scholarly journals Centrality Analysis Methods for Biological Networks and Their Application to Gene Regulatory Networks

2008 ◽  
Vol 2 ◽  
pp. GRSB.S702 ◽  
Author(s):  
Dirk Koschützki ◽  
Falk Schreiber
Keyword(s):  
Gene Regulatory Networks ◽  
Biological Networks ◽  
Regulatory Networks ◽  
Analysis Methods ◽  
Gene Regulatory ◽  
Centrality Analysis

scholarly journals Boolean factor graph model for biological systems: the yeast cell-cycle network

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Stephen Kotiang ◽  
Ali Eslami
Keyword(s):  
Cell Cycle ◽  
Yeast Cell ◽  
Gene Regulatory Networks ◽  
Biological Networks ◽  
Error Propagation ◽  
Regulatory Networks ◽  
Biological Systems ◽  
Yeast Cell Cycle ◽  
Computational Framework ◽  
Gene Regulatory

Abstract Background The desire to understand genomic functions and the behavior of complex gene regulatory networks has recently been a major research focus in systems biology. As a result, a plethora of computational and modeling tools have been proposed to identify and infer interactions among biological entities. Here, we consider the general question of the effect of perturbation on the global dynamical network behavior as well as error propagation in biological networks to incite research pertaining to intervention strategies. Results This paper introduces a computational framework that combines the formulation of Boolean networks and factor graphs to explore the global dynamical features of biological systems. A message-passing algorithm is proposed for this formalism to evolve network states as messages in the graph. In addition, the mathematical formulation allows us to describe the dynamics and behavior of error propagation in gene regulatory networks by conducting a density evolution (DE) analysis. The model is applied to assess the network state progression and the impact of gene deletion in the budding yeast cell cycle. Simulation results show that our model predictions match published experimental data. Also, our findings reveal that the sample yeast cell-cycle network is not only robust but also consistent with real high-throughput expression data. Finally, our DE analysis serves as a tool to find the optimal values of network parameters for resilience against perturbations, especially in the inference of genetic graphs. Conclusion Our computational framework provides a useful graphical model and analytical tools to study biological networks. It can be a powerful tool to predict the consequences of gene deletions before conducting wet bench experiments because it proves to be a quick route to predicting biologically relevant dynamic properties without tunable kinetic parameters.

scholarly journals Gene regulatory network stabilized by pervasive weak repressions: microRNA functions revealed by the May–Wigner theory

2019 ◽  
Vol 6 (6) ◽  
pp. 1176-1188 ◽  
Author(s):  
Yuxin Chen ◽  
Yang Shen ◽  
Pei Lin ◽  
Ding Tong ◽  
Yixin Zhao ◽  
...  
Keyword(s):  
Gene Regulatory Networks ◽  
Biological Networks ◽  
Regulatory Network ◽  
Mammalian Cells ◽  
Regulatory Networks ◽  
Yeast Cells ◽  
Gene Products ◽  
Mathematical Solution ◽  
Gene Regulatory ◽  
The Stability

Abstract Food web and gene regulatory networks (GRNs) are large biological networks, both of which can be analyzed using the May–Wigner theory. According to the theory, networks as large as mammalian GRNs would require dedicated gene products for stabilization. We propose that microRNAs (miRNAs) are those products. More than 30% of genes are repressed by miRNAs, but most repressions are too weak to have a phenotypic consequence. The theory shows that (i) weak repressions cumulatively enhance the stability of GRNs, and (ii) broad and weak repressions confer greater stability than a few strong ones. Hence, the diffuse actions of miRNAs in mammalian cells appear to function mainly in stabilizing GRNs. The postulated link between mRNA repression and GRN stability can be seen in a different light in yeast, which do not have miRNAs. Yeast cells rely on non-specific RNA nucleases to strongly degrade mRNAs for GRN stability. The strategy is suited to GRNs of small and rapidly dividing yeast cells, but not the larger mammalian cells. In conclusion, the May–Wigner theory, supplanting the analysis of small motifs, provides a mathematical solution to GRN stability, thus linking miRNAs explicitly to ‘developmental canalization’.

Network Analysis as a Grand Unifier in Biomedical Data Science

2018 ◽  
Vol 1 (1) ◽  
pp. 153-180 ◽  
Author(s):  
Patrick McGillivray ◽  
Declan Clarke ◽  
William Meyerson ◽  
Jing Zhang ◽  
Donghoon Lee ◽  
...  
Keyword(s):  
Gene Regulatory Networks ◽  
Biological Networks ◽  
Regulatory Networks ◽  
Data Science ◽  
Molecular Networks ◽  
Biomedical Data ◽  
Molecular Context ◽  
Gene Regulatory ◽  
Global Statistics ◽  
Key Aspects

