At the gene level, module genes showed extreme convergence of significant genes compared to the background genes in the network.
Further functional enrichment analysis of these module genes showed that at the pathway level, they were all consistently related to neuro- and immune-related pathways.
Elevated expression of mitotic checkpoint genes has been associated with chromosomal instability in breast cancer cells [ 40, 41], and the mitotic checkpoint module genes showed a considerable overlap with a signature for chromosome instability in tumors [ 42].
Conversely, ESR1-negative-module genes showed significantly higher methylation levels in cluster II than in cluster I (Mann–Whitney test: p < 0.001; see Fig 2C and D and Table SIX of Supporting Information).
As shown in box plots and barcode plots derived from Gene Set Enrichment Analysis, ESR1-positive-module genes showed higher methylation levels in cluster I than in cluster II (Mann–Whitney test: p < 0.001; see Fig 2C and D and Table SIX of Supporting Information).
To validate the module we hypothesized that the module genes would show significant gene expression changes in an independent material of allergen-challenged CD4+ cells from 19 patients with SAR.
Of note, results from one module suggest that microglial genes show increased expression in controls of Braak stage 2. To the best of our knowledge, this study represents the first transcriptional snapshot of CA3 in AD human brain, although multiple transcriptional studies of dementia have compared regions of differing degrees of vulnerability in order to gain insight into disease.
Within trait-correlated network modules, hub genes showing the highest interconnectivity to other genes in the module were selected as potential regulatory candidates for reverse transcription quantitative polymerase chain reaction (RT-qPCR) in thediversity set.
Preserved hub genes show highly significant evidence of being centrally located inside a preserved module.
The output at this final stage of Wigwams is a list of modules generated from genes showing statistically significant dependent co-expression, processed to optimize the number of different expression patterns contained in these modules and reduce redundancy between module gene membership.
