Compartment-specific protein interactions in beryllium lung disease

Abstract

The study provides insights into proteins that may be relevant in BeS and CBD. It provides a framework to investigate the global changes in lung compartment-specific inflammatory cells to better understand the potential interplay of proteins in CBD. https://bit.ly/3PLNTXC.

FIGURE 1

Protein pathways and modules linked to beryllium sensitisation (BeS) and chronic beryllium disease (CBD). Quantile normalised and log transformed protein abundances were analysed for identifying differentially abundant proteins (DAPs) in the three comparison groups as well as protein modules that were different in the three groups using Weighted Gene Co-expression Network Analysis in R. a) Overview of the proteins with differential abundance (DA) (p<0.05). b) Heatmap of proteins that demonstrated a significant monotonic increase or decrease in their abundance going from controls to BeS to CBD. c) “Overlapping analysis” in Ingenuity Pathway Analysis (IPA) for canonical pathways mapping to DAPs in BeS and CBD comparison. The edges (i.e., the lines drawn between two related pathways/nodes) represent the relationship of these pathways and are shown only between any pair of pathways that have at least four shared proteins. Moreover, the thickness of the edges is proportional to the total number of shared proteins in the connected pathways with thicker lines indicative of a larger number. Highly connected pathways such sirtuin and oestrogen receptor signalling may be critical in BeS and CBD pathogenesis. d) The results of Weighted Gene Co-expression Network Analysis (WGCNA) where 14 distinct modules were identified. Several modules identified by WGCNA demonstrate DA in BeS or CBD compared to controls and BeS compared with CBD. False discovery rate (FDR) adjusted p-values for each pairwise comparison of module eigen-protein loadings as obtained using t-tests on regression coefficients from linear mixed models. Those with an FDR <0.05 are highlighted in red.