3.4 Critical lipid Co-expression network modules closely correlated with ICP
To clarify the relationships between lipids profile and the clinical characteristics of our study population, we next constructed Weighted Gene Co-expression Network Analysis (WGCNA) to identify clusters or modules that have similar expression patterns. In this analysis, we obtained 14 modules and the result showed that most lipids were clustered in turquoise, yellow and pink modules (Fig S2). Among the 14 modules, the pink module and purple module showed a significant positive correlation with TBA, ALT and AST levels, whereas the salmon module negatively correlated with TBA, ALT and AST levels (Fig 4A). A total of 30 lipids were included in these three modules, and we identified 11 differentially co-expressed lipids overlapped with the dysregulated lipids in both mild and severe ICP group (Fig S3A). Next, the CytoScape was used to screen hub lipids in pink, purple and salmon module based on the MCC algorithm. The top 4 lipids in the MCC algorithm were identified as hub lipids. As shown in Fig 4B, we identified PE (18:0p/20:1), dMePE (20:1p/16:0), PE (16:0p/22:1) and PE (38:2e) as hub lipids in the pink module. Among these four hub lipids, the expression level of PE (18:0p/20:1), dMePE (20:1p/16:0) and PE (16:0p/22:1) was significantly elevated in the mild and severe ICP group (Fig 4C). The network diagram also depicts the hub lipids in purple and salmon module (Fig S3B and Fig S3C).