RT Journal Article
SR Electronic
T1 The combination of the functionalities of feedback circuits is determinant for the number and size of attractors of molecular networks
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 060608
DO 10.1101/060608
A1 Eugenio Azpeitia
A1 Stalin Muñoz
A1 Daniel González-Tokman
A1 Mariana Esther Martínez-Sánchez
A1 Nathan Weinstein
A1 Aurélien Naldi
A1 Elena R. Álvarez-Buylla
A1 David A Rosenblueth
A1 Luis Mendoza
YR 2016
UL http://biorxiv.org/content/early/2016/06/24/060608.abstract
AB 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 (motifs). Here, we analyze the behavior of pathways containing non-hierarchical and non-unidirectional 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 precise number and size of the attractors. We show that the different sets of 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 structures producing the epistasis results have remarkably similar sets of combinations of functionalities, that combined with other network properties could greatly improve epistasis analysis.