Fig. 5.

UPR activation positively correlates with steatosis incidence. (A) Heat map of UPR target gene expression in the liver, with genes in columns and individual clutches in rows. Blue and red indicates below and above average, respectively, for each column. Supervised clustering was performed according to Tm concentration (first) and steatosis incidence (second) and was unsupervised for gene order. Brackets reflect the results of unsupervised clustering of the genes. The colored bar on the left represents steatosis incidence (see legend: dark blue, 0%; white, 50%; dark red, 100%). The raw data are listed in supplementary material Table S2. (B) First principal component (PC1) of the UPR gene expression for each clutch was plotted according to Tm concentration, with the box indicating the 75th and 25th quartile of the data, the whiskers indicating the 90th and 10th percentile and the cross line indicating the median. (C) Scatter plot representing correlation between PC1 and steatosis incidence in larvae treated with different doses of Tm. Each dot represents a single clutch and is assigned a different color corresponding to UPR subclass (blue, white and red characterize homeostatic, intermediate and stressed UPR, respectively). A least squares linear model fit (blue line) with 95% prediction error bands (gray overlay) was superimposed. (D) Plot of PC1 for DMSO (control; blue), 1 μg/ml BFA (green), 0.75 μM Tg (orange) and 1 μg/ml Tm (red). (E) Scatter plot representing correlation between PC1 and steatosis incidence in larvae treated with DMSO (blue), 0.75 μM Tg (orange) and 0.25–1 μg/ml Tm (red) using the same model as in C. The correlation between PC1 and steatosis has P<0.001, determined by the Spearman test. (F) Kernel density estimate of the distribution of the UPR-PC1 signature in three sets of clinical samples. Per-group average is marked with a thick black vertical line. *P<0.1, **P<0.01, ***P<0.005, calculated using paired Wilcoxon test.