Deciphering the determinants of recombinant protein yield across the human secretome
Masson, H. O.; Kuo, C.-C.; Malm, M.; Lundqvist, M.; Sivertsson, A.; Berling, A.; Tegel, H.; Hober, S.; Uhlen, M.; Grassi, L.; Hatton, D.; Rockberg, J.; Lewis, N. E.
Show abstract
Mammalian cells are critical hosts for the production of most therapeutic proteins and many proteins for biomedical research. While cell line engineering and bioprocess optimization have yielded high protein titers of some recombinant proteins, many proteins remain difficult to express. Here, we decipher the factors influencing yields in Chinese hamster ovary (CHO) cells as they produce 2165 different proteins from the human secretome. We demonstrate that variation within our panel of proteins cannot be explained by transgene mRNA abundance. Analyzing the expression of the 2165 human proteins with machine learning, we find that protein features account for only 15% of the variability in recombinant protein yield. Meanwhile, transcriptomic signatures account for 75% of the variability across 95 representative samples. In particular, we observe divergent signatures regarding ER stress and metabolism among the panel of cultures expressing different recombinant proteins. Thus, our study unravels the factors underlying the variation on recombinant protein production in CHO and highlights transcriptomics signatures that could guide the rational design of CHO cell systems tailored to specific proteins.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Multi-omic profiling of pathogen-stimulated primary immune cells 92%
- Signal transduction pathways controlling Ins2 gene activity and β cell state transitions 92%
- Comparing the impact of sample multiplexing approaches for single-cell RNA-sequencing on downstream analysis using cerebellar organoids 91%
Similar papers in this journal
- Harnessing secretory pathway differences between HEK293 and CHO to rescue production of difficult to express proteins 94%
- A metabolic CRISPR-Cas9 screen in Chinese hamster ovary cells identifies glutamine-sensitive genes 93%
- Systematic evaluation of parameters for genome-scale metabolic models of cultured mammalian cells 92%
Similar papers in this journal
- Regulation of protein secretion through chemical regulation of endoplasmic reticulum retention signal cleavage 94%
- Degradation Bottlenecks and Resource Competition in Transiently and Stably Engineered Mammalian Cells 93%
- A dual-reporter system for investigating and optimizing protein translation and folding in E. coli 93%
Similar papers in this journal
- Principles for Systematic Optimization of an Orthogonal Translation System with Enhanced Biological Tolerance 93%
- Metabolic mapping of the human solute carrier superfamily 92%
- hu.MAP 2.0: Integration of over 15,000 proteomic experiments builds a global compendium of human multiprotein assemblies 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.