Bridging Glycomics and Genomics: New Uses of Functional Genetics in the Study of Cellular Glycosylation

All living cells are coated with a diverse collection of carbohydrate molecules called glycans. Glycans are key regulators of cell behavior and important therapeutic targets for human disease. Unlike proteins, glycans are not directly templated by discrete genes. Instead, they are produced through multi-gene pathways that generate a heterogenous array of glycoprotein and glycolipid antigens on the cell surface. This genetic complexity has sometimes made it challenging to understand how glycosylation is regulated and how it becomes altered in disease. Recent years, however, have seen the emergence of powerful new functional genomics technologies that allow high-throughput characterization of genetically complex cellular phenotypes. In this review, we discuss how these techniques are now being applied to achieve a deeper understanding of glyco-genomic regulation. We highlight specifically how methods like ChIP-seq, RNA-seq, CRISPR genomic screening and scRNA-seq are being used to map the genomic basis for various cell-surface glycosylation states in normal and diseased cell types. We also offer a perspective on how emerging functional genomics technologies are likely to create further opportunities for studying cellular glycobiology in the future. Taken together, we hope this review serves as a primer to recent developments at the glycomics-genomics interface.