Network reconstruction of the mouse secretory pathway applied on CHO cell transcriptome data

• Published in: BMC systems biology 2017-03, Vol.11 (1), p.37-37, Article 37
• Main Authors: Lund, Anne Mathilde, Kaas, Christian Schrøder, Brandl, Julian, Pedersen, Lasse Ebdrup, Kildegaard, Helene Faustrup, Kristensen, Claus, Andersen, Mikael Rørdam
• Format: Article
• Language: English
• Subjects: Amino acids; Animal models; Animals; Benchmarks; Biodegradation; Bioinformatics; Biological activity; Biological effects; Biology; Biotechnology; Cancer; Carbon dioxide; Cell culture; Cell lines; CHO Cells; Chromatin remodeling; Cloning; Compartments; Computational Biology - methods; Computer architecture; Computer programs; Cricetinae; Cricetulus; Degradation; Deoxyribonucleic acid; Differentiation; DNA; Documents; Endoplasmic reticulum; Environment models; Environmental changes; Eukaryotes; Fungi; Gene expression; Gene Expression Profiling; Gene mapping; Gene Ontology; Gene regulation; Genomes; Genomics; Heterogeneity; Homology; Immunoglobulin G; Industrial production; Malfunctions; Mammals; Materials handling; Metabolism; Metabolites; Mice; Movement disorders; Neurodegenerative diseases; Nucleic acids; Nutrient availability; Parkinson's disease; Proteins; Quality; Quality control; Rodents; Secretory Pathway - genetics; Signal transduction; Sodium; Stress; Stresses; Traffic; Transcription; Viability
• ISSN: 1752-0509; 1752-0509
• DOI: 10.1186/s12918-017-0414-4

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.