Distinct metabolic network structures and pathway activities revealed by 327 contextualized modeling of Zero Lactate CHO cells: (A) Schematic representation of the 328 context-specific genome-scale metabolic model reconstruction pipeline using iCHO3K. 329 This process yielded 24 models representing wild-type (WT) and Zero Lactate (ZeLa) 330

Contexts in source publication

Context 1

... we constrained each model with 303 experimentally-determined uptake and secretion rates and used the RMF mCADRE 304 toolbox 44 for model reduction (see Materials and Methods). Finally, we compared the 305 network topology and functional capabilities of the generated models ( Figure 3A). This 306 pipeline resulted in 27 context-specific models, comprising 9 models from CHO-S (WT) 307 was not certified by peer review) is the author/funder. ...

Context 2

... Additionally, some WT_P6 (day 6) models clustered with ZeLa_P8 (day 8) 319 models, which correlates with experimental data indicating that WT cell lines reach the 320 end of their exponential growth phase at day 6, while ZeLa cell lines do so at day 8 321 (Supplementary Figure 3A). This result highlights iCHO3K's ability to reflect metabolic 322 shifts corresponding to different time points and conditions in culture, and underscores 323 the utility of integrating RNA-Seq and spent media data into iCHO3K to account for the 324 topological and functional differences of metabolism, which is unclear in basic 325 transcriptomic data. ...

Context 3

... To simulate growth in the context-specific models generated, we employed 356 parsimonious flux balance analysis (pFBA) 46 Using the detailed enzyme annotation in iCHO3K, we employed ecFBA to explore 373 the entire space of feasible metabolic flux distributions between the CHO-ZeLa and CHO-374 S cell lines under the given experimental constraints (see Materials and Methods), 375 providing distributions for the fluxes through each reaction. We focused our analysis on 376 models corresponding to day 4, when both cell lines are in exponential growth 377 Figure 3A), to generate distributions for the fluxes through each 378 ...

Context 4

... we constrained each model with 303 experimentally-determined uptake and secretion rates and used the RMF mCADRE 304 toolbox 44 for model reduction (see Materials and Methods). Finally, we compared the 305 network topology and functional capabilities of the generated models ( Figure 3A). This 306 pipeline resulted in 27 context-specific models, comprising 9 models from CHO-S (WT) 307 was not certified by peer review) is the author/funder. ...

Context 5

... Additionally, some WT_P6 (day 6) models clustered with ZeLa_P8 (day 8) 319 models, which correlates with experimental data indicating that WT cell lines reach the 320 end of their exponential growth phase at day 6, while ZeLa cell lines do so at day 8 321 (Supplementary Figure 3A). This result highlights iCHO3K's ability to reflect metabolic 322 shifts corresponding to different time points and conditions in culture, and underscores 323 the utility of integrating RNA-Seq and spent media data into iCHO3K to account for the 324 topological and functional differences of metabolism, which is unclear in basic 325 transcriptomic data. ...

Context 6

... To simulate growth in the context-specific models generated, we employed 356 parsimonious flux balance analysis (pFBA) 46 Using the detailed enzyme annotation in iCHO3K, we employed ecFBA to explore 373 the entire space of feasible metabolic flux distributions between the CHO-ZeLa and CHO-374 S cell lines under the given experimental constraints (see Materials and Methods), 375 providing distributions for the fluxes through each reaction. We focused our analysis on 376 models corresponding to day 4, when both cell lines are in exponential growth 377 Figure 3A), to generate distributions for the fluxes through each 378 ...