Fig. 5: Type-B UPV signature separates adults and children into distinct phenotypic and metabolic sub-types.
From: Independent phenotypic plasticity axes define distinct obesity sub-types
a, Heat map of k-means clustering of TwinsUK individuals. Four clusters were generated according to expression of the UPV-B signature. The UPV-B ranks annotation show the median rank of everyone according to their level of expression of UPV-B signature genes, discriminating Type-B ‘heavy-like’ and ‘light-like’ individuals. The obesity annotation is based on arbitrary cutoffs of BMI (obesity, >30 BMI; severe obesity, >35 BMI). The average expression of HDAC-signature (HDAC-sig) genes (leading-edge genes from Extended Data Fig. 6d) is reported. a′, Heat map (bottom), the expression profile of the most variable genes (top 1,000) across all samples is reported, after k-means clustering into five gene sets. Venn plot (left) shows the overlap between the most variable genes and the UPV-B. b–b′, Same as in a–a′, but on the LCAT cohort. The obesity annotation is based on standardized BMI arbitrary cutoffs (BMI standard score (SDS), obesity >1.88). On the right, representative results from Gene Ontology (GO) and pathway enrichment analysis for the five gene sets from the heat map of the TwinsUK individuals (a′). GO, KEGG and Molecular Signatures Database (MSigDB) databases were assessed. Related to the extended analysis in Extended Data Fig. 8g. c–f, Box-plots showing the distributions of indicated gene expression profiles (c), normalized DNA methylation on UPV-B DMRs (d), metabolic traits (e) and morphometric measurements (f), between Type-A and Type-B obesities (TwinsUK individuals affected by obesity and belonging to clusters 3 and 4 (cl.3 and 4) from the heat map in a). *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, NS, not significant, as assessed by two-tailed Student’s t-tests. NNAT P = 0.00036; IGN1 P value = 0.0067; HDAC P = 2.2 × 10–16; UPV-B DMRs ‘heavy’ P = 0.028; UPV-B DMRs ‘light’ P = 0.00026; insulin P = 0.001; height P = 0.4; BMI P = 0.21; FatMI P = 0.46; LeanMI P = 0.047. In all box-plots, the lower and upper hinges indicate 25th and 75th percentiles. The upper/lower whiskers indicate largest/smallest observation less/greater than upper/lower hinge + 1.5 × IQR. Central median indicates 50% quantile. GSH, glutathione; MHC, major histocompatibility; IFN, interferon; T1D, type 1 diabetes.
