scholarly journals Robust dynamics in minimal hybrid models of genetic networks

2010 ◽  
Vol 368 (1930) ◽  
pp. 4961-4975 ◽  
Author(s):  
Theodore J. Perkins ◽  
Roy Wilds ◽  
Leon Glass
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Genetic Networks ◽  
Protein Molecules ◽  
Symbolic Sequences ◽  
Gene Regulatory ◽  
Logical Functions ◽  
Insight Into

Many gene-regulatory networks necessarily display robust dynamics that are insensitive to noise and stable under evolution. We propose that a class of hybrid systems can be used to relate the structure of these networks to their dynamics and provide insight into the origin of robustness. In these systems, the genes are represented by logical functions, and the controlling transcription factor protein molecules are real variables, which are produced and destroyed. As the transcription factor concentrations cross thresholds, they control the production of other transcription factors. We discuss mathematical analysis of these systems and show how the concepts of robustness and minimality can be used to generate putative logical organizations based on observed symbolic sequences. We apply the methods to control of the cell cycle in yeast.

scholarly journals Modular Evolution of DNA-Binding Preference of a Tbrain Transcription Factor Provides a Mechanism for Modifying Gene Regulatory Networks

2014 ◽  
Vol 31 (10) ◽  
pp. 2672-2688 ◽  
Author(s):  
Alys M. Cheatle Jarvela ◽  
Lisa Brubaker ◽  
Anastasia Vedenko ◽  
Anisha Gupta ◽  
Bruce A. Armitage ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Modular Evolution ◽  
Binding Preference ◽  
Gene Regulatory

scholarly journals Modeling transcriptional regulation using gene regulatory networks based on multi-omics data sources

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Neel Patel ◽  
William S. Bush
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Prediction Models ◽  
Long Distance ◽  
Chromatin Looping ◽  
Gene Regulatory ◽  
The Impact

Abstract Background Transcriptional regulation is complex, requiring multiple cis (local) and trans acting mechanisms working in concert to drive gene expression, with disruption of these processes linked to multiple diseases. Previous computational attempts to understand the influence of regulatory mechanisms on gene expression have used prediction models containing input features derived from cis regulatory factors. However, local chromatin looping and trans-acting mechanisms are known to also influence transcriptional regulation, and their inclusion may improve model accuracy and interpretation. In this study, we create a general model of transcription factor influence on gene expression by incorporating both cis and trans gene regulatory features. Results We describe a computational framework to model gene expression for GM12878 and K562 cell lines. This framework weights the impact of transcription factor-based regulatory data using multi-omics gene regulatory networks to account for both cis and trans acting mechanisms, and measures of the local chromatin context. These prediction models perform significantly better compared to models containing cis-regulatory features alone. Models that additionally integrate long distance chromatin interactions (or chromatin looping) between distal transcription factor binding regions and gene promoters also show improved accuracy. As a demonstration of their utility, effect estimates from these models were used to weight cis-regulatory rare variants for sequence kernel association test analyses of gene expression. Conclusions Our models generate refined effect estimates for the influence of individual transcription factors on gene expression, allowing characterization of their roles across the genome. This work also provides a framework for integrating multiple data types into a single model of transcriptional regulation.

Modelling Gene Regulatory Networks Using Computational Intelligence Techniques

2010 ◽  
pp. 244-265
Author(s):  
Ramesh Ram ◽  
Madhu Chetty
Keyword(s):  
Genetic Algorithm ◽  
Cell Cycle ◽  
Gene Regulatory Networks ◽  
Computational Intelligence ◽  
Regulatory Networks ◽  
Causal Model ◽  
Yeast Cell Cycle ◽  
Computational Perspective ◽  
Modelling Techniques ◽  
Gene Regulatory

This chapter presents modelling gene regulatory networks (GRNs) using probabilistic causal model and the guided genetic algorithm. The problem of modelling is explained from both a biological and computational perspective. Further, a comprehensive methodology for developing a GRN model is presented where the application of computation intelligence (CI) techniques can be seen to be significantly important in each phase of modelling. An illustrative example of the causal model for GRN modelling is also included and applied to model the yeast cell cycle dataset. The results obtained are compared for providing biological relevance to the findings which thereby underpins the CI based modelling techniques.

scholarly journals Accurate differential analysis of transcription factor activity from gene expression

