Fantastic genes and where to find them expressed in CHO

The transcriptome of Chinese hamster ovary (CHO) cells plays a crucial role in determining cellular characteristics that are essential for biopharmaceutical applications. RNA-sequencing has been extensively used to profile gene expression patterns, aiming to gain a better understanding of intracellular behavior and mechanisms. Individual datasets, however, do not provide a comprehensive overview and characterization of the CHO cell's transcriptome, such that the fundamental structure of the transcriptome remains unknown. Using 15 RNA-sequencing datasets, encompassing almost 300 samples of various experimental setups, conditions and cell lines, we explore and classify the protein-coding transcriptome of CHO cells. Differences in cell line lineages are found to be the primary source of variation in transcribed genes. By employing a novel approach, we identified the core transcriptome that is ubiquitously expressed in all cell lines and culture conditions, as well as genes that remain entirely non-expressed. Additionally, we identified a set of genes that may be active or inactive depending on different conditions, which are linked to biological processes including translation as well as immune and stress response. Lastly, by integrating chromatin states derived from histone modifications, we provided additional context on the epigenetic level that supports our protein-coding gene classification. Our study offers a comprehensive insight into the CHO cell transcriptome and lays the foundation for future research into cellular adaptation to changing conditions and the development of phenotypes.