Biomedical data scientists study many types of networks, ranging from those formed by neurons to those created by molecular interactions. People often criticize these networks as uninterpretable diagrams termed hairballs; however, here we show that molecular biological networks can be interpreted in several straightforward ways. First, we can break down a network into smaller components, focusing on individual pathways and modules. Second, we can compute global statistics describing the network as a whole. Third, we can compare networks. These comparisons can be within the same context (e.g., between two gene regulatory networks) or cross-disciplinary (e.g., between regulatory networks and governmental hierarchies). The latter comparisons can transfer a formalism, such as that for Markov chains, from one context to another or relate our intuitions in a familiar setting (e.g., social networks) to the relatively unfamiliar molecular context. Finally, key aspects of molecular networks are dynamics and evolution, i.e., how they evolve over time and how genetic variants affect them. By studying the relationships between variants in networks, we can begin to interpret many common diseases, such as cancer and heart disease.

scholarly journals Evolution in the Debian GNU/Linux software network: analogies and differences with gene regulatory networks

2020 ◽  
Vol 17 (163) ◽  
pp. 20190845
Author(s):  
Pablo Villegas ◽  
Miguel A. Muñoz ◽  
Juan A. Bonachela
Keyword(s):  
Information Processing ◽  
Gene Regulatory Networks ◽  
Biological Networks ◽  
Degree Distribution ◽  
Regulatory Networks ◽  
Average Distance ◽  
Scale Free ◽  
Software Network ◽  
Gene Regulatory ◽  
Over Time

Biological networks exhibit intricate architectures deemed to be crucial for their functionality. In particular, gene regulatory networks, which play a key role in information processing in the cell, display non-trivial architectural features such as scale-free degree distributions, high modularity and low average distance between connected genes. Such networks result from complex evolutionary and adaptive processes difficult to track down empirically. On the other hand, there exists detailed information on the developmental (or evolutionary) stages of open-software networks that result from self-organized growth across versions. Here, we study the evolution of the Debian GNU/Linux software network, focusing on the changes of key structural and statistical features over time. Our results show that evolution has led to a network structure in which the out-degree distribution is scale-free and the in-degree distribution is a stretched exponential. In addition, while modularity, directionality of information flow, and average distance between elements grew, vulnerability decreased over time. These features resemble closely those currently shown by gene regulatory networks, suggesting the existence of common adaptive pathways for the architectural design of information-processing networks. Differences in other hierarchical aspects point to system-specific solutions to similar evolutionary challenges.

scholarly journals Generating Ensembles of Gene Regulatory Networks to Assess Robustness of Disease Modules

2021 ◽  
Vol 11 ◽  
Author(s):  
James T. Lim ◽  
Chen Chen ◽  
Adam D. Grant ◽  
Megha Padi
Keyword(s):  
Gene Regulatory Networks ◽  
Biological Networks ◽  
Regulatory Networks ◽  
Network Inference ◽  
Disease Onset ◽  
Null Distribution ◽  
Generative Models ◽  
Consensus Clustering ◽  
Gene Regulatory ◽  
Disease Modules

The use of biological networks such as protein–protein interaction and transcriptional regulatory networks is becoming an integral part of genomics research. However, these networks are not static, and during phenotypic transitions like disease onset, they can acquire new “communities” (or highly interacting groups) of genes that carry out cellular processes. Disease communities can be detected by maximizing a modularity-based score, but since biological systems and network inference algorithms are inherently noisy, it remains a challenge to determine whether these changes represent real cellular responses or whether they appeared by random chance. Here, we introduce Constrained Random Alteration of Network Edges (CRANE), a method for randomizing networks with fixed node strengths. CRANE can be used to generate a null distribution of gene regulatory networks that can in turn be used to rank the most significant changes in candidate disease communities. Compared to other approaches, such as consensus clustering or commonly used generative models, CRANE emulates biologically realistic networks and recovers simulated disease modules with higher accuracy. When applied to breast and ovarian cancer networks, CRANE improves the identification of cancer-relevant GO terms while reducing the signal from non-specific housekeeping processes.

Dynamic Links and Evolutionary History in Simulated Gene Regulatory Networks

2010 ◽  
pp. 498-522
Author(s):  
T. Steiner ◽  
Y. Jin ◽  
L. Schramm ◽  
B. Sendhoff
Keyword(s):  
Gene Regulatory Networks ◽  
Biological Networks ◽  
Regulatory Networks ◽  
Evolutionary Process ◽  
Computational Method ◽  
Cellular Growth ◽  
Small Scale ◽  
Mutational Robustness ◽  
Gene Regulatory ◽  
Artificial Gene

In this chapter, we describe the use of evolutionary methods for the in silico generation of artificial gene regulatory networks (GRNs). These usually serve as models for biological networks and can be used for enhancing analysis methods in biology. We clarify our motivation in adopting this strategy by showing the importance of detailed knowledge of all processes, especially the regulatory dynamics of interactions undertaken during gene expression. To illustrate how such a methodology works, two different approaches to the evolution of small-scale GRNs with specified functions, are briefly reviewed and discussed. Thereafter, we present an approach to evolve medium sized GRNs with the ability to produce stable multi-cellular growth. The computational method employed allows for a detailed analysis of the dynamics of the GRNs as well as their evolution. We have observed the emergence of negative feedback during the evolutionary process, and we suggest its implication to the mutational robustness of the regulatory network which is further supported by evidence observed in additional experiments.

