Figure 1.
Overview of analysis pipeline.
Figure 2.
Expression variance is stable under different normalization strategies.
A. Assessing the impact of normalization strategies on genome-wide variance distribution for the hONS stem cells and fibroblasts from the control group. B. Venn diagram demonstrating the geneset overlap of low-variance (left) or high-variance (right) identified from representative normalization strategies. There was a >75% concordance in the low-variance groups and a >90% concordance in the high-variance groups.
Table 1.
The top 21 most discriminating KEGG pathways between the neuronal stem cells obtained from the disease and healthy control donor groups.
Figure 3.
Distribution of variance patterns in the top 5 attract pathways for hONS and fibroblast cells.
Chi-square goodness of fit was used to determine if variance profiles differed significantly from the expected 25∶50∶25% patterns.
Figure 4.
Expression variance discriminates between disease groups.
A. Box plots showing whole-genome phenotype-specific mean expression levels and the corresponding CVs for hONS cells derived from the Control, PD, and SZ patient groups. As can be seen, there is no difference in the average log2(expression) measures but noticeable differences in the CVs. Using a two-sample t-test, there is a significant difference between the SZ and Control groups (p-value<2.2×10−16) and the PD and Control groups (p-value<0.0013). B. The observation of increase in high-variance genes for PD and increase in low-variance genes for SZ persists with different percentile cutoffs applied to the variance distribution in the MAPK signaling pathway. C. Ratios of gene counts for the attract pathways, showing a trend towards high-variance genes for PD and a significant increase in low-variance genes for SZ.
Figure 5.
MAPK interaction networks and degree distribution density curves for the highly-constrained (red) and lowly-constrained (green) genes.
p-values assess the significance of how different the two degree distributions are. The “Mid Variability” genes, falling between the 25th and 75th percentile of CV values, are shown in gray for comparison.