Hierarchical levels of sialome complexity. The sialome can be analyzed at the following complexity levels: (A) sialic acid core and core modifications: esterification (with various groups), O-methylation, lactonization, or lactamization yielding >50 different structures; (B) linkage to the underlying sugar (three major and many minor linkages); (C) identity and arrangement of the underlying sugars that can also be further modified by fucosylation or sulfation; (D) glycan class (N-linked, O-linked or gangliosides [sialylated glycosphingolipids]); and (E) spatial organization of the Sia in sialylated microdomains, which have been referred to as “clustered saccharide patches” or “the glycosynapse.” (Reproduced, with permission, from Cohen M, Varki A. 2010. OMICS 14: 455–464.)