期刊
CELL SYSTEMS
卷 1, 期 4, 页码 270-282出版社
CELL PRESS
DOI: 10.1016/j.cels.2015.09.008
关键词
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资金
- EMBO fellowship
- SystemsX.ch IPhD fellowship
Hundreds of molecular-level changes within central metabolism allow a cell to adapt to the changing environment. A primary challenge in cell physiology is to identify which of these molecular-level changes are active regulatory events. Here, we introduce pseudo-transition analysis, an approach that uses multiple steady-state observations of C-13-resolved fluxes, metabolites, and transcripts to infer which regulatory events drive metabolic adaptations following environmental transitions. Pseudo-transition analysis recapitulates known biology and identifies an unexpectedly sparse, transition-dependent regulatory landscape: typically a handful of regulatory events drive adaptation between carbon sources, with transcription mainly regulating TCA cycle flux and reactants regulating EMP pathway flux. We verify these observations using time-resolved measurements of the diauxic shift, demonstrating that some dynamic transitions can be approximated as monotonic shifts between steady-state extremes. Overall, we show that pseudo-transition analysis can explore the vast regulatory landscape of dynamic transitions using relatively few steady-state data, thereby guiding time-consuming, hypothesisdriven molecular validations.
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