Fig. 2
From: Sex specific molecular networks and key drivers of Alzheimer’s disease
Sex-specific Co-expression Network Modules of AD Para-hippocampal Brain Region. A The top 15 MEGENA modules (with specific module number provided in the table) most associated with AD, which were most enriched for DEGs identified between AD and the control as well as significantly correlated with AD clinical traits with multiple tracks illustrating the different properties of the modules, such as strength of correlation between modules and the neuropathological/cognitive traits and significance of module enrichment for TCGs. The table showed the traits for the tracks #1–13 (the outmost track is the overall score). The tracks #2–5 corresponded to the correlations between a module and four traits including CDR, Plaque Density, CERAD, and Braak stage. Tracks #6–13 corresponded to the enrichment of DEG signatures (based on the comparisons including Medium vs High Braak stage, Low vs High Braak stage, MCI versus AD by CDR, Normal control versus AD by CDR, Definite AD versus Normal Control by CERAD, Definite AD versus Possible AD by CERAD, High versus Low Plaque density, Medium versus Low Plaque density) in modules. B Modules that were most enriched for neuron (left) and microglia (right) marker genes in the female AD network. The pie chart of each node indicates whether it was a DEG identified between AD and the control (upper half) or between women and men (lower half). Warm colors in the pie chart represented the upregulation of the gene in AD/women; cool colors in the pie chart represented the downregulation of the gene in AD/women. Nodes with large sizes and labels were sex-biased AD-associated candidate genes identified in this study. C Procedure for identification of KND genes for female and male AD. A summary score for each KND gene was calculated based on multiple p values derived from module-traits correlation and module-DEG enrichment analyses. LRP10 was identified as the top female KND candidate gene in the PHG from the MSBB cohort using the most stringent selection criteria (Criterion 1) with the highest rank score of 0.94 among all female KND candidate genes (the range of 0–1). D The top KND genes for female AD (left) and male AD (right). These candidates had high network connectivities (y-axis) and high summary scores (x-axis) (Supplemental Tables 10–11)