Fig. 1: TMT AD protein co-expression network. | Nature Neuroscience

Fig. 1: TMT AD protein co-expression network.

From: Large-scale deep multi-layer analysis of Alzheimer’s disease brain reveals strong proteomic disease-related changes not observed at the RNA level

Fig. 1: TMT AD protein co-expression network.The alt text for this image may have been generated using AI.

a–c, 516 DLPFC tissues from the ROSMAP (n = 84 control, 148 AsymAD and 108 AD) and the Banner Sun Health Brain Bank (Banner, n = 26 control, 58 AsymAD and 92 AD) were analyzed by TMT-MS-based proteomics (a). After outlier removal and data processing, a total of 8,619 proteins were quantified across 488 cases, which were analyzed by both differential expression and co-expression approaches. b, A protein co-expression network was built using WGCNA, which consisted of 44 protein co-expression modules. Module relatedness is shown in the central dendrogram. GO analysis was used to identify the principal biology represented by each module. Modules that did not have a clear ontology were not assigned an ontology term. Module eigenproteins were correlated with neuropathological and cognitive traits present in the ROSMAP and Banner cohorts (red, positive correlation; blue, negative correlation). The global pathology, Lewy body stage, TDP-43 stage and global cognitive level traits were present only in ROSMAP. Twelve of the 44 modules that were most highly correlated to neuropathological and/or cognitive traits are in bold, with the four most strongly trait-related modules highlighted in red. The cell type nature of each module was assessed by module protein overlap with cell-type-specific marker lists of neurons, oligodendrocytes, astrocytes, microglia and endothelia. c, Module eigenprotein levels by case status for the 12 most strongly trait-correlated modules bolded in b. Modules are grouped by those that change in AsymAD (n = 4, left) and those that change only in AD (n = 8, right). n = 106 control, 200 AsymAD and 182 AD. Differences in module eigenprotein by case status were assessed by one-way ANOVA with Tukey test. *P < 0.05 and ***P < 0.001. Box plots represent the median and 25th and 75th percentiles, and box hinges represent the interquartile range of the two middle quartiles within a group. Data points up to 1.5 times the interquartile range from the box hinge define the extent of whiskers (error bars). Cntl, control; MHC, major histocompatibility complex.

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