{"database":"FAIRDOMHub","file_versions":[],"scores":null,"additional":{"omics_type":["Models"],"submitter":["Guido Sanguinetti"],"full_dataset_link":["https://fairdomhub.org/models/102?version=1"],"ModelFormat":[""],"submitter_affiliation":["University of Edinburgh"],"repository":["FAIRDOMHub"],"pubmed_abstract":["Oxygen availability is the major determinant of the metabolic modes adopted by Escherichia coli. Although much is known about E. coli gene expression and metabolism under fully aerobic and anaerobic conditions, the intermediate oxygen tensions that are encountered in natural niches are understudied. Here, for the first time, the transcript profiles of E. coli K-12 across the physiologically significant range of oxygen availabilities are described. These suggested a progressive switch to aerobic respiratory metabolism and a remodeling of the cell envelope as oxygen availability increased. The transcriptional responses were consistent with changes in the abundance of cytochrome bd and bo' and the outer membrane protein OmpW. The observed transcript and protein profiles result from changes in the activities of regulators that respond to oxygen itself or to metabolic and environmental signals that are sensitive to oxygen availability (aerobiosis). A probabilistic model (TFInfer) was used to predict the activity of the indirect oxygen-sensing two-component system ArcBA across the aerobiosis range. The model implied that the activity of the regulator ArcA correlated with aerobiosis but not with the redox state of the ubiquinone pool, challenging the idea that ArcA activity is inhibited by oxidized ubiquinone. The amount of phosphorylated ArcA correlated with the predicted ArcA activities and with aerobiosis, suggesting that fermentation product-mediated inhibition of ArcB phosphatase activity is the dominant mechanism for regulating ArcA activity under the conditions used here.","Understanding gene regulation requires knowledge of changes in transcription factor (TF) activities. Simultaneous direct measurement of numerous TF activities is currently impossible. Nevertheless, statistical approaches to infer TF activities have yielded non-trivial and verifiable predictions for individual TFs. Here, global statistical modelling identifies changes in TF activities from transcript profiles of Escherichia coli growing in stable (fixed oxygen availabilities) and dynamic (changing oxygen availability) environments. A core oxygen-responsive TF network, supplemented by additional TFs acting under specific conditions, was identified. The activities of the cytoplasmic oxygen-responsive TF, FNR, and the membrane-bound terminal oxidases implied that, even on the scale of the bacterial cell, spatial effects significantly influence oxygen-sensing. Several transcripts exhibited asymmetrical patterns of abundance in aerobic to anaerobic and anaerobic to aerobic transitions. One of these transcripts, ndh, encodes a major component of the aerobic respiratory chain and is regulated by oxygen-responsive TFs ArcA and FNR. Kinetic modelling indicated that ArcA and FNR behaviour could not explain the ndh transcript profile, leading to the identification of another TF, PdhR, as the source of the asymmetry. Thus, this approach illustrates how systematic examination of regulatory responses in stable and dynamic environments yields new mechanistic insights into adaptive processes.","<h4>Summary</h4>TFInfer is a novel open access, standalone tool for genome-wide inference of transcription factor activities from gene expression data. Based on an earlier MATLAB version, the software has now been extended in a number of ways. It has been significantly optimised in terms of performance, and it was given novel functionality, by allowing the user to model both time series and data from multiple independent conditions. With a full documentation and intuitive graphical user interface, together with an in-built data base of yeast and Escherichia coli transcription factors, the software does not require any mathematical or computational expertise to be used effectively.