Figure 1. Systems Biology Analysis Flow Chart Depicting the Process of Identifying CHD Causal Modules and Key Drivers (KDs).
The overall analysis includes 3 steps. First, coexpression networks are constructed from CHD cases and controls separately. CHD differential modules (DMs) are then identified by comparing the network structures between cases and controls. Step 2, the DMs are then integrated with GWAS of CHD and related traits using a SNP Set Enrichment Analysis (SSEA) to identify causal DMs. Third, key regulatory genes or KDs are identified for the causal DMs based on directional networks derived from independent studies using a Key Driver Analysis (KDA) algorithm.