A consensus-based and readable extension of Li near Co de for R eaction R ules (LiCoRR)

Abstract

Systems glycobiology aims to provide models and analysis tools that account for the biosynthesis, regulation, and interactions with glycoconjugates. To facilitate these methods, there is a need for a clear glycan representation accessible to both computers and humans. Linear Code, a linearized and readily parsable glycan structure representation, is such a language. For this reason, Linear Code was adapted to represent reaction rules, but the syntax has drifted from its original description to accommodate new and originally unforeseen challenges. Here, we delineate the consensuses and inconsistencies that have arisen through this adaptation. We recommend options for a consensus-based extension of Linear Code that can be used for reaction rule specification going forward. Through this extension and specification of Linear Code to reaction rules, we aim to minimize inconsistent symbology thereby making glycan database queries easier. With a clear guide for generating reaction rule descriptions, glycan synthesis models will be more interoperable and reproducible thereby moving glycoinformatics closer to compliance with FAIR standards. Here, we present Linear Code for Reaction Rules (LiCoRR), version 1.0, an unambiguous representation for describing glycosylation reactions in both literature and code.

Keywords: glycoinformatics; linear code; systems glycobiology.

Figure 1

Common terminology and anatomy of a theoretical glycan, (KJ(IH)GF(D(E)(C)B)A. In this figure, we demonstrate some key terminology as well as the three primary uncertainty operators: branch (orange), continuation (blue), and ligand (green). The structures matching these terms are shown in matching colors, those matching both the continuation and ligand are shown in purple. A ligand can typically be removed with one cut. A continuation is a connection from a node to a root that can “continue” or “bypasses” other branch points. The paths from I to G or K to G represent one continuation; to represent both paths, a continuation is necessary because traversing from I to G requires the syntactic “bypass” of the KJ branch.

Figure 2

Monosaccharide reachability analysis. (A) Clusters contain monosaccharides with highly similar stereochemistry (>80%). (B) The maximum common substructure (MCS) associated with each cluster. (C) An example to illustrate the modifications needed to reach one monosaccharide to another, as identified by the complete monosaccharide reachability network (Table S6, Supporting Information File 1). (D) The monosaccharides reachability network, showing only connectivity for the least number of modifications needed, differentiated by color as stated in the legend, between monosaccharides (circle) and clusters (diamond). Additionally, the node size denotes the number of different possible paths taken for them to be reached. Please note that each edge is not a predicted or proposed feasible reaction. Edges denote functional groups that can be added or removed from one monosaccharide to represent another.