SEEK ID: https://fairdomhub.org/studies/1138
Mitochondrial fatty acid oxidation in human liver
Projects: PoLiMeR - Polymers in the Liver: Metabolism and Regulation
Study position: 2
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Created: 23rd Feb 2023 at 14:58
Last updated: 7th Mar 2023 at 14:31
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Projects: SilicoTryp, Multiscale modelling of state transitions in the host-microbiome-brain network, MESI-STRAT, PoLiMeR - Polymers in the Liver: Metabolism and Regulation
Institutions: University of Groningen
https://orcid.org/0000-0001-6274-3633I am a Professor in Medical Systems Biology and the University Medical Centre Groningen. The research in my lab is focused on complex regulation of mammalian lipid and carbohydrate metabolism, eventually aiming at network-based therapies. We combine dynamic computer simulations with quantitative metabolomics, 13C fluxomics, proteomics and transcriptome analysis, and in depth biochemical analysis. This allows to predict and understand ‘emergent’ properties, those properties that are counterintuitive ...
Projects: PoLiMeR - Polymers in the Liver: Metabolism and Regulation
Institutions: University of Leiden
Projects: PoLiMeR - Polymers in the Liver: Metabolism and Regulation
Institutions: University Medical Centre Groningen
PoLiMeR is funded through the EU Marie Skłodowska-Curie Innovative Training Network (ITN), which drives scientific excellence and innovation. ITNs bring together universities, research institutes, industry and clinical partners from across the world to train researchers to doctorate level.
Metabolic diseases are a burden on the European population and health care system. It is increasingly recognised that individual differences with respect to history, lifestyle, and genetic make-up affect disease ...
Programme: This Project is not associated with a Programme
Public web page: http://polimer-itn.eu/
Organisms: Homo sapiens, Mus musculus, Rattus norvegicus
Submitter: Christoff Odendaal
Studies: Model analysis, Model construction, Model validation
Assays: ACAD activity partitioning, Comparing acyl-CoA dehydrogenase deficiencies, HepG2 oxygen consumption, Kinetics Minireviews, MCADD patient personalised modelling, MCADD rescue titration, Metabolic control analysis, Models, Predicting urinary acylcarnitines under metabolic decompensation., Whole-body ketogenic flux
Snapshots: Snapshot 1
Prediction of patient urinary acylcarnitine under metabolic decompensation. Generates Fig. 3, Table 1, and Table S2 in the associated publication.
Download and unzip "Model_notebooks.rar" and run "7, Fig3+4+S1+S3-ACADDs-[needs-(1)]-20221109.nb" after running "1, generate-model-20221109.nb"
Submitter: Christoff Odendaal
Biological problem addressed: Model Analysis Type
Investigation: Mitochondrial fatty acid oxidation in human liver
Study: Model analysis
Organisms: No organisms
Models: Model notebooks, odendaal1
SOPs: No SOPs
Data files: No Data files
Snapshots: No snapshots
Based on odendaal1, a control model is made and compared to model deficient for short-chain acyl-CoA dehydrogenase (SCADD, 0%), medium-chain acyl-CoA dehydrogenase (MCADD, 0%), and very long-chain acyl-CoA dehydrogenase (VLCADD, 10%). With and withou metabolite partitioning, and with a fixed mitohondrial free CoASH. Generates Figures 3, 4, S1, S2, and S3 in the related paper.
Download "Model_notebooks.rar", unzip, and run: "7, Fig3+4+S1+S3-ACADDs-[needs-(1)]-20221109.nb" and "14, ...
Submitter: Christoff Odendaal
Biological problem addressed: Model Analysis Type
Investigation: Mitochondrial fatty acid oxidation in human liver
Study: Model analysis
Organisms: No organisms
Models: Model notebooks, odendaal1
SOPs: No SOPs
Data files: No Data files
Snapshots: No snapshots
Calculation of control and response coefficients. Generates Fig. 5, Fig. S4, and Table S2 in the associated publication.
