Figure 3.

CHO Cells Undergo a Shift in Transcriptional and Metabolic Profile during Cell Culture

(A) Time course data for (i) genes that constitute top 10% variance across the samples, (ii) the intracellular metabolites, (iii) extracellular metabolites, and (iv) mAb glycoforms were correlated with all other samples, and the samples were clustered based on their pairwise Spearman correlation coefficients.

(B) Principal-component analysis of the transcriptomic, metabolomic, and glycan data. The first and second (top panel) or third (bottom panel) principal components together account for ∼60%–90% of the variance in the omics data and show temporal shift in the CHO transcriptional and metabolic profile from growth phase (day 0 to day 7) to production phase (day 7 to day 12).

(C) Time course data for process parameters were correlated with all other samples, and the samples were clustered based on their pairwise Spearman correlation coefficients showing that the parameters cluster separately for the two process conditions (HD and CD), regardless of the growth phase and production phase. Process variables included in the analysis are glucose, lactate, glutamate, pH, media feed, base feed, glucose feed, and ICP metals (fed differently in the two processes). As the units of each of the variables differ, the data were z-normalized for each variable before calculating the Spearman correlations.