Fig. 4: The PROMAD atlas reveals pan-organ markers for allograft tolerance.

a,b, Heatmaps of the top 20 genes implicated in allograft tolerance, with each column representing a dataset and each row a gene. a corresponds to datasets that sampled PBMCs, and b corresponds to whole blood datasets. c, Box plot of model performance measured by AUC, comparing the performance of organ-specific kidney (n = 2 datasets from 68 biologically independent patient samples) and liver (n = 3 datasets from 52 biologically independent patient samples) models compared to the pan-organ model (n = 5 datasets from 120 biologically independent liver and kidney patient samples). Each point is evaluation of model performance on an independent dataset. Points that are joined by a line represent the same dataset. d, Bar plot of pathways that are enriched for genes differentially expressed in whole blood from tolerant recipients. Gene set enrichment was evaluated using a two-sided Wilcoxon rank-sum test. Each bar represents one Gene Ontology pathway where P values were adjusted for multiple comparisons using Benjamini–Hochberg correction. e, Box plot of predicted early allograft dysfunction risk on a logit scale. Each dataset contained biopsy samples before and after NMP. A two-sided t-test was used to determined significance levels between the groups (***P < 0.001, **P < 0.01 and *P < 0.05). Datasets had a varying number of biologically independent samples before and after NMP, respectively (n = 10, 10, P = 0.006; n = 6, 6, P = 0.041; n = 5, 10, P = 0.114; n = 6, 6, P = 0.157; n = 6, 6, P = 0.008; n = 5, 6, P = 0.793). f, Network plot of model coefficients for predicting DGF. Each line joins the two genes into a ratio, where the weight of the line corresponds to the magnitude of the model coefficients. Lines in red and blue are positive and negative coefficients, respectively. g, Box plot of model performance (AUC) from pre-transplant biopsies in predicting DGF (n = 7 datasets from 279 biologically independent patient samples), acute rejection (n = 3 datasets from 195 biologically independent patient samples) and fibrosis (n = 2 datasets from 124 biologically independent patient samples). Box plots from c, e and g show Q1, median and Q3, and the lower and upper whiskers show Q1 − 1.5× IQR and Q3 + 1.5× IQR, respectively. IQR, interquartile range; PreTx, pretransplantation; Q, quartile.