Model-based assessment of mammalian cell metabolic functionalities using omics data.; ; et al in Cell reports methods (2021), 1(3), Omics experiments are ubiquitous in biological studies, leading to a deluge of data. However, it is still challenging to connect changes in these data to changes in cell functions because of complex ... [more ▼] Omics experiments are ubiquitous in biological studies, leading to a deluge of data. However, it is still challenging to connect changes in these data to changes in cell functions because of complex interdependencies between genes, proteins, and metabolites. Here, we present a framework allowing researchers to infer how metabolic functions change on the basis of omics data. To enable this, we curated and standardized lists of metabolic tasks that mammalian cells can accomplish. Genome-scale metabolic networks were used to define gene sets associated with each metabolic task. We further developed a framework to overlay omics data on these sets and predict pathway usage for each metabolic task. We demonstrated how this approach can be used to quantify metabolic functions of diverse biological samples from the single cell to whole tissues and organs by using multiple transcriptomic datasets. To facilitate its adoption, we integrated the approach into GenePattern (www.genepattern.org-CellFie). [less ▲] Detailed reference viewed: 81 (1 UL) Creation and analysis of biochemical constraint-based models using the COBRA Toolbox v.3.0.Heirendt, Laurent ; ; Pfau, Thomas et alin Nature protocols (2019), 14(3), 639-702 Constraint-based reconstruction and analysis (COBRA) provides a molecular mechanistic framework for integrative analysis of experimental molecular systems biology data and quantitative prediction of ... [more ▼] Constraint-based reconstruction and analysis (COBRA) provides a molecular mechanistic framework for integrative analysis of experimental molecular systems biology data and quantitative prediction of physicochemically and biochemically feasible phenotypic states. The COBRA Toolbox is a comprehensive desktop software suite of interoperable COBRA methods. It has found widespread application in biology, biomedicine, and biotechnology because its functions can be flexibly combined to implement tailored COBRA protocols for any biochemical network. This protocol is an update to the COBRA Toolbox v.1.0 and v.2.0. Version 3.0 includes new methods for quality-controlled reconstruction, modeling, topological analysis, strain and experimental design, and network visualization, as well as network integration of chemoinformatic, metabolomic, transcriptomic, proteomic, and thermochemical data. New multi-lingual code integration also enables an expansion in COBRA application scope via high-precision, high-performance, and nonlinear numerical optimization solvers for multi-scale, multi-cellular, and reaction kinetic modeling, respectively. This protocol provides an overview of all these new features and can be adapted to generate and analyze constraint-based models in a wide variety of scenarios. The COBRA Toolbox v.3.0 provides an unparalleled depth of COBRA methods. [less ▲] Detailed reference viewed: 383 (47 UL) |
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