Fig. 2. Our BA10 qPCR experiment replicated many diagnosis effects observed in the frontal cortex in meta-analyses of differential expression results from less sensitive transcriptional profiling methods (microarray, RNA-Seq).
In addition to detecting novel diagnosis effects in low-level expressed genes (HTR2B, DRD4), our BA10 qPCR experiment was able to detect diagnosis effects that were observed in the frontal cortex within our current meta-analysis of previous BA10 microarray studies and in a previously-published meta-analysis of RNA-Seq studies of adjacent frontal cortex. A To provide a more robust comparison, we re-annotated and re-analyzed two publicly available BA10 microarray datasets (Iwamoto et al. [20] and Maycox et al. [21]) and then performed a meta-analysis to identify the differential expression associated with SCHIZ. A scatterplot is shown illustrating the positive correlation (R = 0.243, P = 0.0175) between the differential expression (Log2FC) associated with SCHIZ in our BA10 microarray meta-analysis and the differential expression associated with SCHIZ in our BA10 qPCR experiment (Log2FC) for all genes that were present in both datasets (n = 95). The color of the data points signifies whether a gene showed a nominally significant effect of diagnosis in the microarray meta-analysis results (black: P < 0.05, brown: P > 0.05). B A scatterplot illustrating the positive correlation (R = 0.607, P = 6.604e-11) between the differential expression associated with SCHIZ (Log2FC) identified in a large (n = 384: 203 CTRL, 181 SCHIZ) meta-analysis of RNA-Seq data from the DLPFC and other frontal cortical (FC) tissue (Gandal et al. [34]) and the differential expression associated with SCHIZ in our BA10 qPCR experiment (Log2FC) for all genes that were present in both datasets (95 genes). The color of the data points signifies whether a gene showed a nominally significant effect of diagnosis in the DLPFC/FC Gandal RNA-Seq meta-analysis results (black: P < 0.05, brown: P > 0.05). C A scatterplot illustrating the positive correlation (R = 0.490, P = 4.61e-07) between the differential expression associated with BP (Log2FC) identified in a large (n = 171: 101 CTRL, 70 BP) meta-analysis of RNA-Seq data from the DLPFC and other frontal cortical tissue (Gandal et al. [34]) and the differential expression associated with BP in our BA10 qPCR experiment (Log2FC) for all genes that were present in both datasets (95 genes). The color of the data points signifies whether a gene showed a nominally significant effect of diagnosis in the DLPFC/FC Gandal RNA-Seq meta-analysis results (black: P < 0.05, brown: P > 0.05). Data points are labeled with official gene symbols for genes that show particularly large Log2FC in both datasets. Full statistical reporting for the correlations between the differential expression observed in different datasets can be found in Supplementary Table S9.