Figures and data
Web tool overview and inter-individual correlation structure of established endocrine proteins.
A, Web server structure for user-defined interactions, as well as server and shiny app implementation scheme for GD-CAT. B, All genes across the 18 metabolic tissues in 310 individuals were correlated with expression of ADIPOQ in subcutaneous adipose tissue, where a qvalue cutoff of q<0.1 showed the strongest enrichments with subcutaneous and muscle gene expression (pie chart, left). Gene set enrichment analysis (GSEA) was performed using the bicor coefficient of all genes to ADIPOQ using gene ontology biological process annotations and network construction of top pathways using clusterprofiler, where pathways related to fatty acid oxidation were observed in adipose (left) and chemotaxis/ECM remodeling in skeletal muscle (right). B-D, The same qvalue binning, top within-tissue and top peripheral enrichments were applied to intestinal GCG (B), liver FGF21 (C) and muscle IL6 (D). For these analyses all 310 individuals (across both sexes) were used and qvalue adjustments calculated using a Benjamini-Hochberg FDR adjustment.
Tissue-specific contributions to pan-organ gene-gene correlation structure.
A Heatmap showing all the number of gene-gene correlations across tissues which achieve significance relative to total number of genes in each pathway at biweigth midcorrelation student pvalue < 1e-3 (left column), pvalue < 1e-6 (left middle column) of BH-corrected qvalue <0.1 (right middle column) or BH-corrected qvalue<0.01 (right column). Within-tissue correlations are omitted from this analysis. B-D, Genes corresponding to each KEGG pathway shown were correlated both within and across all other organs where the number of genes which meet each students pvalue threshold are shown (y-axis). Tissues (x-axis) are rank-ordered by the number of genes which correlate for hsa04062 − Chemokine signaling pathway at pvalue<0.01 and shown for other KEGG terms, hsa04640 − Hematopoietic cell lineage (C) and hsa00190 − Oxidative phosphorylation (D) and additionally pvalue<1e-4 (right side).
Inter-individual transcript correlation structure and network architecture of liver PCSK9 and adipose PNPLA2.
A, distribution of pan-tissue genes correlated with liver PCSK9 expression (q<0.1), where 93% of genes were within liver (purple). B, Gene ontology (BP) overrepresentation test for the top 500 hepatic genes correlated with PCSK9 expression in liver. C, Undirected network constructed from liver genes (aqua) correlated with PCSK9, where those annotated for “cholesterol biosynthetic process” are colored in red. D-E, over-representation tests corresponding to the top-correlated genes with adipose (subcutaneous) PNPLA2 expression residing in adipose (D) or peripherally in skeletal muscle (E). F, Undirected network constructed from from the strongest correlated subcutaneous adipose tissue (light aqua) and muscle genes (dark blue) with PNPLA2 (black), where genes corresponding to GO terms annotated as “fatty acid beta oxidation” or “Muscle contraction” are colored purple or red, respectively. For these analyses all 310 individuals (across both sexes) were used and qvalue adjustments calculated using a Benjamini-Hochberg FDR adjustment. Network graphs generated based in Biweight midcorrelation coefficients, where edges are colored blue for positive correlations or red for negative correlations. Network edges represent positive (blue) and negative (red) correlations and the thicknesses are determined by coefficients. They are set for a range of bicor=0.6 (minimum to include) to bicor=0.99
HMDP tissue- and diet-specific correlations of sex hormone receptors.
The top 10 phenotypic traits which correlated to expression of androgen receptor (A), estrogen receptor 1 (B) or estrogen receptor 2 (C) colored by direction in the hybrid mouse diversity panel. Positive correlations are shown in light blue and negative correlations as sunset orange, where phenotypes (y-axis) are ordered by significance (x-axis, -log(pvalue) of correlation). Correlations are segregated by whether sex hormone receptors are expressed by gonadal adipose tissue (left two columns) in ∼100 HMDP strains fed a HFHS diet (left), normal chow diet (left middle) or liver-expressed receptors fed a HFHS diet (right middle) or normal chow diet (right).
