Fig. 1

Diagram of the network entropy and unbalanced motif approach to quantify cancer cellular network heterogeneity and modularity. a Workflow for gene co-expressed protein interaction network construction using large-scale RNA-Seq data from The Cancer Genome Atlas. Network entropy (b), and c balanced versus unbalanced motif analysis. d Quantifying cancer cellular network heterogeneity and modularity characterized by network entropy, and balanced versus unbalanced motifs in tumor versus matched normal samples, different stages of tumor progression, and anticancer drug sensitive versus resistant cancer cell lines. Based on the notion of Waddington’s landscape [17], network entropy and ratio of unbalanced versus balanced motifs were represented as the energy potential in Waddington’s landscape. High cellular network heterogeneity during tumorigenesis is characterized by elevated network entropy and high ratio of unbalanced versus balanced motifs