Trace a Virtual Biosynthetic Path of Glycans
trace_biosynthesis_virtual.RdReconstruct every structure-driven biosynthetic path for one or more
glycans by trimming terminal residues and sulfate groups backward. Unlike
trace_biosynthesis(), this does not require known enzyme rules.
Arguments
- glycans
A
glyrepr::glycan_structure()vector, or a character vector of strings supported byglyparse::auto_parse(). Can also be a single glycan. If multiple glycans are provided, the starting structure will be decided by the first glycan. Therefore, please make sureglycansare not of mixed glycan types.- enzymes
A character vector of concrete gene symbols or abstract activity names, or a list of
enzyme()objects. Concrete and abstract enzymes cannot be mixed. Used only whenannotate_enzymesisTRUE; ifNULL, all available concrete enzymes are considered.- annotate_enzymes
Whether to annotate each virtual transition with concrete enzymes whose rules can perform it. Defaults to
FALSE.
Value
A glyenzy_virtual_biosynthesis_network object inheriting from
glyenzy_biosynthesis_network and igraph::igraph(). Vertices contain
IUPAC-condensed strings in name and a logical target attribute indicating
whether each vertex is a target glycan. At most one directed edge connects
each substrate and product. Edges have a forward step, is_virtual = TRUE,
a virtual-enzyme enzyme label, and a list-valued enzymes attribute. When
annotate_enzymes is TRUE, enzymes contains every candidate concrete
enzyme for each transition; otherwise each element is empty.
Virtual enzymes
Each edge is named for the residue added by that step. Intact glycans include
the linkage anomer and acceptor position, so a beta-1,4-linked GlcNAc is
labeled "b4GlcNAcT". Topological glycans omit linkage
information and use "GlcNAcT". Generic topological glycans use
their preserved generic residue names, such as "HexNAcT".
Sulfation is represented as its own atomic transition. Sulfate additions at
positions 3 and 6 use "3SulfoT" and "6SulfoT"; an unknown or other
position uses "?SulfoT". A sulfated terminal residue is therefore
desulfated before the residue itself can be trimmed.
Virtual tracing starts N-glycans at the N-glycan core and all other glycans
at their reducing-end root residue. Sulfates are removed from these
automatically selected starts. In path_biosynthesis_virtual(), the
explicit from glycan is always the virtual starting structure, including
any sulfate groups it contains; those sulfates must also occur in to.
These networks represent structural possibilities rather than biological
feasibility.
Generic structures do not retain glycan-class metadata. A generic structure
matching the N-glycan-core topology is therefore assumed to be an N-glycan;
use path_biosynthesis_virtual() with an explicit from when that topology
belongs to another glycan class.
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 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
Some functions accept glycan structures that are incomplete, partially
degraded, or contain generic residues. When accepted, 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-"
Input compatibility
trace_biosynthesis(), trace_biosynthesis_virtual(),
path_biosynthesis(), and path_biosynthesis_virtual() accept only
glycans that share one monosaccharide type ("concrete" or "generic")
and one structure level ("intact" or "topological"). Structures with
mixed generic and concrete residues, partial structures, and missing
structures are not supported. In the path_*() functions, from and to
must have the same monosaccharide type and structure level.
Use glyrepr::convert_to_generic() to standardize monosaccharide types or
glyrepr::remove_linkages() to standardize structures at the topological
level.