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2012 | OriginalPaper | Buchkapitel

Advancing Biopharmaceutical Process Development by System-Level Data Analysis and Integration of Omics Data

verfasst von : Jochen Schaub, Christoph Clemens, Hitto Kaufmann, Torsten W. Schulz

Erschienen in: Genomics and Systems Biology of Mammalian Cell Culture

Verlag: Springer Berlin Heidelberg

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Abstract

Development of efficient bioprocesses is essential for cost-effective manufacturing of recombinant therapeutic proteins. To achieve further process improvement and process rationalization comprehensive data analysis of both process data and phenotypic cell-level data is essential.

Here, we present a framework for advanced bioprocess data analysis consisting of multivariate data analysis (MVDA), metabolic flux analysis (MFA), and pathway analysis for mapping of large-scale gene expression data sets. This data analysis platform was applied in a process development project with an IgG-producing Chinese hamster ovary (CHO) cell line in which the maximal product titer could be increased from about 5 to 8 g/L.

Principal component analysis (PCA), k-means clustering, and partial least-squares (PLS) models were applied to analyze the macroscopic bioprocess data. MFA and gene expression analysis revealed intracellular information on the characteristics of high-performance cell cultivations. By MVDA, for example, correlations between several essential amino acids and the product concentration were observed. Also, a grouping into rather cell specific productivity-driven and process control-driven processes could be unraveled. By MFA, phenotypic characteristics in glycolysis, glutaminolysis, pentose phosphate pathway, citrate cycle, coupling of amino acid metabolism to citrate cycle, and in the energy yield could be identified. By gene expression analysis 247 deregulated metabolic genes were identified which are involved, inter alia, in amino acid metabolism, transport, and protein synthesis.

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Vorheriges Kapitel Metabolic Flux Analysis in Systems Biology of Mammalian Cells

Nächstes Kapitel Protein Glycosylation and Its Impact on Biotechnology

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Titel: Advancing Biopharmaceutical Process Development by System-Level Data Analysis and Integration of Omics Data
verfasst von: Jochen Schaub
Christoph Clemens
Hitto Kaufmann
Torsten W. Schulz
Verlag: Springer Berlin Heidelberg
Buch: Genomics and Systems Biology of Mammalian Cell Culture
Print ISBN: 978-3-642-28349-9

Electronic ISBN: 978-3-642-28350-5

Copyright-Jahr: 2012
DOI: https://doi.org/10.1007/10_2010_98

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