IRP1443REG - Ralstonia solanacearum GMI1000 Virulence regulatory network
Ontology highlight
ABSTRACT:
SUBMITTER: 
Ludovic Cottret
PROVIDER: MODEL1710170000 | BioModels | 2023-11-10
REPOSITORIES: BioModels
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| MODEL1710170000?filename=MODEL1710170000_url.xml | Xml |
Items per page: 5 1 - 1 of 1 |
Publications
Control of primary metabolism by a virulence regulatory network promotes robustness in a plant pathogen.
Peyraud Rémi R Cottret Ludovic L Marmiesse Lucas L Genin Stéphane S
Nature communications 20180129 1
Robustness is a key system-level property of living organisms to maintain their functions while tolerating perturbations. We investigate here how a regulatory network controlling multiple virulence factors impacts phenotypic robustness of a bacterial plant pathogen. We reconstruct a cell-scale model of Ralstonia solanacearum connecting a genome-scale metabolic network, a virulence macromolecule network, and a virulence regulatory network, which includes 63 regulatory components. We develop in si ...[more]
Similar Datasets
Project description:Methylotrophy is the ability of organisms to grow at the expense of reduced one-carbon compounds such as methanol or methane. Here, we used transposon sequencing combining hyper-saturated transposon mutagenesis with high-throughput sequencing to define the essential methylotrophy genome of Methylobacterium extorquens PA1, a model methylotroph. To distinguish genomic regions required for growth only on methanol from general required genes, we contrasted growth on methanol with growth on succinate, a non-methylotrophic reference substrate. About 500'000 insertions were mapped for each condition, resulting in a median insertion distance of 5 base pairs. We identified 147 genes and 76 genes as specific for growth on methanol and succinate, respectively, and a set of 590 genes as required under both growth conditions. For the integration of metabolic functions, we reconstructed a genome-scale metabolic model and performed in silico essentiality analysis. In total, the approach uncovered 95 previously not described genes as crucial for methylotrophy, including genes involved in respiration, carbon metabolism, transport, and regulation. Strikingly, regardless of the absence of the Calvin cycle in the methylotroph, the screen led to the identification of the gene for phosphoribulokinase as essential during growth on methanol but not on succinate. Genetic experiments in addition to metabolomics and proteomics revealed that phosphoribulokinase serves a key regulatory function. Our data support a model according to which ribulose-1,5 bisphosphate is an essential metabolite that induces a transcriptional regulator driving one-carbon assimilation.
2017-07-11 | PXD006834 | Pride
Project description:Number of publications show that intestinal microflora vesicles secretion is essential for the maintaining homeostasis. Conducted comprehensive genomic, transcriptomic and proteomic studies of vesicles determine the nature and the basic mechanisms of bacterial influence to the host. The role of the vesicles to a greater extent is defined as carriers of virulence factors or enzymes determining the nutritional function. In addition some bacterial vesicles have a special mission. B.fragilis vesicles are providing anti-inflammatory effect on the colon immune cells. However there is no information about possible role of vesicles secreted by ETBF, contributing bowel disease development and colon cancer. To determine possible effects of ETBF vesicles to the host compared with NTBF, we performed comprehensive proteome and for the first time metabolome analysis and reconstructed pathways for vesicles of both strains with subsequent confirmation of the activity of one of the main pathway by fluxome analysis. A detailed analysis of the vesicles allowed us to discover a new quality of ETBF vesicles as intelligent systems capable of absorbing and processing of exogenous substrates. We believe that this property allows them to maintain stability for a long time and implement mechanisms of pathogenicity.
