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Fig. 4 | Genome Medicine

Fig. 4

From: A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases

Fig. 4

Diagnostic potential of CD4+ T cells based on clinical profiling studies of 13 diseases. a Toy model of a disease module. Disease-associated genes (red) are mapped on proteins (blue) in the human protein-protein interaction network. Disease-associated genes that co-localize form a module. b Overview of the module-based analyses. First step is the identification of disease modules for each of the 13 diseases profiled in the prospective microarray study of CD4+ T cells. For each disease module, genes separate patients from healthy controls. For pairwise comparison of the diseases, genes in the union of two respective modules separate patients with different diseases; for example, genes in influenza and asthma modules separate patients with influenza from patients suffering from asthma with AUC of 0.99, p = 3.3 × 10−5, as shown in c. c Heatmap presenting area under the curve (AUC) values of 13 disease classifications based on the module intersections genes, using elastic net. d An independent validation study of classification accuracy of breast cancer patients (n = 24) and healthy subjects (n = 14) based on previously preselected biomarkers (genes) measured in CD4+ T cells. Classification was performed with elastic net, preserving same lambda (λ) value as estimated for the original study. ej Potential diagnostic classification of IBD patients based on six secreted plasma proteins identified in the intersection of ulcerative colitis (UC) and Crohn’s disease (CD) modules. These proteins could separate patients from healthy controls (HCs). e CXCL11; f CCL25; g CXCL1; h CXCL8; i IL1B; j TNF. k Crohn’s disease and ulcerative colitis patients’ classification based on normalized protein levels of CXCL1 and CXCL8. UC, ulcerative colitis; CD, Crohn disease; HC, healthy controls. Star denotes p value < 0.05. dk The bars in the boxes represent median and 25th and 75th percentiles, while whiskers extend to ± 2.7σ (see the “Methods” section)

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