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Sökning: WFRF:(Holman Stephen W.)

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1.
  • El-Semman, Ibrahim, 1977, et al. (författare)
  • Whole-cell modeling in yeast predicts compartment-specific proteome constraints that drive metabolic strategies
  • 2022
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • When conditions change, unicellular organisms rewire their metabolism to sustain cell maintenance and cellular growth. Such rewiring may be understood as resource re-allocation under cellular constraints. Eukaryal cells contain metabolically active organelles such as mitochondria, competing for cytosolic space and resources, and the nature of the relevant cellular constraints remain to be determined for such cells. Here, we present a comprehensive metabolic model of the yeast cell, based on its full metabolic reaction network extended with protein synthesis and degradation reactions. The model predicts metabolic fluxes and corresponding protein expression by constraining compartment-specific protein pools and maximising growth rate. Comparing model predictions with quantitative experimental data suggests that under glucose limitation, a mitochondrial constraint limits growth at the onset of ethanol formation-known as the Crabtree effect. Under sugar excess, however, a constraint on total cytosolic volume dictates overflow metabolism. Our comprehensive model thus identifies condition-dependent and compartment-specific constraints that can explain metabolic strategies and protein expression profiles from growth rate optimisation, providing a framework to understand metabolic adaptation in eukaryal cells.
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2.
  • Qi, Da, et al. (författare)
  • Representation of selected-reaction monitoring data in the mzQuantML data standard
  • 2015
  • Ingår i: Proteomics. - : Wiley. - 1615-9861 .- 1615-9853. ; 15:15, s. 2592-2596
  • Tidskriftsartikel (refereegranskat)abstract
    • The mzQuantML data standard was designed to capture the output of quantitative software in proteomics, to support submissions to public repositories, development of visualization software and pipeline/modular approaches. The standard is designed around a common core that can be extended to support particular types of technique through the release of semantic rules that are checked by validation software. The first release of mzQuantML supported four quantitative proteomics techniques via four sets of semantic rules: (i) intensity-based (MS1) label free, (ii) MS1 label-based (such as SILAC or N-15), (iii) MS2 tag-based (iTRAQ or tandem mass tags), and (iv) spectral counting. We present an update to mzQuantML for supporting SRM techniques. The update includes representing the quantitative measurements, and associated meta-data, for SRM transitions, the mechanism for inferring peptide-level or protein-level quantitative values, and support for both label-based or label-free SRM protocols, through the creation of semantic rules and controlled vocabulary terms. We have updated the specification document for mzQuantML (version 1.0.1) and the mzQuantML validator to ensure that consistent files are produced by different exporters. We also report the capabilities for production of mzQuantML files from popular SRM software packages, such as Skyline and Anubis.
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