Find Synthesis Path Between Glycan Structures

Find a synthesis path from one glycan structure to another using enzymatic reactions. This function uses breadth-first search to find the shortest path or all possible paths within a given number of steps.

Usage

find_synthesis_path(from, to, enzymes = NULL, max_steps = 10, filter = NULL)

Arguments

from

A glyrepr::glycan_structure() scalar, or a character string supported by glyparse::auto_parse(). The starting glycan structure.

to

A glyrepr::glycan_structure() scalar, or a character string supported by glyparse::auto_parse(). The target glycan structure.

enzymes

A character vector of gene symbols, or a list of enzyme() objects. If NULL (default), all available enzymes will be used.

max_steps

Integer, maximum number of enzymatic steps to search. Default is 10.

filter

Optional function to filter generated glycans at each step. Should take a glyrepr::glycan_structure() vector as input and return a logical vector of the same length. It will be applied to all the generated glycans at each BFS step for pruning.

Value

An igraph::igraph() object representing the synthesis path(s). Vertices represent glycan structures with name attribute containing IUPAC-condensed strings. Edges represent enzymatic reactions with enzyme attribute containing gene symbols and step attribute indicating the step number.

Important notes

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

Applicability

All algorithms and enzyme information in glyenzy are applicable only to humans, and specifically to N-glycans and O-GalNAc glycans. Results may be inaccurate for other types of glycans (e.g., GAGs, glycolipids) or for glycans in 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.

Only "concrete" glycans

The function only works for glycans containing concrete residues (e.g., "Glc", "GalNAc"), and not for glycans with generic residues (e.g., "Hex", "HexNAc").

Substituents

Subtituents (e.g. sulfation, phosphorylation) is not supported yet, and the algorithms might fail for glycans with subtituents. If your glycans contains substituents, use glyrepr::remove_substituents() to get clean glycans.

Incomplete glycan structures

If the glycan structure is incomplete or partially degraded, the result may be misleading.

Starting points

Throughout glyenzy, the starting glycan is the Glc(3)Man(9)GlcNAc(2) precursor for N-glycans, and GalNAc(a1- for O-glycans. This means that enzymes involved in N-glycan precursor biosynthesis, mainly ALGs, and OST, which transfered the precursor to Asn, are not considered here. Similarly, GALNTs for O-glycans are not considered.

Examples

library(glyrepr)
library(glyparse)

# Find shortest path
from <- "Gal(b1-4)GlcNAc(b1-"
to <- "Neu5Ac(a2-6)Gal(b1-4)GlcNAc(b1-"
path <- find_synthesis_path(from, to, enzymes = "ST6GAL1", max_steps = 3)

# View the path
igraph::as_data_frame(path, what = "edges")
#>                  from                              to  enzyme step
#> 1 Gal(b1-4)GlcNAc(b1- Neu5Ac(a2-6)Gal(b1-4)GlcNAc(b1- ST6GAL1    1