<h4>Availability</h4>http://homepages.inf.ed.ac.uk/gsanguin/TFInfer.html<h4>Contact</h4>gsanguin@staffmail.ed.ac.uk<h4>Supplementary information</h4>Supplementary data are available at Bioinformatics online."],"pubmed_title":["Transcript profiling and inference of Escherichia coli K-12 ArcA activity across the range of physiologically relevant oxygen concentrations.","Systems analysis of transcription factor activities in environments with stable and dynamic oxygen concentrations.","TFInfer: a tool for probabilistic inference of transcription factor activities."],"pubmed_authors":["Asif H M Shahzad HM, Rolfe Matthew D MD, Green Jeff J, Lawrence Neil D ND, Rattray Magnus M, Sanguinetti Guido G","Rolfe Matthew D MD, Ocone Andrea A, Stapleton Melanie R MR, Hall Simon S, Trotter Eleanor W EW, Poole Robert K RK, Sanguinetti Guido G, Green Jeffrey J","Rolfe Matthew D MD, Ter Beek Alex A, Graham Alison I AI, Trotter Eleanor W EW, Asif H M Shahzad HM, Sanguinetti Guido G, de Mattos Joost Teixeira JT, Poole Robert K RK, Green Jeffrey J"],"pubmed_abstract_synonyms":["biochemical pathways, Cytochrome, cytochrome b6, Metabolic Process, Activity, Effects, transferring electrons within CoQH2-cytochrome c reductase complex activity, Statistical Model, Processes, electron transporter, Statistical Models, Metabolic Concepts, E-948, bacterium E3, Gene, ubiquinol-cytochrome c oxidoreductase activity, 8O, complex III (mitochondrial electron transport) activity, protein, Metabolic Processes, protein-containing complex, Two-Parameter Model, Long Term, ubiquinol-cytochrome c-2 oxidoreductase activity, cytochrome b562, ubiquinol-cytochrome-c reductase activity, transferring electrons within cytochrome c oxidase complex activity, dioxygene, sensitive, Metabolism, Escherchia coli, oxigeno, cytochrome b566, Gene Products, Concepts, mitochondrial electron transport complex III, Enteroinvasive Escherichia coli, Enterococcus coli, Metabolism Concept, E948, protein aggregate, Phenomenon, Metabolism Phenomena, Effect, Models, sensitivity, cerebellar ataxia, anatomical systems, Escherichia/Shigella coli, Gene Expressions, Coenzyme Q, Longterm, catabolism, O, Oxygen-16, cytochrome, ARCA, General activity., E coli, Metabolic Concept, metabolic process resulting in cell growth, ubiquinone-cytochrome c oxidoreductase activity, Polynomial Model, Long-Term, Expressions, Binomial Models, E. coli, Eschericia coli, Enteroaggregative Escherichia coli, allergic reaction, Oxygen, arca, [OO], cytochrome c1, cytochrome a3/copper complex, cytochrome b/b6, ubiquinol:ferricytochrome-c oxidoreductase activity, biotransformation, Long-Term Effect, Expression, Model, Catabolism, phosphatase, Long-Term Effects, molecular oxygen, Alkalescens-Dispar Group, Polynomial, cytochrome f, Bacterium coli, Oxygen 16, degradation, Process, protein complex, metabolism resulting in cell growth, Proteins, Longterm Effect, soluble cytochrome b562, EAggEC, Binomial Model, Enteroaggregative E. coli, Fermentations, INSDC_feature:misc_RNA, cytochrome c, oxygen, cytochrome a, predicted, ubiquinone--cytochrome-c oxidoreductase activity, Concept, Metabolic Phenomena, Metabolism Concepts, native protein, Redox, Sauerstoff, Diffusely Adherent E. coli, Bacillus coli, Long Term Effects, Protein, Phenomena, Binomial, secretion, oxygene, regulator, metabolism, Two Parameter Models, OXYGEN MOLECULE, Two-Parameter, Metabolic Phenomenon, autosomal recessive, cytochrome bc1 complex, O2, Disauerstoff, dioxygen, Diffusely Adherent Escherichia coli, multicellular organism metabolic process, Probabilistic Models, Polynomial Models, Enteroinvasive E. coli, biodegradation, ubiquinol-cytochrome c1 oxidoreductase activity, Metabolic, phosphoric monoester hydrolase activity, ubiquinone-cytochrome c reductase activity, Longterm Effects, ubiquinol-cytochrome c2 reductase activity, Probabilistic Model, Protein Gene Products, Gene Proteins, Probabilistic, Bacterium coli commune, Two-Parameter Models, Aerobioses, Statistical, E 948, General activity, Oxidation Reduction, Dioxygen, Anabolism"],"description_synonyms":["F14P3.4, RNA polymerase II core