scholarly journals Degeneracy measures in biologically plausible random Boolean networks

2021 ◽  
Author(s):  
Basak Kocaoglu ◽  
William Alexander
Keyword(s):  
Gene Regulatory Networks ◽  
Biological Networks ◽  
Regulatory Networks ◽  
Biological Systems ◽  
Boolean Networks ◽  
Data Sets ◽  
Random Boolean Networks ◽  
Weighted Networks ◽  
Underlying Network ◽  
Gene Regulatory

Degeneracy, the ability of structurally different elements to perform similar functions, is a property of many biological systems. Systems exhibiting a high degree of degeneracy continue to exhibit the same macroscopic behavior following a lesion even though the underlying network dynamics are significantly different. Degeneracy thus suggests how biological systems can thrive despite changes to internal and external demands. Although degeneracy is a feature of network topologies and seems to be implicated in a wide variety of biological processes, research on degeneracy in biological networks is mostly limited to weighted networks (e.g., neural networks). To date, there has been no extensive investigation of information theoretic measures of degeneracy in other types of biological networks. In this paper, we apply existing approaches for quantifying degeneracy to random Boolean networks used for modeling biological gene regulatory networks. Using random Boolean networks with randomly generated rulesets to generate synthetic gene expression data sets, we systematically investigate the effect of network lesions on measures of degeneracy. Our results are comparable to measures of degeneracy using weighted networks, and this suggests that degeneracy measures may be a useful tool for investigating gene regulatory networks.

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 BioNetLink - An Architecture for Working with Network Data

2014 ◽  
Vol 11 (2) ◽  
pp. 68-79
Author(s):  
Matthias Klapperstück ◽  
Falk Schreiber
Keyword(s):  
Experimental Data ◽  
Biological Networks ◽  
Regulatory Networks ◽  
Large Data ◽  
Biological Data ◽  
Network Data ◽  
Data Sets ◽  
Dynamic Views ◽  
Gene Regulatory ◽  
Multiple Network

Summary The visualization of biological data gained increasing importance in the last years. There is a large number of methods and software tools available that visualize biological data including the combination of measured experimental data and biological networks. With growing size of networks their handling and exploration becomes a challenging task for the user. In addition, scientists also have an interest in not just investigating a single kind of network, but on the combination of different types of networks, such as metabolic, gene regulatory and protein interaction networks. Therefore, fast access, abstract and dynamic views, and intuitive exploratory methods should be provided to search and extract information from the networks. This paper will introduce a conceptual framework for handling and combining multiple network sources that enables abstract viewing and exploration of large data sets including additional experimental data. It will introduce a three-tier structure that links network data to multiple network views, discuss a proof of concept implementation, and shows a specific visualization method for combining metabolic and gene regulatory networks in an example.

scholarly journals Robustness and lethality in multilayer biological molecular networks

2019 ◽  
Author(s):  
Xueming Liu ◽  
Enrico Maiorino ◽  
Arda Halu ◽  
Joseph Loscalzo ◽  
Jianxi Gao ◽  
...  
Keyword(s):  
Biological Networks ◽  
Regulatory Networks ◽  
Metabolic Diseases ◽  
Biological Systems ◽  
Interaction Network ◽  
Network Models ◽  
Global Network ◽  
Molecular Networks ◽  
Cancer Genes ◽  
Gene Regulatory

AbstractRobustness is a prominent feature of most biological systems. In a cell, the structure of the interactions between genes, proteins, and metabolites has a crucial role in maintaining the cell’s functionality and viability in presence of external perturbations and noise. Despite advances in characterizing the robustness of biological systems, most of the current efforts have been focused on studying homogeneous molecular networks in isolation, such as protein-protein or gene regulatory networks, neglecting the interactions among different molecular substrates. Here we propose a comprehensive framework for understanding how the interactions between genes, proteins and metabolites contribute to the determinants of robustness in a heterogeneous biological network. We integrate heterogeneous sources of data to construct a multilayer interaction network composed of a gene regulatory layer, and protein-protein interaction layer and a metabolic layer. We design a simulated perturbation process to characterize the contribution of each gene to the overall system’s robustness, defined as its influence over the global network. We find that highly influential genes are enriched in essential and cancer genes, confirming the central role of these genes in critical cellular processes. Further, we determine that the metabolic layer is more vulnerable to perturbations involving genes associated to metabolic diseases. By comparing the robustness of the network to multiple randomized network models, we find that the real network is comparably or more robust than expected in the random realizations. Finally, we analytically derive the expected robustness of multilayer biological networks starting from the degree distributions within or between layers. These results provide new insights into the non-trivial dynamics occurring in the cell after a genetic perturbation is applied, confirming the importance of including the coupling between different layers of interaction in models of complex biological systems.

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’.

Improved Fuzzy Cognitive Maps for Gene Regulatory Networks Inference Based on Time Series Data

2021 ◽  
Author(s):  
Marzieh Emadi ◽  
Farsad Zamani Boroujeni ◽  
jamshid Pirgazi
Keyword(s):  
Time Series ◽  
Compressed Sensing ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Time Series Data ◽  
Cognitive Maps ◽  
Boolean Networks ◽  
Fuzzy Cognitive Maps ◽  
Series Data ◽  
Gene Regulatory

Abstract Recently with the advancement of high-throughput sequencing, gene regulatory network inference has turned into an interesting subject in bioinformatics and system biology. But there are many challenges in the field such as noisy data, uncertainty, time-series data with numerous gene numbers and low data, time complexity and so on. In recent years, many research works have been conducted to tackle these challenges, resulting in different methods in gene regulatory networks inference. A number of models have been used in modeling of the gene regulatory networks including Boolean networks, Bayesian networks, Markov model, relational networks, state space model, differential equations model, artificial neural networks and so on. In this paper, the fuzzy cognitive maps are used to model gene regulatory networks because of their dynamic nature and learning capabilities for handling non-linearity and inherent uncertainty. Fuzzy cognitive maps belong to the family of recurrent networks and are well-suited for gene regulatory networks. In this research study, the Kalman filtered compressed sensing is used to infer the fuzzy cognitive map for the gene regulatory networks. This approach, using the advantages of compressed sensing and Kalman filters, allows robustness to noise and learning of sparse gene regulatory networks from data with high gene number and low samples. In the proposed method, stream data and previous knowledge can be used in the inference process. Furthermore, compressed sensing finds likely edges and Kalman filter estimates their weights. The proposed approach uses a novel method to decrease the noise of data. The proposed method is compared to CSFCM, LASSOFCM, KFRegular, ABC, RCGA, ICLA, and CMI2NI. The results show that the proposed approach is superior to the other approaches in fuzzy cognitive maps learning. This behavior is related to the stability against noise and offers a proper balance between data error and network structure.

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.

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