Search results for "Gene Regulatory Network"

Cell-cell bioelectrical interactions and local heterogeneities in genetic networks: a model for the stabilization of single-cell states and multicell…

2018

Genetic networks operate in the presence of local heterogeneities in single-cell transcription and translation rates. Bioelectrical networks and spatio-temporal maps of cell electric potentials can influence multicellular ensembles. Could cell-cell bioelectrical interactions mediated by intercellular gap junctions contribute to the stabilization of multicellular states against local genetic heterogeneities? We theoretically analyze this question on the basis of two well-established experimental facts: (i) the membrane potential is a reliable read-out of the single-cell electrical state and (ii) when the cells are coupled together, their individual cell potentials can be influenced by ensemb…

2016

AbstractShort posterior ciliary arteries (sPCA) provide the major blood supply to the optic nerve head. Emerging evidence has linked structural and functional anomalies of sPCA to the pathogenesis of several ocular disorders that cause varying degrees of visual loss, particularly anterior ischaemic optic neuropathy and glaucoma. Although the functional relevance of this vascular bed is well-recognized, the proteome of sPCA remains uncharacterized. Since the porcine ocular system closely resembles that of the human’s and is increasingly employed in translational ophthalmic research, this study characterized the proteome of porcine sPCA employing the mass spectrometry-based proteomics strateg…

Increased liver carcinogenesis and enrichment of stem cell properties in livers of Dickkopf 2 (Dkk2) deleted mice.

2013

// Thorsten Maass 1 , Jens Marquardt 2 , Ju-Seog Lee 3 , Markus Krupp 4 , Peter Scholz-Kreisel 2 , Carolin Mogler 5 , Peter Schirmacher 5 , Martina Muller 1 , Heiner Westphal 6 , Peter R. Galle 2 , Andreas Teufel 1 1 Department of Internal Medicine I, University of Regensburg, Regensburg, Germany 2 I. Department of Medicine, University Medical Center Mainz, Mainz, Germany 3 Cancer Biology Program, MD Anderson Cancer Center, Houston, TX, USA 4 Department of Informatics, Johannes Gutenberg University Mainz, Mainz, Germany 5 Institute of Pathology, University of Heidelberg, Heidelberg, Germany 6 Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Develop…

Regulatory network analysis in estradiol-treated human endothelial cells.

2021

Background/Aims: Estrogen has been reported to have beneficial effects on vascular biology through direct actions on endothelium. Together with transcription factors, miRNAs are the major drivers of gene expression and signaling networks. The objective of this study was to identify a com-prehensive regulatory network (miRNA-transcription factor-downstream genes) that controls the transcriptomic changes observed in endothelial cells exposed to estradiol. Methods: miR-NA/mRNA interactions were assembled using our previous microarray data of human umbilical vein endothelial cells (HUVEC) treated with 17ß- Estradiol (E2) (1 nmol/lL, 24 h). miRNA--mRNA pairings and their associated canonical pat…

A Methodological Framework to Discover Pharmacogenomic Interactions Based on Random Forests

2021

The identification of genomic alterations in tumor tissues, including somatic mutations, deletions, and gene amplifications, produces large amounts of data, which can be correlated with a diversity of therapeutic responses. We aimed to provide a methodological framework to discover pharmacogenomic interactions based on Random Forests. We matched two databases from the Cancer Cell Line Encyclopaedia (CCLE) project, and the Genomics of Drug Sensitivity in Cancer (GDSC) project. For a total of 648 shared cell lines, we considered 48,270 gene alterations from CCLE as input features and the area under the dose-response curve (AUC) for 265 drugs from GDSC as the outcomes. A three-step reduction t…

2017

Strategies for promoting neural regeneration are hindered by the difficulty of manipulating desired neural fates in the brain without complex genetic methods. The subventricular zone (SVZ) is the largest germinal zone of the forebrain and is responsible for the lifelong generation of interneuron subtypes and oligodendrocytes. Here, we have performed a bioinformatics analysis of the transcriptome of dorsal and lateral SVZ in early postnatal mice, including neural stem cells (NSCs) and their immediate progenies, which generate distinct neural lineages. We identified multiple signaling pathways that trigger distinct downstream transcriptional networks to regulate the diversity of neural cells …

The ribosome assembly gene network is controlled by the feedback regulation of transcription elongation

2017

Ribosome assembly requires the concerted expression of hundreds of genes, which are transcribed by all three nuclear RNA polymerases. Transcription elongation involves dynamic interactions between RNA polymerases and chromatin. We performed a synthetic lethal screening in Saccharomyces cerevisiae with a conditional allele of SPT6, which encodes one of the factors that facilitates this process. Some of these synthetic mutants corresponded to factors that facilitate pre-rRNA processing and ribosome biogenesis. We found that the in vivo depletion of one of these factors, Arb1, activated transcription elongation in the set of genes involved directly in ribosome assembly. Under these depletion c…

Identification of microRNAS differentially regulated by water deficit in relation to mycorrhizal treatment in wheat.

2019

Arbuscular mycorrhizal fungi (AMF) are soil microrganisms that establish symbiosis with plants positively influencing their resistance to abiotic stresses. The aim of this work was to identify wheat miRNAs differentially regulated by water deficit conditions in presence or absence of AMF treatment. Small RNA libraries were constructed for both leaf and root tissues considering four conditions: control (irrigated) or water deficit in presence/absence of mycorrhizal (AMF) treatment. A total of 12 miRNAs were significantly regulated by water deficit in leaves: five in absence and seven in presence of AMF treatment. In roots, three miRNAs were water deficit-modulated in absence of mycorrhizal t…

L1-Penalized Censored Gaussian Graphical Model

2018

Graphical lasso is one of the most used estimators for inferring genetic networks. Despite its diffusion, there are several fields in applied research where the limits of detection of modern measurement technologies make the use of this estimator theoretically unfounded, even when the assumption of a multivariate Gaussian distribution is satisfied. Typical examples are data generated by polymerase chain reactions and flow cytometer. The combination of censoring and high-dimensionality make inference of the underlying genetic networks from these data very challenging. In this article, we propose an $\ell_1$-penalized Gaussian graphical model for censored data and derive two EM-like algorithm…

Model selection for factorial Gaussian graphical models with an application to dynamic regulatory networks.

2016

Abstract Factorial Gaussian graphical Models (fGGMs) have recently been proposed for inferring dynamic gene regulatory networks from genomic high-throughput data. In the search for true regulatory relationships amongst the vast space of possible networks, these models allow the imposition of certain restrictions on the dynamic nature of these relationships, such as Markov dependencies of low order – some entries of the precision matrix are a priori zeros – or equal dependency strengths across time lags – some entries of the precision matrix are assumed to be equal. The precision matrix is then estimated by l 1-penalized maximum likelihood, imposing a further constraint on the absolute value…