Fig. 1
From: Network-based identification of critical regulators as putative drivers of human cleft lip
Schematic flowchart for constructing and analyzing the comprehensive miRNA–TF co-regulatory networks in cleft lip (CL). (a) CL-related genes were collected and manually curated from main biomedical databases including Medline, PubMed and Embase. The miRNAs targeting these genes were identified from four miRNA-target interaction databases: miRanda, PITA, TargetScan and miRTarBase. (b) Four types of regulation relationships: TF-gene, TF-miRNA, miRNA-TF and miRNA-gene. (c) Three regulatory motifs measured by feed forward loop (FFL). (d) Construction of the miRNA–TF co-regulatory network. The combined network of all FFLs consisted of 8 miRNAs, 15 TFs, 26 genes and 163 edges. (e) Identification of critical genes (TFs, miRNAs and genes) and analysis of their potential functions. (f) Identification of network modules and analysis of their potential functions. (g) Extracting miRNA–TF co-regulatory subnetworks based on a specific pathway (Wnt pathway). (h) GO and pathway enrichment analysis. Blue ellipse: gene; orange rectangle: miRNA; green triangle: TF; blue line: miRNA-TF; orange line: miRNA-gene; green line: TF-miRNA; gray line: TF-gene