scholarly journals Identification, visualization, statistical analysis and mathematical modeling of high-feedback loops in gene regulatory networks

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Benjamin Nordick ◽  
Tian Hong
Keyword(s):  
Gene Regulatory Networks ◽  
Biological Networks ◽  
Regulatory Networks ◽  
Epithelial Mesenchymal Transition ◽  
Cell Lineage ◽  
Feedback Loops ◽  
Feedback Systems ◽  
Mesenchymal Transition ◽  
Dynamical Features ◽  
Gene Regulatory

Abstract Background Feedback loops in gene regulatory networks play pivotal roles in governing functional dynamics of cells. Systems approaches demonstrated characteristic dynamical features, including multistability and oscillation, of positive and negative feedback loops. Recent experiments and theories have implicated highly interconnected feedback loops (high-feedback loops) in additional nonintuitive functions, such as controlling cell differentiation rate and multistep cell lineage progression. However, it remains challenging to identify and visualize high-feedback loops in complex gene regulatory networks due to the myriad of ways in which the loops can be combined. Furthermore, it is unclear whether the high-feedback loop structures with these potential functions are widespread in biological systems. Finally, it remains challenging to understand diverse dynamical features, such as high-order multistability and oscillation, generated by individual networks containing high-feedback loops. To address these problems, we developed HiLoop, a toolkit that enables discovery, visualization, and analysis of several types of high-feedback loops in large biological networks. Results HiLoop not only extracts high-feedback structures and visualize them in intuitive ways, but also quantifies the enrichment of overrepresented structures. Through random parameterization of mathematical models derived from target networks, HiLoop presents characteristic features of the underlying systems, including complex multistability and oscillations, in a unifying framework. Using HiLoop, we were able to analyze realistic gene regulatory networks containing dozens to hundreds of genes, and to identify many small high-feedback systems. We found more than a 100 human transcription factors involved in high-feedback loops that were not studied previously. In addition, HiLoop enabled the discovery of an enrichment of high feedback in pathways related to epithelial-mesenchymal transition. Conclusions HiLoop makes the study of complex networks accessible without significant computational demands. It can serve as a hypothesis generator through identification and modeling of high-feedback subnetworks, or as a quantification method for motif enrichment analysis. As an example of discovery, we found that multistep cell lineage progression may be driven by either specific instances of high-feedback loops with sparse appearances, or generally enriched topologies in gene regulatory networks. We expect HiLoop’s usefulness to increase as experimental data of regulatory networks accumulate. Code is freely available for use or extension at https://github.com/BenNordick/HiLoop.

scholarly journals Fibration symmetries uncover the building blocks of biological networks

2020 ◽  
Vol 117 (15) ◽  
pp. 8306-8314 ◽  
Author(s):  
Flaviano Morone ◽  
Ian Leifer ◽  
Hernán A. Makse
Keyword(s):  
Gene Regulatory Networks ◽  
Biological Networks ◽  
Regulatory Networks ◽  
Biological Network ◽  
Building Blocks ◽  
Branching Ratios ◽  
Graph Representation ◽  
Systems Science ◽  
Gene Regulatory ◽  
Fibonacci Sequences

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.

Modeling Stochastic Gene Regulatory Networks Using Direct Solutions of Chemical Master Equation and Rare Event Sampling

2016 ◽  
pp. 80-122
Author(s):  
Youfang Cao ◽  
Anna Terebus ◽  
Jie Liang
Keyword(s):  
Master Equation ◽  
Gene Regulatory Networks ◽  
Biological Networks ◽  
Regulatory Networks ◽  
Rare Event ◽  
Planck Equation ◽  
Chemical Master Equation ◽  
Copy Numbers ◽  
Finite State ◽  
Gene Regulatory

Stochasticity plays important roles in many biological networks. A fundamental framework for studying the full stochasticity is the Discrete Chemical Master Equation (dCME). Under this framework, the combination of copy numbers of molecular species defines the microstate of the molecular interactions in the network. The probability distribution over these microstates provide a full description of the properties of a stochastic molecular network. However, it is challenging to solve a dCME. In this chapter, we will first discuss how to derive approximation methods including Fokker-Planck equation and the chemical Langevin equation from the dCME. We also discuss the widely used stochastic simulation method. After that, we focus on the direct solutions to the dCME. We first discuss the Finite State Projection (FSP) method, and then introduce the recently developed finite buffer method (fb-dCME) for directly solving both steady state and time-evolving probability landscape of dCME. We show the advantages of the fb-dCME method using two realistic gene regulatory networks.

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