2017-11-13 | PXD005255 | Pride
Project description:The proteins from the Fanconi Anemia (FA) pathway of DNA repair maintain DNA replication fork integrity by preventing the unscheduled degradation of nascent DNA at regions of stalled replication forks. Here, we ask if the bacterial pathogen H. pylori exploits the fork stabilisation machinery to generate double stand breaks (DSBs) and genomic instability. Specifically, we study if the H. pylori virulence factor CagA generates host genomic DSBs through replication fork destabilisation and collapse. An inducible gastric cancer model was used to examine global CagA-dependent transcriptomic and proteomic alterations, using RNA sequencing and SILAC-based mass spectrometry, respectively. The transcriptional alterations were confirmed in gastric cancer cell lines infected with H. pylori. Functional analysis was performed using chromatin fractionation, pulsed-field gel electrophoresis (PFGE), and single molecule DNA replication/repair fiber assays. We found a core set of 31 DNA repair factors including the FA genes FANCI, FANCD2, BRCA1, and BRCA2 that were downregulated following CagA expression. H. pylori infection of gastric cancer cell lines showed downregulation of the aforementioned FA genes in a CagA-dependent manner. Consistent with FA pathway downregulation, chromatin purification studies revealed impaired levels of Rad51 but higher recruitment of the nuclease MRE11 on the chromatin of CagA-expressing cells, suggesting impaired fork protection. In line with the above data, fibre assays revealed higher fork degradation, lower fork speed, daughter strands gap accumulation, and impaired re-start of replication forks in the presence of CagA, indicating compromised genome stability. By downregulating the expression of key DNA repair genes such as FANCI, FANCD2, BRCA1, and BRCA2, H. pylori CagA compromises host replication fork stability and induces DNA DSBs through fork collapse. These data unveil an intriguing example of a bacterial virulence factor that induces genomic instability by interfering with the host replication fork stabilisation machinery.
2022-02-22 | PXD031168 | Pride
Project description:Reed2003 - Genome-scale metabolic network of
Escherichia coli (iJR904)
This model is described in the article:
An expanded genome-scale
model of Escherichia coli K-12 (iJR904 GSM/GPR).
Reed JL, Vo TD, Schilling CH,
Palsson BO.
Genome Biol. 2003; 4(9): R54
Abstract:
BACKGROUND: Diverse datasets, including genomic,
transcriptomic, proteomic and metabolomic data, are becoming
readily available for specific organisms. There is currently a
need to integrate these datasets within an in silico modeling
framework. Constraint-based models of Escherichia coli K-12
MG1655 have been developed and used to study the bacterium's
metabolism and phenotypic behavior. The most comprehensive E.
coli model to date (E. coli iJE660a GSM) accounts for 660 genes
and includes 627 unique biochemical reactions. RESULTS: An
expanded genome-scale metabolic model of E. coli (iJR904
GSM/GPR) has been reconstructed which includes 904 genes and
931 unique biochemical reactions. The reactions in the expanded
model are both elementally and charge balanced. Network gap
analysis led to putative assignments for 55 open reading frames
(ORFs). Gene to protein to reaction associations (GPR) are now
directly included in the model. Comparisons between predictions
made by iJR904 and iJE660a models show that they are generally
similar but differ under certain circumstances. Analysis of
genome-scale proton balancing shows how the flux of protons
into and out of the medium is important for maximizing cellular
growth. CONCLUSIONS: E. coli iJR904 has improved capabilities
over iJE660a. iJR904 is a more complete and chemically accurate
description of E. coli metabolism than iJE660a. Perhaps most
importantly, iJR904 can be used for analyzing and integrating
the diverse datasets. iJR904 will help to outline the
genotype-phenotype relationship for E. coli K-12, as it can
account for genomic, transcriptomic, proteomic and fluxomic
data simultaneously.
This model is hosted on
BioModels Database
and identified by:
MODEL1507180060.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2015-07-30 | MODEL1507180060 | BioModels
Project description:Illuminating the precise stepwise genetic programs directing cardiac development provides insights into the mechanisms of congenital heart disease and strategies for cardiac regenerative therapies. Here, we integrated in vitro and in vivo human single-cell multi-omic studies with high-throughput functional genomic screening to reveal dynamic, cardiac-specific gene regulatory networks and transcriptional regulators during human cardiomyocyte development. Interrogating developmental trajectories reconstructed from single-cell data unexpectedly revealed divergent cardiomyocyte lineages with distinct gene programs based on developmental signaling pathways. High-throughput functional genomic screens identified key transcription factors from inferred gene regulatory networks (GRNs) that were functionally relevant for cardiomyocyte lineages derived from each pathway. Notably, we discovered a critical HSF1-mediated cardiometabolic GRN controlling cardiac mitochondrial/metabolic function and cell survival, also observed in fetal human cardiomyocytes. Overall, these multi-modal genomic studies enabled the systematic discovery and validation of coordinated gene regulatory networks and transcriptional regulators controlling the development of distinct human cardiomyocyte populations.
