Hypermotifs in Biological Networks: TGFβ-Induced EMT as a Case Study

Complex systems describe a collection of entities and interactions influencing each other and are prevalent in various domains. Networks are one of the common ways to represent these complex systems across various disciplines. In biology, networks provide a mathematical constriction to interpret the association between biological molecules. Network motifs are the small subgraph patterns within the large biological networks which play several crucial functional roles. While network motifs like coherent feedforward loops are extensively analyzed, there are limited studies on how these network motifs are combined to form hypermotifs within the biological networks and the properties that may emerge from these hypermotifs are not extensively studied. Recent studies highlighted the prevailing role of hypermotifs in various contexts. This work presents some of the hypermotifs observed in regulating Epithelial Mesenchymal Transition (EMT) and cancer metastasis. Our study presents comprehensive system-level modeling and analysis of hypermotifs, highlighting their emergent behavior through discrete and continuous dynamic modeling approaches. The temporal regulation of the molecules involved in the hypermotif was demonstrated. These findings may enhance our understanding of network-based regulation in complex biological systems, including cancer metastasis.