Fig. 2: Deriving and validating a composite blood assay signature of pain-associated conditions.
From: Biological markers and psychosocial factors predict chronic pain conditions
a, A schematic of the composite signature’s development for 13 pain-related diagnoses, plus a timeline of UK Biobank data points used. b, The diagnostic and prognostic efficacy of the signature, assessed by Cohen’s d and ROC-AUC, comparing individuals with and without diagnoses, and those who develop diagnoses versus those remaining diagnosis-free. Diagnostic accuracy is measured at baseline, prognostic accuracy at 4 and 9 years post-baseline. Bars show the mean Cohen’s d from 1,000 bootstrap resamples, with error bars indicating the ±95% CI. Overlaid points are a random subsample (n = 50) of these 1,000 resamples. c, A circular graph depicting the signature’s structure: the outer heat map displays blood marker coefficients; the middle layers show individual diagnosis marker coefficients, numbered as in b; and the inner layer presents the standard deviation of marker coefficients. Each segment corresponds to inflammatory/immune, metabolic or haematological assays. d, Pooled effect sizes from c, measured by Cohen’s d, compare baseline diagnoses or diagnoses developing by 4 or 9 years with diagnosis-free individuals. A two-sided Wilcoxon rank-sum test used to compute P values. e, Temporal changes in the signature for participants with ongoing diagnoses, newly developing diagnoses at 4 or 9 years, or remaining diagnosis-free. The significance of signature change between each group and the Stay Dx-free control group was estimated using two-sided linear mixed-effects models, with adjustments for multiple comparisons using Bonferroni correction (Pongoing = 0.07, P4-yr < 0.001, P9-yr = 0.001; Pbonf. < 0.05). Data are presented as mean ± 95% CI from 1,000 bootstrap resamples. f, A simplified model using the top 10 assays was validated with data from the AoU. g, Its discriminatory power is shown via Cohen’s d and ROC-AUC. Bars indicate the mean from 1,000 bootstraps (±95% CI), with overlaid subsampled points (n = 50). Inflammatory/immune markers: CRP, C-reactive protein; Neut, neutrophil; WBC, white blood cell; Mono, monocyte; Eos, eosinophil; baso, Basophil; Lymph, lymphocyte. Metabolic markers: GGT, gamma glutamyl transferase; Cys C, cystatin C; TG, triglyceride; ALP, alkaline phosphatase; UA, uric acid; HbA1c, glycated haemoglobin, Glu, glucose; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Cr, creatinine; TP, total protein; Testo, testosterone; Ca, calcium; ApoB, apolipoprotein b; TBil, total bilirubin; IGF1, insulin-like growth factor; LDL-C, low-density lipoprotein cholesterol; Alb, albumin; TC, total cholesterol. Haematological markers: HLR, high light scatter reticulocyte percentage; Retic, reticulocyte; IRF, immature reticulocyte fraction; RDW, red blood cell distribution width; PCT, platelet count; PLT, platelet count; PDW, platelet distribution width; nRBC; nucleated red blood cell; SCV, sphered cell volume; MPV, mean platelet volume; Hct, haematocrit; Hgb, haemoglobin; Dx, diagnosis; UKBB, UK Biobank; nos, not otherwise specified; Dist., distribution.
