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Determine Whether a Glycan Is Synthesized by a Given Enzyme

have_enzyme.Rd

Glycans are produced through a series of enzymatic reactions. This function checks whether a specific enzyme participates in the biosynthesis of a given glycan (or glycans).

Usage

have_enzyme(glycans, enzyme, method = c("motif", "path"))

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.

method

Method used to infer enzyme involvement. "motif" checks product motifs directly in each glycan. "path" extracts enzymes from trace_biosynthesis() results, which is more accurate but slower.

Value

A logical vector of the same length as glycans.

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-"

Algorithm

The overall approach is straightforward: for each reaction rule associated with the enzyme, the function checks whether the corresponding product motif appears in the glycan. If any rule matches, the function returns TRUE.

For N-glycans, additional logic is applied to handle special cases. Products of MGAT1 are often further trimmed by glycoside hydrolases, meaning that the final glycan product may no longer contain the original motif. In these cases, the function instead looks for specific motif markers to determine enzyme involvement.

Examples

library(glyrepr)
library(glyparse)

# Use `glycan_structure()` and `enzyme()`
glycan <- auto_parse("Neu5Ac(a2-6)Gal(b1-4)GlcNAc(b1-")
have_enzyme(glycan, enzyme("ST6GAL1"))
#> [1] TRUE

# Or use characters directly
have_enzyme("Neu5Ac(a2-6)Gal(b1-4)GlcNAc(b1-", "ST6GAL1")
#> [1] TRUE

# Vectorized input
glycans <- c(
  "Neu5Ac(a2-6)Gal(b1-4)GlcNAc(b1-",
  "Gal(b1-4)GlcNAc(b1-"
)
have_enzyme(glycans, "ST6GAL1")
#> [1]  TRUE FALSE

# Use reconstructed biosynthesis paths
have_enzyme(glycans, "ST6GAL1", method = "path")
#> [1]  TRUE FALSE