Download "Model_notebooks.rar", unzip, and run: "8, Fig5-control-coefficients-[needs-(1)]-20221109.nb", "9, TableS2-response-coefficients-[needs-(1)]-20230302.nb", and "15, FigS4-control-coefficients-low-AcetylCoA-[needs-(1)]-20221109.nb" after running "1, generate-model-20221109.nb"
Submitter: Christoff Odendaal
Biological problem addressed: Model Analysis Type
Investigation: Mitochondrial fatty acid oxidation in human liver
Study: Model analysis
Organisms: No organisms
Models: Model notebooks, odendaal1
SOPs: No SOPs
Data files: No Data files
Snapshots: No snapshots
Incrementally increase the activity of some target rescue enzymes from 20% of default expression to 200% of default expression in a control and MCADD model to see if flux and CoASH concentration are rescued. Generates Fig. 6, S5, and S6.
Download "Model_notebooks.rar", unzip, and run "11, Fig6+S5-rescues-[needs-(1-and-10)]-20221109.nb", "10, Fig6B-inset-rescues-(low-acetylCoA)-[needs-(1)]-20221109.nb", and "16, FigS6-rescues-20221109-fixed-[needs-(1)]-CoASH.nb" after running "1, generate-model-20221109.nb" ...
Submitter: Christoff Odendaal
Biological problem addressed: Model Analysis Type
Investigation: Mitochondrial fatty acid oxidation in human liver
Study: Model analysis
Organisms: No organisms
Models: Model notebooks, odendaal1
SOPs: No SOPs
Data files: No Data files
Snapshots: No snapshots
Creation of personalised models of control, symptomatic MCADD, asymptomatic MCADD, and early diagnosis MCADD individuals using fibroblast proteomics to adjust model Vmaxes. Generates Fig. 7 and S7.
Download and unzip "Model_notebooks.rar" and run "13, Fig7-personalised-models-[needs-(1-and-12)]-20221109.nb" after running "1, generate-model-20221109.nb" and "12, Fig7-S7-preprocessing-[needs-(1)-]-20221109.nb".
Submitter: Christoff Odendaal
Biological problem addressed: Model Analysis Type
Investigation: Mitochondrial fatty acid oxidation in human liver
Study: Model analysis
Organisms: No organisms
Models: Model notebooks, odendaal1
SOPs: No SOPs
Data files: Fibroblasts proteomics
Snapshots: No snapshots
Proteomics from MCADD and control individuals' fibroblasts.
Creators: Christoff Odendaal, Barbara Bakker, Emmalie Jager, Terry G.J. Derks, Karin Wolters; Anne-Claire Martines
Submitter: Christoff Odendaal
Investigations: Mitochondrial fatty acid oxidation in human liver
Studies: Model analysis
Human mitochondrial fatty acid oxidation of saturated, even chain acyl-Coas beginning at C16. See Model description for detail.
Creators: Christoff Odendaal, Emmalie Jager, Barbara Bakker, Terry G.J. Derks
Submitter: Christoff Odendaal
Model type: Ordinary differential equations (ODE)
Model format: SBML
Environment: JWS Online
Organism: Not specified
Investigations: Mitochondrial fatty acid oxidation in human liver
Studies: Model analysis, Model construction, Model validation
Assays: Comparing acyl-CoA dehydrogenase deficiencies, MCADD patient personalised modelling, MCADD rescue titration, Metabolic control analysis, Models, Predicting urinary acylcarnitines under metabol..., Whole-body ketogenic flux
Unzip model notebooks and keep in the same folder. Notebook names state which notebooks need to be run before them in order for them to word, e.g. "[needs-(1)]" indicates that the notebook numbered 1 must be run and its exported output generated before the given notebook can work. This has to do with the model being generated in only one notebook to avoid duplication.
Creators: Christoff Odendaal, Barbara Bakker, Emmalie Jager, Terry G.J. Derks
Submitter: Christoff Odendaal
Model type: Ordinary differential equations (ODE)
Model format: Mathematica
Environment: Mathematica
Organism: Homo sapiens
Investigations: Mitochondrial fatty acid oxidation in human liver
Studies: Model analysis, Model construction, Model validation
Assays: ACAD activity partitioning, Comparing acyl-CoA dehydrogenase deficiencies, HepG2 oxygen consumption, MCADD patient personalised modelling, MCADD rescue titration, Metabolic control analysis, Models, Predicting urinary acylcarnitines under metabol..., Whole-body ketogenic flux