title: Network reconstruction of the mouse secretory pathway applied on CHO cell transcriptome data.
abstract: Protein secretion is one of the most important processes in eukaryotes. It is based on a highly complex machinery involving numerous proteins in several cellular compartments. The elucidation of the cell biology of the secretory machinery is of great importance, as it drives protein expression for biopharmaceutical industry, a 140 billion USD global market. However, the complexity of secretory process is difficult to describe using a simple reductionist approach, and therefore a promising avenue is to employ the tools of systems biology.
  
  
  
  On the basis of manual curation of the literature on the yeast, human, and mouse secretory pathway, we have compiled a comprehensive catalogue of characterized proteins with functional annotation and their interconnectivity. Thus we have established the most elaborate reconstruction (RECON) of the functional secretion pathway network to date, counting 801 different components in mouse. By employing our mouse RECON to the CHO-K1 genome in a comparative genomic approach, we could reconstruct the protein secretory pathway of CHO cells counting 764 CHO components. This RECON furthermore facilitated the development of three alternative methods to study protein secretion through graphical visualizations of omics data. We have demonstrated the use of these methods to identify potential new and known targets for engineering improved growth and IgG production, as well as the general observation that CHO cells seem to have less strict transcriptional regulation of protein secretion than healthy mouse cells.
  
  
  
  The RECON of the secretory pathway represents a strong tool for interpretation of data related to protein secretion as illustrated with transcriptomic data of Chinese Hamster Ovary (CHO) cells, the main platform for mammalian protein production.
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads 223, DK-2800, Kgs. Lyngby, Denmark.
authors.forename: Anne Mathilde
authors.initials: AM
authors.lastname: Lund
authors.affiliation: Recombinant Expression Technologies, Global Research Unit, Novo Nordisk A/S, Novo Nordisk Park, DK-2760, Måløv, Denmark.
authors.forename: Christian Schrøder
authors.initials: CS
authors.lastname: Kaas
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads 223, DK-2800, Kgs. Lyngby, Denmark.
authors.forename: Julian
authors.initials: J
authors.lastname: Brandl
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet 220, DK-2800, Kgs. Lyngby, Denmark.
authors.forename: Lasse Ebdrup
authors.initials: LE
authors.lastname: Pedersen
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet 220, DK-2800, Kgs. Lyngby, Denmark.
authors.forename: Helene Faustrup
authors.initials: HF
authors.lastname: Kildegaard
authors.affiliation: Faculty of Health and Medical Sciences, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3B, DK-2200, København N, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Kristensen
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads 223, DK-2800, Kgs. Lyngby, Denmark. mr@bio.dtu.dk.
authors.forename: Mikael Rørdam
authors.identifier: 0000-0003-4794-6808
authors.initials: MR
authors.lastname: Andersen
mesh_terms: D000818:Animals; D016466:CHO Cells; D019295:Computational Biology / Q000379:methods*; D006224:Cricetinae; D003412:Cricetulus; D020869:Gene Expression Profiling; D063990:Gene Ontology; D051379:Mice; D055571:Secretory Pathway / Q000235:genetics*
keywords: Chinese hamster ovary cells; Pathway reconstruction; Protein secretion; RNA-Seq; Secretion pathway