Apply an Enzyme to a Glycan — apply

This function simulates the action of an enzyme on a glycan. It returns all possible products generated by the enzyme with the given glycans.

Usage

apply_enzyme(glycans, enzyme, return_list = NULL, structure_level = "intact")

Arguments

glycans: A glyrepr::glycan_structure(), or a character vector of glycan structure strings supported by glyparse::auto_parse().
enzyme: An enzyme() or a gene symbol.
return_list: If NULL (default), return a list of glyrepr::glycan_structure() when glycans has length greater than 1, and a single glyrepr::glycan_structure() when glycans has length 1. Set to TRUE to always return a list. This can be useful when you are working programmatically with unknown input length. Note that when return_list = FALSE and length(glycans) > 1, an error will be thrown.
structure_level: Output structure level. "intact" keeps the current behavior and returns products with exact linkages. "topological" removes linkages from products while preserving residue identities. "partial" classifies inputs with incomplete linkage or anomer information; it is not a generated-output option. The requested level cannot be lower-resolution than the input glycans.

Value

A glyrepr::glycan_structure() vector, or a list of such vectors.

Important notes

Here are some important notes for all functions in the glyenzy package.

Applicability

Known-enzyme algorithms and enzyme information in glyenzy are applicable only to humans. Curated coverage is strongest for N-glycans and O-glycans and also includes selected glycosphingolipid headgroups and other glycan contexts. Lipid and protein aglycones are not represented, so glycolipid rules model the carbohydrate headgroup with ceramide omitted. Results may be inaccurate for unsupported glycan contexts or other species (e.g., plants, insects).

Inclusiveness

The algorithm takes an intentionally inclusive approach, assuming that all possible isoenzymes capable of catalyzing a given reaction may be involved. Therefore, results should be interpreted with caution.

For example, in humans, detection of the motif "Neu5Ac(a2-3)Gal(b1-" will return both "ST3GAL3" and "ST3GAL4". In reality, only one of them might be active, depending on factors such as tissue specificity.

Concrete glycans by default

Most functions only work for glycans containing concrete residues (e.g., "Glc", "GalNAc"), and not for glycans with generic residues (e.g., "Hex", "HexNAc"). Inputs with generic or mixed residues are supported where explicitly documented, such as trace_biosynthesis() and path_biosynthesis().

Substituents

Sulfate substituents are supported. Other substituents, such as phosphorylation and methylation, are not supported. Use glyrepr::remove_substituents() when unsupported substituents are present.

Incomplete or non-concrete glycan structures

If the glycan structure is incomplete, partially degraded, or contains generic or mixed residues, the result may be misleading. Glycans with a glyrepr::get_structure_level() other than "intact", or with a glyrepr::get_mono_type() other than "concrete", are matched with the lenient motif matching mode in glymotif. A warning is raised because enzyme predictions may be less reliable.

Starting points

For known-enzyme path inference:

For N-glycans, the starting structure is assumed to be "Glc(3)Man(9)GlcNAc(2)", the N-glycan precursor transferred to Asn by OST.
For O-GalNAc glycans, the starting structure is assumed to be "GalNAc(a1-".
For O-GlcNAc glycans, the starting structure is assumed to be "GlcNAc(b1-".
For O-Man glycans, the starting structure is assumed to be "Man(a1-".
For O-Fuc glycans, the starting structure is assumed to be "Fuc(a1-".
For O-Glc glycans, the starting structure is assumed to be "Glc(b1-".
For GlcCer glycans, the starting structure is assumed to be "Glc(b1-",
For GalCer glycans, the starting structure is assumed to be "Gal(b1-"

Examples

library(glyrepr)
library(glyparse)

# Use `glycan_structure()` and `enzyme()`
glycan <- auto_parse("GlcNAc(b1-2)Man(a1-3)[Man(a1-6)]Man(b1-4)GlcNAc(b1-4)GlcNAc(b1-")
apply_enzyme(glycan, enzyme("MGAT3"))
#> <glycan_structure[1]>
#> [1] GlcNAc(b1-2)Man(a1-3)[GlcNAc(b1-4)][Man(a1-6)]Man(b1-4)GlcNAc(b1-4)GlcNAc(b1-
#> # Unique structures: 1

# Or use characters directly
apply_enzyme("GlcNAc(b1-2)Man(a1-3)[Man(a1-6)]Man(b1-4)GlcNAc(b1-4)GlcNAc(b1-", "MGAT3")
#> <glycan_structure[1]>
#> [1] GlcNAc(b1-2)Man(a1-3)[GlcNAc(b1-4)][Man(a1-6)]Man(b1-4)GlcNAc(b1-4)GlcNAc(b1-
#> # Unique structures: 1

# Vectorized input
glycans <- c(
  "GlcNAc(b1-2)Man(a1-3)[Man(a1-6)]Man(b1-4)GlcNAc(b1-4)GlcNAc(b1-",
  "GlcNAc(b1-2)Man(a1-3)[GlcNAc(b1-2)Man(a1-6)]Man(b1-4)GlcNAc(b1-4)GlcNAc(b1-"
)
apply_enzyme(glycans, "MGAT3")
#> [[1]]
#> <glycan_structure[1]>
#> [1] GlcNAc(b1-2)Man(a1-3)[GlcNAc(b1-4)][Man(a1-6)]Man(b1-4)GlcNAc(b1-4)GlcNAc(b1-
#> # Unique structures: 1
#> 
#> [[2]]
#> <glycan_structure[1]>
#> [1] GlcNAc(b1-2)Man(a1-3)[GlcNAc(b1-4)][GlcNAc(b1-2)Man(a1-6)]Man(b1-4)GlcNAc(b1-4)GlcNAc(b1-
#> # Unique structures: 1
#>