2018 ◽  
Author(s):  
Viren Amin ◽  
Murat Can Cobanoglu
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Expression Data ◽  
Differential Analysis ◽  
Gene Regulatory ◽  
Context Specific ◽  
Tf Gene ◽  
Perturbation Estimation

AbstractWe present EPEE (Effector and Perturbation Estimation Engine), a method for differential analysis of transcription factor (TF) activity from gene expression data. EPEE addresses two principal challenges in the field, namely incorporating context-specific TF-gene regulatory networks, and accounting for the fact that TF activity inference is intrinsically coupled for all TFs that share targets. Our validations in well-studied immune and cancer contexts show that addressing the overlap challenge and using state-of-the-art regulatory networks enable EPEE to consistently produce accurate results. (Accessible at: https://github.com/Cobanoglu-Lab/EPEE)

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 RUNX1-EVI1 disrupts lineage determination and the cell cycle by interfering with RUNX1 and EVI1 driven gene regulatory networks

Haematologica ◽  
2020 ◽  
pp. haematol.2019.241885
Author(s):  
Sophie G. Kellaway ◽  
Peter Keane ◽  
Ella Kennett ◽  
Constanze Bonifer
Keyword(s):  
Cell Cycle ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Gene Regulatory

Using Bayesian Networks to Construct Gene Regulatory Networks from Microarray Data

2012 ◽  
pp. 1-6
Author(s):  
Ai Kung Tan ◽  
Mohd Saberi Mohamad
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Bayesian Networks ◽  
Bayesian Network ◽  
Gene Regulatory Networks ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Cell Cycle Gene ◽  
Gene Regulatory ◽  
Cell Cycle Gene Expression

In this research, Bayesian network is proposed as the model to construct gene regulatory networks from Saccharomyces cerevisiae cell-cycle gene expression dataset and Escherichia coli dataset due to its capability of handling microarray datasets with missing values. The goal of this research is to study and to understand the framework of the Bayesian networks, and then to construct gene regulatory networks from Saccharomyces cerevisiae cell-cycle gene expression dataset and Escherichia coli dataset by developing Bayesian networks using hill-climbing algorithm and Efron’s bootstrap approach and then the performance of the constructed gene networks of Saccharomyces cerevisiae are evaluated and are compared with the previously constructed sub-networks by Dejori [14]. At the end of this research, the gene networks constructed for Saccharomyces cerevisiae not only have achieved high True Positive Rate (more than 90%), but the networks constructed also have discovered more potential interactions between genes. Therefore, it can be concluded that the performance of the gene regulatory networks constructed using Bayesian networks in this research is proved to be better because it can reveal more gene relationships. Dalam penyelidikan ini, Bayesian network adalah dicadangkan sebagai model untuk membina gene regulatory networks dari kitar sel S. cerevisiae set data disebabkan keupayaannya untuk mengendali set data microarray yang mempunyai nilai-nilai yang hilang. Tujuan penyelidikan ini adalah untuk mempelajari dan memahami rekabentuk untuk Bayesian network, dan kemudian untuk membina gene regulatory networks dari data Saccharomyces cerevisiae cell-cycle gene expression dan data Escherichia coli dengan membina model Bayesian networks dengan menggunakan algoritma hill-climbing serta Efron’s bootstrap approach dan gene networks yang dibina untuk Saccharomyces cerevisiae dibandingkan dengan sub-networks yang dibina oleh Dejori [14]. Pada akhir kajian ini, gene networks yang dibina untuk Saccharomyces cerevisiae bukan sahaja telah mencapai True Positive Rate yang tinggi (lebih dari 90%), tetapi gene networks yang dibina juga telah menemui lebih banyak interaksi berpotensi antara gen. Oleh kerana itu, dapat disimpulkan bahawa prestasi gene networks yang dibina menggunakan Bayesian network dalam kajian ini adalah terbukti lebih baik kerana ia boleh mendedahkan lebih banyak hubungan antara gen.

scholarly journals Gene regulatory networks and transcription factor transcriptomics

2009 ◽  
Vol 25 ◽  
pp. S318
Author(s):  
B. Mueller-Roeber ◽  
S. Arvidsson ◽  
S. Balazadeh ◽  
L.G.G. Corrêa ◽  
P. Pérez-Rodríguez ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Gene Regulatory
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