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Symmetry principles have proven important in physics, deep learning and geometry, allowing for the reduction of complicated systems to simpler, more comprehensible models that preserve the system's features of interest. Biological systems often show a high level of complexity and consist of a high number of interacting parts. Using symmetry fibrations, the relevant symmetries for biological 'message-passing' networks, we reduced the gene regulatory networks of E. coli and B. subtilis bacteria in a way that preserves information flow and highlights the computational capabilities of the network. Nodes that share isomorphic input trees are grouped into equivalence classes called fibers, whereby genes that receive signals with the same 'history' belong to one fiber and synchronize. We further reduce the networks to its computational core by removing "dangling ends" via k-core decomposition. The computational core of the network consists of a few strongly connected components in which signals can cycle while signals are transmitted between these "information vortices" in a linear feed-forward manner. These components are in charge of decision making in the bacterial cell by employing a series of genetic toggle-switch circuits that store memory, and oscillator circuits. These circuits act as the central computation machine of the network, whose output signals then spread to the rest of the network.
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The main motivation for this paper is to characterize network synchronizability for the case of cluster synchronization (CS), in an analogous fashion to Barahona and Pecora [Phys. Rev. Lett. 89, 054101 (2002)] for the case of complete synchronization. We find this problem to be substantially more complex than the original one. We distinguish between the two cases of networks with intertwined clusters and no intertwined clusters and between the two cases that the master stability function is negative either in a bounded range or in an unbounded range of its argument. Our proposed definition of cluster synchronizability is based on the synchronizability of each individual cluster within a network. We then attempt to generalize this definition to the entire network. For CS, the synchronous solution for each cluster may be stable, independent of the stability of the other clusters, which results in possibly different ranges in which each cluster synchronizes (isolated CS). For each pair of clusters, we distinguish between three different cases: Matryoshka cluster synchronization (when the range of the stability of the synchronous solution for one cluster is included in that of the other cluster), partially disjoint cluster synchronization (when the ranges of stability of the synchronous solutions partially overlap), and complete disjoint cluster synchronization (when the ranges of stability of the synchronous solutions do not overlap).
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Recent studies have revealed the interplay between the structure of network circuits with fibration symmetries and the functionality of biological networks within which they have been identified. The presence of these symmetries in complex networks predicts the phenomenon of cluster synchronization, which produces patterns of a synchronized group of nodes. Here, we present a fast, and memory efficient, algorithm to identify fibration symmetries in networks. The algorithm is particularly suitable for large networks since it has a runtime of complexity O(Mlogâ¡N) and requires O(M+N) of memory resources, where N and M are the number of nodes and edges in the network, respectively. The algorithm is a modification of the so-called refinement paradigm to identify circuits that are symmetrical to information flow (i.e., fibers) by finding the coarsest refinement partition over the network. Finally, we show that the algorithm provides an optimal procedure for identifying fibers, overcoming current approaches used in the literature.
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AlgoritmosRESUMO
Computation of correlated ionic transport properties from molecular dynamics in the Green-Kubo formalism is expensive, as one cannot rely on the affordable mean square displacement approach. We use spectral decomposition of the short-time ionic displacement covariance to learn a set of diffusion eigenmodes that encode the correlation structure and form a basis for analyzing the ionic trajectories. This allows systematic reduction of the uncertainty and accelerate computations of ionic conductivity in systems with a steady-state correlation structure. We provide mathematical and numerical proofs of the method's robustness and demonstrate it on realistic electrolyte materials.
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BACKGROUND: Gene regulatory networks coordinate the expression of genes across physiological states and ensure a synchronized expression of genes in cellular subsystems, critical for the coherent functioning of cells. Here we address the question whether it is possible to predict gene synchronization from network structure alone. We have recently shown that synchronized gene expression can be predicted from symmetries in the gene regulatory networks described by the concept of symmetry fibrations. We showed that symmetry fibrations partition the genes into groups called fibers based on the symmetries of their 'input trees', the set of paths in the network through which signals can reach a gene. In idealized dynamic gene expression models, all genes in a fiber are perfectly synchronized, while less idealized models-with gene input functions differencing between genes-predict symmetry breaking and desynchronization. RESULTS: To study the functional role of gene fibers and to test whether some of the fiber-induced coexpression remains in reality, we analyze gene fibrations for the gene regulatory networks of E. coli and B. subtilis and confront them with expression data. We find approximate gene coexpression patterns consistent with symmetry fibrations with idealized gene expression dynamics. This shows that network structure alone provides useful information about gene synchronization, and suggest that gene input functions within fibers may be further streamlined by evolutionary pressures to realize a coexpression of genes. CONCLUSIONS: Thus, gene fibrations provide a sound conceptual tool to describe tunable coexpression induced by network topology and shaped by mechanistic details of gene expression.
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Escherichia coli , Redes Reguladoras de Genes , Escherichia coli/genética , Expressão Gênica , FenótipoRESUMO
We show that logic computational circuits in gene regulatory networks arise from a fibration symmetry breaking in the network structure. From this idea we implement a constructive procedure that reveals a hierarchy of genetic circuits, ubiquitous across species, that are surprising analogues to the emblematic circuits of solid-state electronics: starting from the transistor and progressing to ring oscillators, current-mirror circuits to toggle switches and flip-flops. These canonical variants serve fundamental operations of synchronization and clocks (in their symmetric states) and memory storage (in their broken symmetry states). These conclusions introduce a theoretically principled strategy to search for computational building blocks in biological networks, and present a systematic route to design synthetic biological circuits.
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Biologia Computacional/métodos , Redes Reguladoras de Genes , Biologia Sintética/métodos , Algoritmos , Animais , Arabidopsis , Bacillus subtilis , Simulação por Computador , Eletrônica , Escherichia coli , Humanos , Modelos Teóricos , Mycobacterium tuberculosis , Oscilometria , SalmonellaRESUMO
A major ambition of systems science is to uncover the building blocks of any biological network to decipher how cellular function emerges from their interactions. Here, we introduce a graph representation of the information flow in these networks as a set of input trees, one for each node, which contains all pathways along which information can be transmitted in the network. In this representation, we find remarkable symmetries in the input trees that deconstruct the network into functional building blocks called fibers. Nodes in a fiber have isomorphic input trees and thus process equivalent dynamics and synchronize their activity. Each fiber can then be collapsed into a single representative base node through an information-preserving transformation called "symmetry fibration," introduced by Grothendieck in the context of algebraic geometry. We exemplify the symmetry fibrations in gene regulatory networks and then show that they universally apply across species and domains from biology to social and infrastructure networks. The building blocks are classified into topological classes of input trees characterized by integer branching ratios and fractal golden ratios of Fibonacci sequences representing cycles of information. Thus, symmetry fibrations describe how complex networks are built from the bottom up to process information through the synchronization of their constitutive building blocks.