Reference - Detail
| RRC ID | 53674 |
|---|---|
| Author | Gerosa L, Haverkorn van Rijsewijk BR, Christodoulou D, Kochanowski K, Schmidt TS, Noor E, Sauer U. |
| Title | Pseudo-transition Analysis Identifies the Key Regulators of Dynamic Metabolic Adaptations from Steady-State Data. |
| Journal | Cell Syst |
| Abstract |
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 (13)C-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, hypothesis-driven molecular validations. |
| Volume | 1(4) |
| Pages | 270-82 |
| Published | 2015-10-28 |
| DOI | 10.1016/j.cels.2015.09.008 |
| PII | S2405-4712(15)00146-5 |
| PMID | 27136056 |
| IF | 8.673 |
| Times Cited | 49 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 9 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Prokaryotes E. coli | |