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

Abstract

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.

Glycosylation as regulator of human B-cell leukaemias in bone marrow

“…An inherent limitation of analysis of bulk RNA expression data is that signals from cell types which constitute only a minor percentage of the total number may be lost. For example, BM stromal stem/progenitor cells constitute only around 0.001-0.01% of the total amount of BM cells (133). Since glycosyltransferase RNAs are not always highly expressed (134), bulk RNA sequencing is likely to therefore miss their expression in cell types with a low representation.…”

Finding Group Gene Biomarkers by improved LRP algoirthm and Intersection Selection Idea

“…Gene sequencing is of great value in disease screening [4][5][6][7], mechanism research [19][20][21], drug discovery [8][9][10] and other fields. The traditional methods, such as bioinformatics [22][23][30][31] and machine learning [26][27][28], etc.…”

Engineering Glyco‐Enzymes for Substrate Identification and Targeting

“…[6] Notwithstanding impressive advances in glycomics analysis, current knowledge of the size and composition of the human glycome remains incomplete, posing additional challenges for the interpretation of genetic and biochemical studies of glyco-enzyme function. [7] Glycosyltransferases transfer a single monosaccharide to a protein, peptide, and/or lipid target (Figure 1A) and are responsible for the biosynthesis of glycans. The expression, location, and specificity of these enzymes dictate the structure of glycans that are produced.…”