Author:
Azpeitia Eugenio,Muñoz Stalin,González-Tokman Daniel,Martínez-Sánchez Mariana Esther,Weinstein Nathan,Naldi Aurélien,Álvarez-Buylla Elena R.,Rosenblueth David A.,Mendoza Luis
Abstract
Abstract
Molecular regulation was initially assumed to follow both a unidirectional and a hierarchical organization forming pathways. Regulatory processes, however, form highly interlinked networks with non-hierarchical and non-unidirectional structures that contain statistically overrepresented circuits or motifs. Here, we analyze the behavior of pathways containing non-unidirectional (i.e. bidirectional) and non-hierarchical interactions that create motifs. In comparison with unidirectional and hierarchical pathways, our pathways have a high diversity of behaviors, characterized by the size and number of attractors. Motifs have been studied individually showing that feedback circuit motifs regulate the number and size of attractors. It is less clear what happens in molecular networks that usually contain multiple feedbacks. Here, we find that the way feedback circuits couple to each other (i.e., the combination of the functionalities of feedback circuits) regulate both the number and size of the attractors. We show that the different expected results of epistasis analysis (a method to infer regulatory interactions) are produced by many non-hierarchical and non-unidirectional structures. Thus, these structures cannot be correctly inferred by epistasis analysis. Finally, we show that the combinations of functionalities, combined with other network properties, allow for a better characterization of regulatory structures.
Publisher
Springer Science and Business Media LLC
Reference37 articles.
1. Huang, L. S. & Sternberg, P. W. Genetic dissection of developmental pathways. WormBook 14, 1–19 (2006).
2. Chen, H., Wang, G., Simha, R., Du, C. & Zeng, C. Boolean Models of Biological Processes Explain Cascade-Like Behavior. Scientific Reports 7, 20067 EP- (2016).
3. Zhang, Y., Ouyang, Q. & Geng, Z. Topological origin of global attractors in gene regulatory networks. Science China Physics, Mechanics & Astronomy 58, 1–8 (2014).
4. Barabasi, A.-L. & Oltvai, Z. N. Network biology: understanding the cell's functional organization. Nat Rev Genet 5, 101–113 (2004).
5. Milo, R. et al. Network Motifs: Simple Building Blocks of Complex Networks. Science 298, 824–827 (2002).
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