promoter proximal region sequence-specific binding, Transcription, T-cell leukemia, Scientific Equipment, Factors, copper ion regulated core promoter proximal region sequence-specific binding., AGL4, F14P3_4, F10N7_150, Inferred, Infer, zinc ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, homeobox 1, Factor, SEPALLATA 2, metal ion regulated core promoter proximal region sequence-specific binding, metal ion regulated sequence-specific DNA binding RNA polymerase II transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity, Transcription Factor, Transcription factor, F10N7.150, Tool, transcription factor activity, zinc ion regulated core promoter proximal region sequence-specific DNA binding, Inference, RNA polymerase II proximal promoter sequence-specific DNA binding, copper ion regulated proximal promoter sequence-specific DNA binding, RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity, copper ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, AGAMOUS-like 4, RNA polymerase II transcription factor activity, Equipment, zinc ion regulated proximal promoter sequence-specific DNA binding, sequence-specific transcription regulatory region DNA binding RNA polymerase II transcription factor recruiting transcription factor activity, sequence-specific distal enhancer binding RNA polymerase II transcription factor activity, metal ion regulated sequence-specific DNA binding, metal ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, KNOTTED1-like homeobox gene 5, metal ion regulated proximal promoter sequence-specific DNA binding, TRANSCRIPTION FACTOR, RNA polymerase II distal enhancer sequence-specific binding"],"pubmed_title_synonyms":["cerebellar ataxia, O2, Disauerstoff, dioxygen, Oxygen 16, Activity, O, Escherichia coli K12, Oxygen-16, ARCA, E-948, 8O, INSDC_feature:misc_RNA, oxygen, arca, Oxygen, [OO], dioxygene, Sauerstoff, oxigeno, Dioxygen., oxygene, E948, E 948, General activity, OXYGEN MOLECULE, autosomal recessive, molecular oxygen"],"name_synonyms":["F14P3.4, RNA polymerase II core promoter proximal region sequence-specific binding, Transcription, T-cell leukemia, Scientific Equipment, Factors, copper ion regulated core promoter proximal region sequence-specific binding., AGL4, F14P3_4, F10N7_150, Inferred, Infer, zinc ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, homeobox 1, Factor, SEPALLATA 2, metal ion regulated core promoter proximal region sequence-specific binding, metal ion regulated sequence-specific DNA binding RNA polymerase II transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity, Transcription Factor, Transcription factor, F10N7.150, Tool, transcription factor activity, zinc ion regulated core promoter proximal region sequence-specific DNA binding, Inference, RNA polymerase II proximal promoter sequence-specific DNA binding, copper ion regulated proximal promoter sequence-specific DNA binding, RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity, copper ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, AGAMOUS-like 4, RNA polymerase II transcription factor activity, Equipment, zinc ion regulated proximal promoter sequence-specific DNA binding, sequence-specific transcription regulatory region DNA binding RNA polymerase II transcription factor recruiting transcription factor activity, sequence-specific distal enhancer binding RNA polymerase II transcription factor activity, metal ion regulated sequence-specific DNA binding, metal ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, KNOTTED1-like homeobox gene 5, metal ion regulated proximal promoter sequence-specific DNA binding, TRANSCRIPTION FACTOR, RNA polymerase II distal enhancer sequence-specific binding"],"additional_accession":[]},"is_claimable":false,"name":"TFInfer: a tool for probabilistic inference of transcription factor activities","description":"TFInfer: a tool for probabilistic inference of transcription factor activities","dates":{"created":"2013-01-14","publication":"2013-01-14","submission":"2013-01-14","last_modified":"2013-01-14"},"accession":"102","cross_references":{"pubmed":["20739311","22870390","21252224"]}}