biopsy dataset model performance measured by AUC, comparing the performance of organ-specific models from heart (n = 3 datasets from 65 biologically independent patient samples), kidney (n = 18 datasets from 2,257 biologically independent patient samples) and liver (n = 2 datasets from 100 biologically independent patient samples) compared to the pan-organ model (n = 23 datasets from 2,422 biologically independent patient samples). Each point is an evaluation of model performance on an independent dataset. Points that are joined by a line represent the same dataset. h, ROC plot of three models applied to AUSCAD: Pan-Organ model (trained on all peripheral blood datasets in PROMAD), Kidney-specific model (trained on all kidney transplant peripheral blood datasets in PROMAD) and Clinical model (creatinine, eGFR and serum albumin). Each model was evaluated using the AUC. Box plots in c and g show Q1, median and Q3, and the lower and upper whiskers show Q1 − 1.5× IQR and Q3 + 1.5× IQR, respectively. AT, alveolar type; ILC, innate lymphoid Cell; IQR, interquartile range; NK, natural killer; Q, quartile.