MOLECULAR BIOCIRCUITS

2009 ◽  
Vol 23 (06) ◽  
pp. 773-789 ◽  
Author(s):  
OVIDIU LIPAN
Keyword(s):  
Systems Biology ◽  
Master Equation ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Stochastic Approach ◽  
Genetic Networks ◽  
Equation Approach ◽  
Master Equation Approach ◽  
Gene Regulatory

Systems biology aims to describe gene regulatory networks at both experimental and theoretical levels. Mathematical formalisms used at present to describe the behavior of genetic networks range from stochastic to deterministic. The stochastic approach is further subdivided and moves from Langevin to the Master equation. This review presents the Master equation approach.

scholarly journals Improving gene regulatory network structure using redundancy reduction in the MRNET algorithm

RSC Advances ◽  
2017 ◽  
Vol 7 (37) ◽  
pp. 23222-23233 ◽  
Author(s):  
Wei Liu ◽  
Wen Zhu ◽  
Bo Liao ◽  
Haowen Chen ◽  
Siqi Ren ◽  
...  
Keyword(s):  
Systems Biology ◽  
Gene Regulatory Network ◽  
Gene Regulatory Networks ◽  
Network Structure ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Central Problem ◽  
Expression Data ◽  
Redundancy Reduction ◽  
Gene Regulatory

Inferring gene regulatory networks from expression data is a central problem in systems biology.

scholarly journals Revisiting the reduction of stochastic models of genetic feedback loops with fast promoter switching

2019 ◽  
Author(s):  
J. Holehouse ◽  
R. Grima
Keyword(s):  
Transcriptional Regulation ◽  
Master Equation ◽  
Gene Regulatory Networks ◽  
Stochastic Models ◽  
Regulatory Networks ◽  
Burst Size ◽  
Protein Translation ◽  
Feedback Loops ◽  
Deterministic Models ◽  
Gene Regulatory

AbstractPropensity functions of the Hill-type are commonly used to model transcriptional regulation in stochastic models of gene expression. This leads to an effective reduced master equation for the mRNA and protein dynamics only. Based on deterministic considerations, it is often stated or tacitly assumed that such models are valid in the limit of rapid promoter switching. Here, starting from the chemical master equation describing promoter-protein interactions, mRNA transcription, protein translation and decay, we prove that in the limit of fast promoter switching, the distribution of protein numbers is different than that given by standard stochastic models with Hill-type propensities. We show the differences are pronounced whenever the protein-DNA binding rate is much larger than the unbinding rate, a special case of fast promoter switching. Furthermore we show using both theory and simulations that use of the standard stochastic models leads to drastically incorrect predictions for the switching properties of positive feedback loops and that these differences decrease with increasing mean protein burst size. Our results confirm that commonly used stochastic models of gene regulatory networks are only accurate in a subset of the parameter space consistent with rapid promoter switching.Statement of SignificanceA large number of models of gene regulatory networks in the literature assume that since promoter switching is fast then transcriptional regulation can be effectively modeled using Hill functions. While this approach can be rigorously justified for deterministic models, it is presently unclear if it is also the case for stochastic models. In this article we prove that this is not the case, i.e. stochastic models of gene regulatory systems, namely those with feedback loops, describing transcriptional regulation using Hill functions are only valid in a subset of parameter conditions consistent with fast promoter switching. We identify parameter regimes where these models are correct and where their predictions cannot be trusted.

scholarly journals Chip-seq and gene expression data for the identification of functional sub-pathways: a proof of concept in lung cancer

2020 ◽  
Author(s):  
Xanthoula Atsalaki ◽  
Lefteris Koumakis ◽  
George Potamias ◽  
Manolis Tsiknakis
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Systems Biology ◽  
Gene Expression Data ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Integrative Approach ◽  
Expression Data ◽  
Gene Regulatory

