title: Analysis of diverse regulatory networks in a hierarchical context shows consistent tendencies for collaboration in the middle levels.
abstract: Gene regulatory networks have been shown to share some common aspects with commonplace social governance structures. Thus, we can get some intuition into their organization by arranging them into well-known hierarchical layouts. These hierarchies, in turn, can be placed between the extremes of autocracies, with well-defined levels and clear chains of command, and democracies, without such defined levels and with more co-regulatory partnerships between regulators. In general, the presence of partnerships decreases the variation in information flow amongst nodes within a level, more evenly distributing stress. Here we study various regulatory networks (transcriptional, modification, and phosphorylation) for five diverse species, Escherichia coli to human. We specify three levels of regulators--top, middle, and bottom--which collectively govern the non-regulator targets lying in the lowest fourth level. We define quantities for nodes, levels, and entire networks that measure their degree of collaboration and autocratic vs. democratic character. We show individual regulators have a range of partnership tendencies: Some regulate their targets in combination with other regulators in local instantiations of democratic structure, whereas others regulate mostly in isolation, in more autocratic fashion. Overall, we show that in all networks studied the middle level has the highest collaborative propensity and coregulatory partnerships occur most frequently amongst midlevel regulators, an observation that has parallels in corporate settings where middle managers must interact most to ensure organizational effectiveness. There is, however, one notable difference between networks in different species: The amount of collaborative regulation and democratic character increases markedly with overall genomic complexity.
authors.affiliation: Program in Computational Biology and Bioinformatics, Yale University, Bass 426, 266 Whitney Avenue, New Haven, CT 06520, USA.
authors.forename: Nitin
authors.initials: N
authors.lastname: Bhardwaj
authors.forename: Koon-Kiu
authors.initials: KK
authors.lastname: Yan
authors.forename: Mark B
authors.initials: MB
authors.lastname: Gerstein
mesh_terms: D000818:Animals; D004926:Escherichia coli / Q000235:genetics; D005786:Gene Expression Regulation; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D016678:Genome; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D015233:Models, Statistical; D009169:Mycobacterium tuberculosis / Q000235:genetics; D010766:Phosphorylation; D051381:Rats; D013045:Species Specificity