Fig. 3: dGCNA outperforms DESeq2 for replication of T2D-affected genes between datasets and the effect of target genes on Ins1 and Ins2 mRNA, and on glucose-stimulated insulin secretion.

A Overlap of genes identified with dGCNA in dataset 1 and dataset 2. B Overlap of GO-terms for dGCNA genes for dataset 1 and dataset 2. C Comparison of overlap of genes between dataset 1 and dataset 2 using DESeq2 and dGCNA on top-ranked 50–800 genes. D siRNA knockdown of Tmem176a/b, Cebpg, Gabarap, Spire1, or Atraid resulted in increased Ins1 mRNA levels (data presented as log₁₀-fold change of scrambled siRNA control (NC)). E Knockdown of Dbi, Cebpg, Dstn, Gabarap, or Atraid resulted in increased Ins2 mRNA levels in INS-1 832/13 cells. F Knockdown of Cebpg, Gabarap, Spire1, or Atraid caused increased insulin secretion in INS-1 832/13 cells at 16.7 mM glucose. At 16.7 mM glucose with IBMX, knockdown of Tmem176a/b, Cebpg, Gabarap, Spire1, or Atraid resulted in increased insulin secretion. D–E n = 6 per condition. F n = 6 per condition except for Cebpg (n = 7) and Tmem176a/b (n = 5). Data in (D–F) is presented as box plots. Hinges of the box represent the 25th and 75th percentiles, and the line in the box is the median. Whiskers are min and max values. *p < 0.05, **p < 0.01, ***p < 0.001. Two-tailed Student’s t-test was used in (D) and (E). One-way ANOVA, followed by Tukey’s post hoc test, was used in (F). See also Supplementary Data 4 and Figs. S5–S7. Source data are provided as a Source Data file.