AbstractHigh-throughput technologies, such as chromatin immunoprecipitation (ChIP) with massively parallel sequencing (ChIP-seq) have enabled cost and time efficient generation of immense amount of genome data. The advent of advanced sequencing techniques allowed biologists and bioinformaticians to investigate biological aspects of cell function and understand or reveal unexplored disease etiologies. Systems biology attempts to formulate the molecular mechanisms in mathematical models and one of the most important areas is the gene regulatory networks (GRNs), a collection of DNA segments that somehow interact with each other. GRNs incorporate valuable information about molecular targets that can be corellated to specific phenotype.In our study we highlight the need to develop new explorative tools and approaches for the integration of different types of -omics data such as ChIP-seq and GRNs using pathway analysis methodologies. We present an integrative approach for ChIP-seq and gene expression data on GRNs. Using public microarray expression samples for lung cancer and healthy subjects along with the KEGG human gene regulatory networks, we identified ways to disrupt functional sub-pathways on lung cancer with the aid of CTCF ChIP-seq data, as a proof of concept.We expect that such a systems biology pipeline could assist researchers to identify corellations and causality of transcription factors over functional or disrupted biological sub-pathways.

scholarly journals Causal Concepts Guiding Model Specification in Systems Biology

Disputatio ◽  
2017 ◽  
Vol 9 (47) ◽  
pp. 499-527
Author(s):  
Dana Matthiessen
Keyword(s):  
Systems Biology ◽  
High Throughput ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Causal Structure ◽  
Model Specification ◽  
Biology I ◽  
Adequate Representation ◽  
Gene Regulatory ◽  
High Throughput Experiments

Abstract In this paper I analyze the process by which modelers in systems biology arrive at an adequate representation of the biological structures thought to underlie data gathered from high-throughput experiments. Contrary to views that causal claims and explanations are rare in systems biology, I argue that in many studies of gene regulatory networks modelers aim at a representation of causal structure. In addressing modeling challenges, they draw on assumptions informed by theory and pragmatic considerations in a manner that is guided by an interventionist conception of causal structure. While doubts have been raised about the applicability of this notion of causality to complex biological systems, it is here seen to be an adequate guide to inquiry.

COMPLEX NETWORKS EVOLUTIONARY DYNAMICS USING GENETIC ALGORITHMS

2012 ◽  
Vol 22 (07) ◽  
pp. 1250156 ◽  
Author(s):  
DANIEL AGUILAR-HIDALGO ◽  
ANTONIO CÓRDOBA ZURITA ◽  
Ma CARMEN LEMOS FERNÁNDEZ
Keyword(s):  
Genetic Algorithm ◽  
Systems Biology ◽  
Complex Networks ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Evolutionary Dynamics ◽  
Network Dynamics ◽  
Activity Level ◽  
Transformation Rules ◽  
Gene Regulatory

Gene regulatory networks set a second order approximation to genetics understanding, where the first order is the knowledge at the single gene activity level. With the increasing number of sequenced genomes, including humans, the time has come to investigate the interactions among myriads of genes that result in complex behaviors. These characteristics are included in the novel discipline of Systems Biology. The composition and unfolding of interactions among genes determine the activity of cells and, when is considered during development, the organogenesis. Hence the interest of building representative networks of gene expression and their time evolution, i.e. the structure as the network dynamics, for certain development processes. The complexity of this kind of problems makes imperative to analyze the problem in the field of network theory and the evolutionary dynamics of complex systems.All this has led us to investigate, in a first step, the evolutionary dynamics in generic networks. Thus, the results can be used in experimental researches in the field of Systems Biology. This research aims to decode the transformation rules governing the evolutionary dynamics in a network. To do this, a genetic algorithm has been implemented in which, starting from initial and ending network states, it is possible to determine the transformation dynamics between these states by using simple acting rules. The network description is the following: (a) The network node values in the initial and ending states can be active or inactive; (b) The network links can act as activators or repressors; (c) A set of rules is established in order to transform the initial state into the ending one; (d) Due to the low connectivity, frequently observed, in gene regulatory networks, each node will hold a maximum of three inputs with no restriction on outputs. The "chromosomes" of the genetic algorithm include two parts, one related to the node links and another related to the transformation rules.The implemented rules are based on certain genetic interactions behavior. The rules and their combinations are compound by logic conditions and set the bases to the network motifs formation, which are the building blocks of the network dynamics.The implemented algorithm is able to find appropriate dynamics in complex networks evolution among different states for several cases.

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