ArticleBMC systems biology2011
Integration of lipidomics and transcriptomics data towards a systems biology model of sphingolipid metabolism.
Article in BMC systems biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Characterizing human mesenchymal stromal cells' immune-modulatory potency using targeted lipidomic profiling of sphingolipids.Cytotherapy · 2022Article
- Dissecting the regulatory roles of ORM proteins in the sphingolipid pathway of plants.PLoS computational biology · 2021Article
- Modulation of DNA Damage Response by Sphingolipid Signaling: An Interplay that Shapes Cell Fate.International journal of molecular sciences · 2020Review
- Lipidomics from sample preparation to data analysis: a primer.Analytical and bioanalytical chemistry · 2020Review
- Acid sphingomyelinase deficiency protects mitochondria and improves function recovery after brain injury.Journal of lipid research · 2019Article
- Quantitative Systems Pharmacology Modeling of Acid Sphingomyelinase Deficiency and the Enzyme Replacement Therapy Olipudase Alfa Is an Innovative Tool for Linking Pathophysiology and Pharmacology.CPT: pharmacometrics & systems pharmacology · 2018Article
- Mechanistic interplay between ceramide and insulin resistance.Scientific reports · 2017Article
- Transcriptomics-driven lipidomics (TDL) identifies the microbiome-regulated targets of ileal lipid metabolism.NPJ systems biology and applications · 2017Article
- Computational Modeling of Competitive Metabolism between ω3- and ω6-Polyunsaturated Fatty Acids in Inflammatory Macrophages.The journal of physical chemistry. B · 2016Article
- Computational modeling of sphingolipid metabolism.BMC systems biology · 2015Article
- Computationally Modeling Lipid Metabolism and Aging: A Mini-review.Computational and structural biotechnology journal · 2015Review
- Article
- Human trabecular meshwork sphingolipid and ceramide profiles and potential latent fungal commensalism.Investigative ophthalmology & visual science · 2014Article
- Re-configuration of sphingolipid metabolism by oncogenic transformation.Biomolecules · 2014Review
- Modeling of eicosanoid fluxes reveals functional coupling between cyclooxygenases and terminal synthases.Biophysical journal · 2014Article
- Mapping condition-dependent regulation of lipid metabolism in Saccharomyces cerevisiae.G3 (Bethesda, Md.) · 2013Article
- Reverse engineering biomolecular systems using -omic data: challenges, progress and opportunities.Briefings in bioinformatics · 2012Article
- A genome-scale metabolic model of the lipid-accumulating yeast Yarrowia lipolytica.BMC systems biology · 2012Article
- Nuclear sphingolipid metabolism.Annual review of physiology · 2012Review
- Sphingolipid and glycosphingolipid metabolic pathways in the era of sphingolipidomics.Chemical reviews · 2011Review
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Authors and funding
5 authors.
Funding
Abstract
backgroundSphingolipids play important roles in cell structure and function as well as in the pathophysiology of many diseases. Many of the intermediates of sphingolipid biosynthesis are highly bioactive and sometimes have antagonistic activities, for example, ceramide promotes apoptosis whereas sphingosine-1-phosphate can inhibit apoptosis and induce cell growth; therefore, quantification of the metabolites and modeling of the sphingolipid network is imperative for an understanding of sphingolipid biology.
resultsIn this direction, the LIPID MAPS Consortium is developing methods to quantitate the sphingolipid metabolites in mammalian cells and is investigating their application to studies of the activation of the RAW264.7 macrophage cell by a chemically defined endotoxin, Kdo2-Lipid A. Herein, we describe a model for the C16-branch of sphingolipid metabolism (i.e., for ceramides with palmitate as the N-acyl-linked fatty acid, which is selected because it is a major subspecies for all categories of complex sphingolipids in RAW264.7 cells) integrating lipidomics and transcriptomics data and using a two-step matrix-based approach to estimate the rate constants from experimental data. The rate constants obtained from the first step are further refined using generalized constrained nonlinear optimization. The resulting model fits the experimental data for all species. The robustness of the model is validated through parametric sensitivity analysis.
conclusionsA quantitative model of the sphigolipid pathway is developed by integrating metabolomics and transcriptomics data with legacy knowledge. The model could be used to design experimental studies of how genetic and pharmacological perturbations alter the flux through this important lipid biosynthetic pathway.
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