ArticlePloS one2015
Using bioconductor package BiGGR for metabolic flux estimation based on gene expression changes in brain.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Evaluation of Metabolic and Synaptic Dysfunction Hypotheses of Alzheimer's Disease (AD): A Meta-Analysis of CSF Markers.Current Alzheimer research · 2018Pooled it
- Multi-omic profiling defines three distinct molecular subtypes of urothelial carcinoma with implications for precision therapy.Clinical and translational medicine · 2026Article
- Flux sampling and context-specific genome-scale metabolic models for biotechnological applications.Trends in biotechnology · 2026Review
- Biological and therapeutic implications of sex hormone-related gene clustering in testicular cancer.Basic and clinical andrology · 2025Article
- Metabolic function-based normalization improves transcriptome data-driven reduction of genome-scale metabolic models.NPJ systems biology and applications · 2023Article
- A chemokine network of T cell exhaustion and metabolic reprogramming in renal cell carcinoma.Frontiers in immunology · 2023Article
- A Standardized Brain Molecular Atlas: A Resource for Systems Modeling and Simulation.Frontiers in molecular neuroscience · 2021Article
- The metaRbolomics Toolbox in Bioconductor and beyond.Metabolites · 2019Review
- Integration of probabilistic regulatory networks into constraint-based models of metabolism with applications to Alzheimer's disease.BMC bioinformatics · 2019Article
- Recent Advances in the Systems Biology of Aging.Antioxidants & redox signaling · 2018Review
- Computational prediction of changes in brain metabolic fluxes during Parkinson's disease from mRNA expression.PloS one · 2018Article
- Integrating Extracellular Flux Measurements and Genome-Scale Modeling Reveals Differences between Brown and White Adipocytes.Cell reports · 2017Article
- Understanding the physiology of the ageing individual: computational modelling of changes in metabolism and endurance.Interface focus · 2016Review
- BiGG Models: A platform for integrating, standardizing and sharing genome-scale models.Nucleic acids research · 2016Article
- Forward Individualized Medicine from Personal Genomes to Interactomes.Frontiers in physiology · 2015Review
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Authors and funding
6 authors.
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Abstract
Predicting the distribution of metabolic fluxes in biochemical networks is of major interest in systems biology. Several databases provide metabolic reconstructions for different organisms. Software to analyze flux distributions exists, among others for the proprietary MATLAB environment. Given the large user community for the R computing environment, a simple implementation of flux analysis in R appears desirable and will facilitate easy interaction with computational tools to handle gene expression data. We extended the R software package BiGGR, an implementation of metabolic flux analysis in R. BiGGR makes use of public metabolic reconstruction databases, and contains the BiGG database and the reconstruction of human metabolism Recon2 as Systems Biology Markup Language (SBML) objects. Models can be assembled by querying the databases for pathways, genes or reactions of interest. Fluxes can then be estimated by maximization or minimization of an objective function using linear inverse modeling algorithms. Furthermore, BiGGR provides functionality to quantify the uncertainty in flux estimates by sampling the constrained multidimensional flux space. As a result, ensembles of possible flux configurations are constructed that agree with measured data within precision limits. BiGGR also features automatic visualization of selected parts of metabolic networks using hypergraphs, with hyperedge widths proportional to estimated flux values. BiGGR supports import and export of models encoded in SBML and is therefore interoperable with different modeling and analysis tools. As an application example, we calculated the flux distribution in healthy human brain using a model of central carbon metabolism. We introduce a new algorithm termed Least-squares with equalities and inequalities Flux Balance Analysis (Lsei-FBA) to predict flux changes from gene expression changes, for instance during disease. Our estimates of brain metabolic flux pattern with Lsei-FBA for Alzheimer's disease agree with independent measurements of cerebral metabolism in patients. This second version of BiGGR is available from Bioconductor.
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