2024-09-06 | GSE245499 | GEO
Project description:Transcriptional changes occur presymptomatically and throughout Huntington’s disease (HD), motivating the study of transcriptional regulatory networks (TRNs) in HD. We reconstructed a genome-scale model for the target genes of 718 transcription factors (TFs) in the mouse striatum by integrating a model of genomic binding sites with transcriptome profiling of striatal tissue from HD mouse models. We identified 48 differentially expressed TF-target gene modules associated with age- and CAG repeat length-dependent gene expression changes in Htt CAG knock-in mouse striatum, and replicated many of these associations in independent transcriptomic and proteomic datasets. 13 of 48 of these predicted TF-target gene modules were also differentially expressed in striatal tissue from human disease. We experimentally validated a specific model prediction that SMAD3 regulates HD-related gene expression changes using chromatin immunoprecipitation and deep sequencing (ChIP-seq) of mouse striatum. We found CAG repeat length-dependent changes in the genomic occupancy of SMAD3 and confirmed our model’s prediction that many SMAD3 target genes are down-regulated early in HD.
2018-02-01 | GSE88775 | GEO
Project description:We combined phenotypic and genomic assays to provide insight into its role in this pathogen. RpoN was essential for Y. pseudotuberculosis virulence in mice, and in vitro functional assays showed that it controls biofilm formation and motility. Mapping of genome-wide associations of Y. pseudotuberculosis RpoN identified an RpoN-binding motif at 103 inter- and intragenic sites located on both the sense and anti-sense strands. Transcriptomic analysis of bacteria lacking rpoN showed a large impact on gene expression, including down-regulation of genes encoding proteins involved in flagellar assembly, chemotaxis, and quorum sensing. There were also clear indications of cross talk with other sigma factors, together with indirect effects due to altered expression of other regulators. Matching differential gene expression with peak binding locations implicated around 130 genes or operons potentially activated or repressed by RpoN
2020-08-04 | GSE155606 | GEO
Project description:We combined phenotypic and genomic assays to provide insight into its role in this pathogen. RpoN was essential for Y. pseudotuberculosis virulence in mice, and in vitro functional assays showed that it controls biofilm formation and motility. Mapping of genome-wide associations of Y. pseudotuberculosis RpoN identified an RpoN-binding motif at 103 inter- and intragenic sites located on both the sense and anti-sense strands Transcriptomic analysis of bacteria lacking rpoN showed a large impact on gene expression, including down-regulation of genes encoding proteins involved in flagellar assembly, chemotaxis, and quorum sensing There were also clear indications of cross talk with other sigma factors, together with indirect effects due to altered expression of other regulators. Matching differential gene expression with peak binding locations implicated around 130 genes or operons potentially activated or repressed by RpoN
2020-08-04 | GSE155607 | GEO
Project description:Background and Aims Small intestinal neuroendocrine tumours (SINETs) are the commonest malignancy of the small intestine; however underlying pathogenic mechanisms remain poorly characterised. Whole genome and exome sequencing has demonstrated that SINETs are mutationally quiet with the most frequent known mutation in the cyclin dependent kinase inhibitor 1B gene (CDKN1B) occurring in only ~8% of tumours, suggesting that alternative mechanisms may drive tumourigenesis. The aim of this study is to perform genome-wide molecular profiling of SINETs in order to identify pathogenic drivers based on molecular profiling. This study represents the largest unbiased integrated genomic, epigenomic, and transcriptomic analysis undertaken in this tumour type. Methods Here we present data from integrated molecular analysis of SINETs (n=97) including whole exome or targeted CDKN1B sequencing (n=29), HumanMethylation450 BeadChip (Illumina) array profiling (n=69), methylated DNA immunoprecipitation sequencing (n=16), copy number variance analysis (n=47) and Whole Genome-DASL (Illumina) expression array profiling (n=43). Results Based on molecular profiling SINETs can be classified in to three groups which demonstrate significantly different progression-free survival after resection of primary tumour (not reached at 10 years vs 56 months vs 21 months, p=0.04). Epimutations were found at a recurrence rate of up to 85% and 21 epigenetically dysregulated genes were identified, including CDX1 (86%), CELSR3 (84%), FBP1 (84%) and GIPR (74%). Conclusions This is the first comprehensive integrated molecular analysis of SINETs. We have demonstrated that these tumours are highly epigenetically dysregulated. Furthermore, we have identified novel molecular subtypes with significant impact on progression free survival. Background and Aims Small intestinal neuroendocrine tumours (SINETs) are the commonest malignancy of the small intestine; however underlying pathogenic mechanisms remain poorly characterised. Whole genome and exome sequencing has demonstrated that SINETs are mutationally quiet with the most frequent known mutation in the cyclin dependent kinase inhibitor 1B gene (CDKN1B) occurring in only ~8% of tumours, suggesting that alternative mechanisms may drive tumourigenesis. The aim of this study is to perform genome-wide molecular profiling of SINETs in order to identify pathogenic drivers based on molecular profiling. This study represents the largest unbiased integrated genomic, epigenomic, and transcriptomic analysis undertaken in this tumour type. Methods Here we present data from integrated molecular analysis of SINETs (n=97) including whole exome or targeted CDKN1B sequencing (n=29), HumanMethylation450 BeadChip (Illumina) array profiling (n=69), methylated DNA immunoprecipitation sequencing (n=16), copy number variance analysis (n=47) and Whole Genome-DASL (Illumina) expression array profiling (n=43). Results Based on molecular profiling SINETs can be classified in to three groups which demonstrate significantly different progression-free survival after resection of primary tumour (not reached at 10 years vs 56 months vs 21 months, p=0.04). Epimutations were found at a recurrence rate of up to 85% and 21 epigenetically dysregulated genes were identified, including CDX1 (86%), CELSR3 (84%), FBP1 (84%) and GIPR (74%). Conclusions This is the first comprehensive integrated molecular analysis of SINETs. We have demonstrated that these tumours are highly epigenetically dysregulated. Furthermore, we have identified novel molecular subtypes with significant impact on progression free survival. This study included 97 tumour samples from 85 individuals, this included both primary and metastatic tumour samples. 25 normal small intestinal samples were analysed.
2016-07-03 | E-GEOD-73832 | biostudies-arrayexpress
Project description:<p>Studies have emphasized the importance of disease-associated microorganisms in perturbed communities, however, the protective roles of commensals are largely under recognized and poorly understood. Using acne as a model disease, we investigated the determinants of the overall virulence property of the skin microbiota when disease- and health-associated organisms coexist in the community. By ultra-deep metagenomic shotgun sequencing, we revealed higher relative abundances of propionibacteria and Propionibacterium acnes phage in healthy skin. In acne patients, the microbiome composition at the species level and at P. acnes strain level was more diverse than in healthy individuals, with enriched virulence-associated factors and reduced abundance of metabolic synthesis genes. Based on the abundance profiles of the metagenomic elements, we constructed a quantitative prediction model, which classified the clinical states of the host skin with high accuracy in both our study cohort (85%) and an independent sample set (86%). Our results suggest that the balance between metagenomic elements, not the mere presence of disease-associated strains, shapes the overall virulence property of the skin microbiota. This study provides new insights into the microbial mechanism of acne pathogenesis and suggests probiotic and phage therapies as potential acne treatments to modulate the skin microbiota and to maintain skin health.</p>
| phs001655 | dbGaP