LAPSE:2020.0475
Published Article

LAPSE:2020.0475
Integration of Time-Series Transcriptomic Data with Genome-Scale CHO Metabolic Models for mAb Engineering
May 22, 2020
Abstract
Chinese hamster ovary (CHO) cells are the most commonly used cell lines in biopharmaceutical manufacturing. Genome-scale metabolic models have become a valuable tool to study cellular metabolism. Despite the presence of reference global genome-scale CHO model, context-specific metabolic models may still be required for specific cell lines (for example, CHO-K1, CHO-S, and CHO-DG44), and for specific process conditions. Many integration algorithms have been available to reconstruct specific genome-scale models. These methods are mainly based on integrating omics data (i.e., transcriptomics, proteomics, and metabolomics) into reference genome-scale models. In the present study, we aimed to investigate the impact of time points of transcriptomics integration on the genome-scale CHO model by assessing the prediction of growth rates with each reconstructed model. We also evaluated the feasibility of applying extracted models to different cell lines (generated from the same parental cell line). Our findings illustrate that gene expression at various stages of culture slightly impacts the reconstructed models. However, the prediction capability is robust enough on cell growth prediction not only across different growth phases but also in expansion to other cell lines.
Chinese hamster ovary (CHO) cells are the most commonly used cell lines in biopharmaceutical manufacturing. Genome-scale metabolic models have become a valuable tool to study cellular metabolism. Despite the presence of reference global genome-scale CHO model, context-specific metabolic models may still be required for specific cell lines (for example, CHO-K1, CHO-S, and CHO-DG44), and for specific process conditions. Many integration algorithms have been available to reconstruct specific genome-scale models. These methods are mainly based on integrating omics data (i.e., transcriptomics, proteomics, and metabolomics) into reference genome-scale models. In the present study, we aimed to investigate the impact of time points of transcriptomics integration on the genome-scale CHO model by assessing the prediction of growth rates with each reconstructed model. We also evaluated the feasibility of applying extracted models to different cell lines (generated from the same parental cell line). Our findings illustrate that gene expression at various stages of culture slightly impacts the reconstructed models. However, the prediction capability is robust enough on cell growth prediction not only across different growth phases but also in expansion to other cell lines.
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Keywords
CHO cell, genome-scale metabolic model, omics data integration, time-series transcriptomics
Subject
Suggested Citation
Huang Z, Yoon S. Integration of Time-Series Transcriptomic Data with Genome-Scale CHO Metabolic Models for mAb Engineering. (2020). LAPSE:2020.0475
Author Affiliations
Huang Z: Chemical Engineering, University of Massachusetts Lowell, Lowell, MA 01850, USA
Yoon S: Chemical Engineering, University of Massachusetts Lowell, Lowell, MA 01850, USA
Yoon S: Chemical Engineering, University of Massachusetts Lowell, Lowell, MA 01850, USA
Journal Name
Processes
Volume
8
Issue
3
Article Number
E331
Year
2020
Publication Date
2020-03-11
ISSN
2227-9717
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Original Submission
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PII: pr8030331, Publication Type: Journal Article
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LAPSE:2020.0475
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https://doi.org/10.3390/pr8030331
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[v1] (Original Submission)
May 22, 2020
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Record Owner
Calvin Tsay
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