Next-generation bioprocess: an industry perspective of how the ‘omics era will affect future biotherapeutic development

Abstract

The past decade has seen significant instrumentation and methodological advances enabling much broader profiling of metabolites, proteins and nucleic acids. This in turn has been leveraged to enhance our sophistication and understanding of Chinese hamster ovary (CHO) cell metabolism in a bio processing environment. Of the three aforementioned fields, genomics has established itself as the preeminent technology platform for the foreseeable future largely due to a combination of throughput, comprehensive coverage and a relatively simple workflow. This has come to pass as a result of the tremendous advancements in nextgeneration sequencing (NGS) technology. These breakthroughs have lowered the barriers of cost and time associated with whole genome (DNA-Seq) and transcriptome (RNA-Seq) sequencing projects at an unprecedented rate, giving way to the ‘sequencing revolution’ [1]. The era of CHO genomics was ushered in by Xu and co-workers who applied NGS technology to create the first publically available CHO-K1 draft genome in 2011 [2]. CHO-K1 is but one of a handful of CHO host cell lines utilized by the bioprocessing industry. Indeed considering the extended time in culture and variety of adaptation strategies applied by the numerous labs working with CHO, every CHO host should be considered a unique cell line, irrespective of a shared common lineage [3]. Therefore, in subsequent publications by Lewis et al. [4] and Brinkrolf et al. [5] the CHO-K1 draft genome was expanded upon by sequencing the Chinese hamster genome. Having a Chinese hamster reference genome to facilitate the assembly of additional CHO genomes will benefit the community as a whole. However, the work is far from done as the quality of the genome is curtailed by gaps in sequencing coverage and incomplete gene annotations. A community of scientists working with CHOgenome.org is currently in the process of updating and correcting the CHO/hamster draft genomes, with particular interest in the sequencing gaps and annotations. This work will be critical to unlock the full benefits of having a high-quality genome to work with. Acknowledging the work that remains, the question becomes: how will NGS impact future bioprocess and what is the potential role of other ‘omics platforms?