title: A Systematic Approach to Time-series Metabolite Profiling and RNA-seq Analysis of Chinese Hamster Ovary Cell Culture.
abstract: Chinese hamster ovary (CHO) cells are the primary host used for biopharmaceutical protein production. The engineering of CHO cells to produce higher amounts of biopharmaceuticals has been highly dependent on empirical approaches, but recent high-throughput "omics" methods are changing the situation in a rational manner. Omics data analyses using gene expression or metabolite profiling make it possible to identify key genes and metabolites in antibody production. Systematic omics approaches using different types of time-series data are expected to further enhance understanding of cellular behaviours and molecular networks for rational design of CHO cells. This study developed a systematic method for obtaining and analysing time-dependent intracellular and extracellular metabolite profiles, RNA-seq data (enzymatic mRNA levels) and cell counts from CHO cell cultures to capture an overall view of the CHO central metabolic pathway (CMP). We then calculated correlation coefficients among all the profiles and visualised the whole CMP by heatmap analysis and metabolic pathway mapping, to classify genes and metabolites together. This approach provides an efficient platform to identify key genes and metabolites in CHO cell culture.
authors.affiliation: Graduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan.
authors.forename: Han-Hsiu
authors.initials: HH
authors.lastname: Hsu
authors.affiliation: Graduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Araki
authors.affiliation: Graduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Mochizuki
authors.affiliation: Graduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Hori
authors.affiliation: Graduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Murata
authors.affiliation: Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan.
authors.forename: Prihardi
authors.initials: P
authors.lastname: Kahar
authors.affiliation: Graduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Graduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Hasunuma
authors.affiliation: Graduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan.|Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kondo
mesh_terms: D000818:Animals; D016466:CHO Cells; D049109:Cell Proliferation; D019295:Computational Biology / Q000379:methods; D003412:Cricetulus; D005110:Extracellular Space / Q000378:metabolism; D020869:Gene Expression Profiling; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D005947:Glucose / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D017423:Sequence Analysis, RNA; D059467:Transcriptome
chemical_list: D019344:Lactic Acid; D005947:Glucose