The Sialome—Far More Than the Sum of Its Parts

The glycome is defined as the glycan repertoire of cells, tissues, and organisms, as found under specified conditions. The vastly diverse glycome is generated by a nontemplate driven biosynthesis, which is indirectly encoded in the genome, and very dynamic. Due to this overwhelming diversity, glycomic analysis must be approached at different hierarchical levels of complexity. In this review five such levels of complexity and the experimental approaches used for analysis at each level are discussed for a subclass of the glycome: the sialome. The sialome, in analogy to the canopy of a forest, covers the cell membrane with diverse array of complex sialylated structures. Sialome complexity includes modification of sialic acid core structure (the leaves and flowers), the linkage to the underlying sugar (the stems), the identity, and arrangement of the underlying glycans (the branches), the structural attributes of the underlying glycans (the trees), and finally, the spatial organization of the sialoglycans in relation to components of the intact cell surface (the forest). Understanding the full complexity of the sialome thus requires combined analyses at multiple levels, that is, the sialome is far more than the sum of its parts.