The study of molecules based on their substructures is also widely applicable in cheminformatics. For many applications, lists of specific substructural patterns are compiled and matched against input structures, e.g., for indexing of structural databases to allow faster substructure searching , for the automatic detection of functional groups , or for molecular fingerprints based on pre-defined structural keys . Circular or spherical substructures are extracted from input molecules, i.e., fragments that each represent one atom and its neighbours up to a certain degree, to generate circular or path-based fingerprints , HOSE codes for computer-assisted structure elucidation (CASE) , and molecular signatures . Circular substructures can be used to assess and compare chemical diversity in a given data set or between multiple sets. For example, estimations can be made about the natural product-likeness of a compound by comparing its circular substructures to a curated data set of those frequently appearing in secondary metabolites or synthetic molecules . Another substructure concept frequently applied for chemical diversity assessment is the grouping of compounds by their molecular framework or scaffold. It is also used intuitively in combinatorial chemistry or drug design. Structural scaffold definitions in cheminformatics can be found in Murcko frameworks , scaffold trees , or scaffold networks , which are all based on ring systems and the linear substructures connecting them. For scaffold trees, Schuffenhauer et al. defined chemical rules to dissect molecular scaffolds into their characteristic smaller parent scaffolds that allow for hierarchical classification of compounds when placed in the scaffold tree . Such chemical expert rule systems can be grouped under the term "molecule fragmentation", i.e., algorithmic extraction of specific substructures from input molecules in silico. Another example is the Ertl algorithm for automated in silico FG detection in organic molecules , which overcomes the need for manually-curated lists of FG substructure patterns. With this approach, the complete diversity of functional groups can be studied and incorporated into chemical space mappings and molecular fragment descriptors . A similar algorithmic method was developed for the identification and removal of glycosidic moieties from organic molecules . The Sugar Removal Utility (SRU) can be used for deglycosylation as a preprocessing step in chemical space analyses and was also employed to document the diversity of sugar moieties in the largest open natural product (NP) database COCONUT .