scholarly journals Modelling Three Dimensional Gene Regulatory Networks

2021 ◽  
Vol 16 ◽  
pp. 755-763
Author(s):  
Inna Samuilik ◽  
Felix Sadyrbaev

We consider the three-dimensional gene regulatory network (GRN in short). This model consists of ordinary differential equations of a special kind, where the nonlinearity is represented by a sigmoidal function and the linear part is present also. The evolution of GRN is described by the solution vector X(t), depending on time. We describe the changes that system undergoes if the entries of the regulatory matrix are perturbed in some way.

RSC Advances ◽  
2017 ◽  
Vol 7 (37) ◽  
pp. 23222-23233 ◽  
Author(s):  
Wei Liu ◽  
Wen Zhu ◽  
Bo Liao ◽  
Haowen Chen ◽  
Siqi Ren ◽  
...  

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


2020 ◽  
Vol 36 (19) ◽  
pp. 4885-4893 ◽  
Author(s):  
Baoshan Ma ◽  
Mingkun Fang ◽  
Xiangtian Jiao

Abstract Motivation Gene regulatory networks (GRNs) capture the regulatory interactions between genes, resulting from the fundamental biological process of transcription and translation. In some cases, the topology of GRNs is not known, and has to be inferred from gene expression data. Most of the existing GRNs reconstruction algorithms are either applied to time-series data or steady-state data. Although time-series data include more information about the system dynamics, steady-state data imply stability of the underlying regulatory networks. Results In this article, we propose a method for inferring GRNs from time-series and steady-state data jointly. We make use of a non-linear ordinary differential equations framework to model dynamic gene regulation and an importance measurement strategy to infer all putative regulatory links efficiently. The proposed method is evaluated extensively on the artificial DREAM4 dataset and two real gene expression datasets of yeast and Escherichia coli. Based on public benchmark datasets, the proposed method outperforms other popular inference algorithms in terms of overall score. By comparing the performance on the datasets with different scales, the results show that our method still keeps good robustness and accuracy at a low computational complexity. Availability and implementation The proposed method is written in the Python language, and is available at: https://github.com/lab319/GRNs_nonlinear_ODEs Supplementary information Supplementary data are available at Bioinformatics online.


2021 ◽  
Author(s):  
Deborah Weighill ◽  
Marouen Ben Guebila ◽  
Kimberly Glass ◽  
John Quackenbush ◽  
John Platig

AbstractThe majority of disease-associated genetic variants are thought to have regulatory effects, including the disruption of transcription factor (TF) binding and the alteration of downstream gene expression. Identifying how a person’s genotype affects their individual gene regulatory network has the potential to provide important insights into disease etiology and to enable improved genotype-specific disease risk assessments and treatments. However, the impact of genetic variants is generally not considered when constructing gene regulatory networks. To address this unmet need, we developed EGRET (Estimating the Genetic Regulatory Effect on TFs), which infers a genotype-specific gene regulatory network (GRN) for each individual in a study population by using message passing to integrate genotype-informed TF motif predictions - derived from individual genotype data, the predicted effects of variants on TF binding and gene expression, and TF motif predictions - with TF protein-protein interactions and gene expression. Comparing EGRET networks for two blood-derived cell lines identified genotype-associated cell-line specific regulatory differences which were subsequently validated using allele-specific expression, chromatin accessibility QTLs, and differential TF binding from ChIP-seq. In addition, EGRET GRNs for three cell types across 119 individuals captured regulatory differences associated with disease in a cell-type-specific manner. Our analyses demonstrate that EGRET networks can capture the impact of genetic variants on complex phenotypes, supporting a novel fine-scale stratification of individuals based on their genetic background. EGRET is available through the Network Zoo R package (netZooR v0.9; netzoo.github.io).


2019 ◽  
Vol 1 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Felikss Sadirbajevs

The system of two the first order ordinary differential equations arising in the gene regulatory networks theory is studied. The structure of attractors for this system is described for three important behavioral cases: activation, inhibition, mixed activation-inhibition. The geometrical approach combined with the vector field analysis allows treating the problem in full generality. A number of propositions are stated and the proof is geometrical, avoiding complex analytic. Although not all the possible cases are considered, the instructions are given what to do in any particular situation.


2019 ◽  
Author(s):  
Zhang Zhang ◽  
Lifei Wang ◽  
Shuo Wang ◽  
Ruyi Tao ◽  
Jingshu Xiao ◽  
...  

SummaryReconstructing gene regulatory networks (GRNs) and inferring the gene dynamics are important to understand the behavior and the fate of the normal and abnormal cells. Gene regulatory networks could be reconstructed by experimental methods or from gene expression data. Recent advances in Single Cell RNA sequencing technology and the computational method to reconstruct trajectory have generated huge scRNA-seq data tagged with additional time labels. Here, we present a deep learning model “Neural Gene Network Constructor” (NGNC), for inferring gene regulatory network and reconstructing the gene dynamics simultaneously from time series gene expression data. NGNC is a model-free heterogenous model, which can reconstruct any network structure and non-linear dynamics. It consists of two parts: a network generator which incorporating gumbel softmax technique to generate candidate network structure, and a dynamics learner which adopting multiple feedforward neural networks to predict the dynamics. We compare our model with other well-known frameworks on the data set generated by GeneNetWeaver, and achieve the state of the arts results both on network reconstruction and dynamics learning.


2019 ◽  
Vol 6 (6) ◽  
pp. 1176-1188 ◽  
Author(s):  
Yuxin Chen ◽  
Yang Shen ◽  
Pei Lin ◽  
Ding Tong ◽  
Yixin Zhao ◽  
...  

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’.


2008 ◽  
Vol 19 (02) ◽  
pp. 283-290 ◽  
Author(s):  
M. ANDRECUT ◽  
S. A. KAUFFMAN ◽  
A. M. MADNI

We report the reconstruction of the topology of gene regulatory network in human tissues. The results show that the connectivity of the regulatory gene network is characterized by a scale-free distribution. This result supports the hypothesis that scale-free networks may represent the common blueprint for gene regulatory networks.


2005 ◽  
Vol 83 (1) ◽  
pp. 75-89 ◽  
Author(s):  
Angela C Cone ◽  
Robert W Zeller

Ascidians are ideally positioned taxonomically at the base of the chordate tree to provide a point of comparison for developmental regulatory mechanisms that operate among protostomes, non-chordate deuterostomes, invertebrate chordates, and vertebrates. In this review, we propose a model for the gene regulatory network that gives rise to the ascidian notochord. The purpose of this model is not to clarify all of the interactions between molecules of this network, but to provide a working schematic of the regulatory architecture that leads to the specification of endoderm and the patterning of mesoderm in ascidian embryos. We describe a series of approaches, both computational and biological, that are currently being used, or are in development, for the study of ascidian embryo gene regulatory networks. It is our belief that the tools now available to ascidian biologists, in combination with a streamlined mode of development and small genome size, will allow for more rapid dissection of developmental gene regulatory networks than in more complex organisms such as vertebrates. It is our hope that the analysis of gene regulatory networks in ascidians can provide a basic template which will allow developmental biologists to superimpose the modifications and novelties that have arisen during deuterostome evolution.


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