Dataset Information

The combination of the functionalities of feedback circuits is determinant for the attractors' number and size in pathway-like Boolean networks.

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.

SUBMITTER: Azpeitia E

PROVIDER: S-EPMC5301197 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The combination of the functionalities of feedback circuits is determinant for the attractors' number and size in pathway-like Boolean networks.

Azpeitia Eugenio E Muñoz Stalin S González-Tokman Daniel D Martínez-Sánchez Mariana Esther ME Weinstein Nathan N Naldi Aurélien A Álvarez-Buylla Elena R ER Rosenblueth David A DA Mendoza Luis L

Scientific reports 20170210

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 hierarc ...[more]

PMID: 28186191

Similar Datasets

Project description:BackgroundBoolean models are increasingly used to study biological signaling networks. In a Boolean network, nodes represent biological entities such as genes, proteins or protein complexes, and edges indicate activating or inhibiting influences of one node towards another. Depending on the input of activators or inhibitors, Boolean networks categorize nodes as either active or inactive. The formalism is appealing because for many biological relationships, we lack quantitative information about binding constants or kinetic parameters and can only rely on a qualitative description of the type "A activates (or inhibits) B". A central aim of Boolean network analysis is the determination of attractors (steady states and/or cycles). This problem is known to be computationally complex, its most important parameter being the number of network nodes. Various algorithms tackle it with considerable success. In this paper we present an algorithm, which extends the size of analyzable networks thanks to simple and intuitive arguments.ResultsWe present lnet, a software package which, in fully asynchronous updating mode and without any network reduction, detects the fixed states of Boolean networks with up to 150 nodes and a good part of any present cycles for networks with up to half the above number of nodes. The algorithm goes through a complete enumeration of the states of appropriately selected subspaces of the entire network state space. The size of these relevant subspaces is small compared to the full network state space, allowing the analysis of large networks. The subspaces scanned for the analyses of cycles are larger, reducing the size of accessible networks. Importantly, inherent in cycle detection is a classification scheme based on the number of non-frozen nodes of the cycle member states, with cycles characterized by fewer non-frozen nodes being easier to detect. It is further argued that these detectable cycles are also the biologically more important ones. Furthermore, lnet also provides standard Boolean analysis features such as node loop detection.Conclusionslnet is a software package that facilitates the analysis of large Boolean networks. Its intuitive approach helps to better understand the network in question.

Dataset Information

The combination of the functionalities of feedback circuits is determinant for the attractors' number and size in pathway-like Boolean networks.

Publications

The combination of the functionalities of feedback circuits is determinant for the attractors' number and size in pathway-like Boolean networks.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets