scholarly journals Predicting synchronized gene coexpression patterns from fibration symmetries in gene regulatory networks in bacteria

2020 ◽  
Author(s):  
Ian Leifer ◽  
Mishael Sanchez ◽  
Cecilia Ishida ◽  
Hernan Makse
Keyword(s):  
Gene Expression ◽  
Gene Regulatory Networks ◽  
Network Structure ◽  
Regulatory Networks ◽  
Transcriptional Regulatory Networks ◽  
Conceptual Tool ◽  
Gene Coexpression ◽  
Expression Of Genes ◽  
Transcriptional Regulatory ◽  
Gene Regulatory

Abstract Background: Gene regulatory networks coordinate the expression of genes across physiological states and ensure a synchronized expression of genes in cellular subsystems, critical for the coherent functioning of cells. Here we address the questions whether it is possible to predict gene synchronization from network structure alone. We have recently shown that synchronized gene expression may be predicted from symmetries in the transcriptional regulatory networks (TRN) and described by the concept of symmetry fibrations. We showed that symmetry fibrations partition the genes into groups called fibers based on the symmetries of their 'input trees', the set of paths in the network through which signals can reach a gene. In idealized dynamic gene expression models, all genes in a fiber are perfectly synchronized, while less idealized models -- with gene input functions differencing between genes -- predict symmetry breaking and desynchronization. Results: To study the functional role of gene fibers and to test whether some of the fiber-induced coexpression remains in reality, we analyze gene fibrations for the transcription networks of E. coli and B. subtilis and confront them with expression data. We find approximate gene coexpression patterns consistent with symmetry fibrations with idealized gene expression dynamics. This shows that network structure alone provides useful information about gene synchronization, and suggest that gene input functions within fibers may be further streamlined by evolutionary pressures to realize a coexpression of genes. Conclusions: Thus, gene fibrations provides a sound conceptual tool to describe tunable coexpression induced by network topology and shaped by mechanistic details of gene expression.

scholarly journals Predicting synchronized gene coexpression patterns from fibration symmetries in gene regulatory networks in bacteria

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ian Leifer ◽  
Mishael Sánchez-Pérez ◽  
Cecilia Ishida ◽  
Hernán A. Makse
Keyword(s):  
Gene Expression ◽  
Gene Regulatory Networks ◽  
Network Structure ◽  
Regulatory Networks ◽  
Conceptual Tool ◽  
E Coli ◽  
Gene Coexpression ◽  
Expression Of Genes ◽  
Gene Expression Dynamics ◽  
Gene Regulatory

Abstract Background Gene regulatory networks coordinate the expression of genes across physiological states and ensure a synchronized expression of genes in cellular subsystems, critical for the coherent functioning of cells. Here we address the question whether it is possible to predict gene synchronization from network structure alone. We have recently shown that synchronized gene expression can be predicted from symmetries in the gene regulatory networks described by the concept of symmetry fibrations. We showed that symmetry fibrations partition the genes into groups called fibers based on the symmetries of their ’input trees’, the set of paths in the network through which signals can reach a gene. In idealized dynamic gene expression models, all genes in a fiber are perfectly synchronized, while less idealized models—with gene input functions differencing between genes—predict symmetry breaking and desynchronization. Results To study the functional role of gene fibers and to test whether some of the fiber-induced coexpression remains in reality, we analyze gene fibrations for the gene regulatory networks of E. coli and B. subtilis and confront them with expression data. We find approximate gene coexpression patterns consistent with symmetry fibrations with idealized gene expression dynamics. This shows that network structure alone provides useful information about gene synchronization, and suggest that gene input functions within fibers may be further streamlined by evolutionary pressures to realize a coexpression of genes. Conclusions Thus, gene fibrations provide a sound conceptual tool to describe tunable coexpression induced by network topology and shaped by mechanistic details of gene expression.

What are Gene Regulatory Networks?

2010 ◽  
pp. 1-27 ◽  
Author(s):  
Alberto de la Fuente
Keyword(s):  
Gene Expression ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Network Models ◽  
Transcriptional Regulatory Networks ◽  
Biochemical Processes ◽  
Transcriptional Regulatory ◽  
Biochemical Systems ◽  
Gene Regulatory

This book deals with algorithms for inferring and analyzing Gene Regulatory Networks using mainly gene expression data. What precisely are the Gene Regulatory Networks that are inferred by such algorithms from this type of data? There is still much confusion in the current literature and it is important to start a book about computational methods for Gene Regulatory Networks with a definition that is as unambiguous as possible. In this chapter, I provide a definition and try to clearly explain what Gene Regulatory Networks are in terms of the underlying biochemical processes. To do the latter in a formal way, I will use a linear approximation to the in general non-linear kinetics underlying interactions in biochemical systems and show how a biochemical system can be ‘condensed’ into the more compact description of Gene Regulatory Networks. Important differences between the defined Gene Regulatory Networks and other network models for gene regulation, such as Transcriptional Regulatory Networks and Co-Expression Networks, will be highlighted.

scholarly journals Neural Gene Network Constructor: A Neural Based Model for Reconstructing Gene Regulatory Network

2019 ◽  
Author(s):  
Zhang Zhang ◽  
Lifei Wang ◽  
Shuo Wang ◽  
Ruyi Tao ◽  
Jingshu Xiao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulatory Network ◽  
Gene Expression Data ◽  
Gene Regulatory Networks ◽  
Network Structure ◽  
Regulatory Network ◽  
Gene Network ◽  
Regulatory Networks ◽  
Expression Data ◽  
Gene Regulatory

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.

Condensing Biochemistry into Gene Regulatory Networks

2014 ◽  
Vol 4 (3) ◽  
pp. 1-25
Author(s):  
Alberto de la Fuente
Keyword(s):  
Gene Regulation ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Network Models ◽  
Transcriptional Regulatory Networks ◽  
Modern Biology ◽  
Genome Wide ◽  
Transcriptional Regulatory ◽  
Biochemical Systems ◽  
Gene Regulatory

Gene Regulatory Networks are models of gene regulation. Inferring such model from genome-wide gene-expression measurements is one of the key challenges in modern biology, and a large number of algorithms have been proposed for this task. As there is still much confusion in the current literature as to what precisely Gene Regulatory Networks are, it is important to provide a definition that is as unambiguous as possible. In this paper the author provides such a definition and explain what Gene Regulatory Networks are in terms of the underlying biochemical processes. The author will use a linear approximation to the in general non-linear kinetics underlying interactions in biochemical systems and show how a biochemical system can be ‘condensed' into a more compact description, i.e. Gene Regulatory Networks. Important differences between the defined Gene Regulatory Networks and other network models for gene regulation, i.e. Transcriptional Regulatory Networks and Co-Expression Networks, are also discussed.

scholarly journals An Integrated Database of Small RNAs and Their Interplay With Transcriptional Gene Regulatory Networks in Corynebacteria

2021 ◽  
Vol 12 ◽  
Author(s):  
Mariana Teixeira Dornelles Parise ◽  
Doglas Parise ◽  
Flavia Figueira Aburjaile ◽  
Anne Cybelle Pinto Gomide ◽  
Rodrigo Bentes Kato ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Small Rnas ◽  
Regulatory Networks ◽  
Transcriptional Regulatory Networks ◽  
Bacterial Gene ◽  
Bacterial Gene Expression ◽  
Transcriptional Regulatory ◽  
Animal Pathogens ◽  
Gene Regulatory

Small RNAs (sRNAs) are one of the key players in the post-transcriptional regulation of bacterial gene expression. These molecules, together with transcription factors, form regulatory networks and greatly influence the bacterial regulatory landscape. Little is known concerning sRNAs and their influence on the regulatory machinery in the genus Corynebacterium, despite its medical, veterinary and biotechnological importance. Here, we expand corynebacterial regulatory knowledge by integrating sRNAs and their regulatory interactions into the transcriptional regulatory networks of six corynebacterial species, covering four human and animal pathogens, and integrate this data into the CoryneRegNet database. To this end, we predicted sRNAs to regulate 754 genes, including 206 transcription factors, in corynebacterial gene regulatory networks. Amongst them, the sRNA Cd-NCTC13129-sRNA-2 is predicted to directly regulate ydfH, which indirectly regulates 66 genes, including the global regulator glxR in C. diphtheriae. All of the sRNA-enriched regulatory networks of the genus Corynebacterium have been made publicly available in the newest release of CoryneRegNet(www.exbio.wzw.tum.de/coryneregnet/) to aid in providing valuable insights and to guide future experiments.

scholarly journals Programmatic access to bacterial regulatory networks with regutools

2020 ◽  
Vol 36 (16) ◽  
pp. 4532-4534
Author(s):  
Joselyn Chávez ◽  
Carmina Barberena-Jonas ◽  
Jesus E Sotelo-Fonseca ◽  
José Alquicira-Hernández ◽  
Heladia Salgado ◽  
...  
Keyword(s):  
Data Structures ◽  
Gene Regulatory Networks ◽  
Binding Sites ◽  
Regulatory Networks ◽  
R Package ◽  
Transcriptional Regulatory Networks ◽  
Dna Binding Sites ◽  
Transcriptional Regulatory ◽  
Gene Regulatory ◽  
Programmatic Access

Abstract Summary RegulonDB has collected, harmonized and centralized data from hundreds of experiments for nearly two decades and is considered a point of reference for transcriptional regulation in Escherichia coli K12. Here, we present the regutools R package to facilitate programmatic access to RegulonDB data in computational biology. regutools gives researchers the possibility of writing reproducible workflows with automated queries to RegulonDB. The regutools package serves as a bridge between RegulonDB data and the Bioconductor ecosystem by reusing the data structures and statistical methods powered by other Bioconductor packages. We demonstrate the integration of regutools with Bioconductor by analyzing transcription factor DNA binding sites and transcriptional regulatory networks from RegulonDB. We anticipate that regutools will serve as a useful building block in our progress to further our understanding of gene regulatory networks. Availability and implementation regutools is an R package available through Bioconductor at bioconductor.org/packages/regutools.

scholarly journals Programmatic access to bacterial regulatory networks with regutools

2020 ◽  
Author(s):  
Joselyn Chávez ◽  
Carmina Barberena-Jonas ◽  
Jesus E. Sotelo-Fonseca ◽  
José Alquicira-Hernández ◽  
Heladia Salgado ◽  
...  
Keyword(s):  
Data Structures ◽  
Gene Regulatory Networks ◽  
Binding Sites ◽  
Regulatory Networks ◽  
Transcriptional Regulatory Networks ◽  
Link Type ◽  
Dna Binding Sites ◽  
Transcriptional Regulatory ◽  
Gene Regulatory ◽  
Programmatic Access

AbstractSummaryRegulonDB has collected, harmonized and centralized data from hundreds of experiments for nearly two decades and is considered a point of reference for transcriptional regulation in Escherichia coli K12. Here, we present the regutools R package to facilitate programmatic access to RegulonDB data in computational biology. regutools gives researchers the possibility of writing reproducible workflows with automated queries to RegulonDB. The regutools package serves as a bridge between RegulonDB data and the Bioconductor ecosystem by reusing the data structures and statistical methods powered by other Bioconductor packages. We demonstrate the integration of regutools with Bioconductor by analyzing transcription factor DNA binding sites and transcriptional regulatory networks from RegulonDB. We anticipate that regutools will serve as a useful building block in our progress to further our understanding of gene regulatory networks.Availability and Implementationregutools is an R package available through Bioconductor at bioconductor.org/packages/regutools.Contactgithub.com/ComunidadBioInfo/regutools, [email protected], [email protected].

scholarly journals GATA-targeted compounds modulate cardiac subtype cell differentiation in dual reporter stem cell line

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mika J. Välimäki ◽  
Robert S. Leigh ◽  
Sini M. Kinnunen ◽  
Alexander R. March ◽  
Ana Hernández de Sande ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Reporter Gene ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cell Fate Decisions ◽  
Dual Reporter ◽  
Gene Regulatory ◽  
Reporter Gene Assays

AbstractBackgroundPharmacological modulation of cell fate decisions and developmental gene regulatory networks holds promise for the treatment of heart failure. Compounds that target tissue-specific transcription factors could overcome non-specific effects of small molecules and lead to the regeneration of heart muscle following myocardial infarction. Due to cellular heterogeneity in the heart, the activation of gene programs representing specific atrial and ventricular cardiomyocyte subtypes would be highly desirable. Chemical compounds that modulate atrial and ventricular cell fate could be used to improve subtype-specific differentiation of endogenous or exogenously delivered progenitor cells in order to promote cardiac regeneration.MethodsTranscription factor GATA4-targeted compounds that have previously shown in vivo efficacy in cardiac injury models were tested for stage-specific activation of atrial and ventricular reporter genes in differentiating pluripotent stem cells using a dual reporter assay. Chemically induced gene expression changes were characterized by qRT-PCR, global run-on sequencing (GRO-seq) and immunoblotting, and the network of cooperative proteins of GATA4 and NKX2-5 were further explored by the examination of the GATA4 and NKX2-5 interactome by BioID. Reporter gene assays were conducted to examine combinatorial effects of GATA-targeted compounds and bromodomain and extraterminal domain (BET) inhibition on chamber-specific gene expression.ResultsGATA4-targeted compounds 3i-1000 and 3i-1103 were identified as differential modulators of atrial and ventricular gene expression. More detailed structure-function analysis revealed a distinct subclass of GATA4/NKX2-5 inhibitory compounds with an acetyl lysine-like domain that contributed to ventricular cells (%Myl2-eGFP+). Additionally, BioID analysis indicated broad interaction between GATA4 and BET family of proteins, such as BRD4. This indicated the involvement of epigenetic modulators in the regulation of GATA-dependent transcription. In this line, reporter gene assays with combinatorial treatment of 3i-1000 and the BET bromodomain inhibitor (+)-JQ1 demonstrated the cooperative role of GATA4 and BRD4 in the modulation of chamber-specific cardiac gene expression.ConclusionsCollectively, these results indicate the potential for therapeutic alteration of cell fate decisions and pathological gene regulatory networks by GATA4-targeted compounds modulating chamber-specific transcriptional programs in multipotent cardiac progenitor cells and cardiomyocytes. The compound scaffolds described within this study could be used to develop regenerative strategies for myocardial regeneration.

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