Whole-Glycan Alignment

Introduction

Whole-glycan alignment requires motif structures align with the entire glycan. Aligned motif and glycan monosaccharides and glycosidic linkages must respect the matching rules outlined below. A whole-glycan alignment may be strict, when all resolutions of missing and undetermined glycan details are consistent with the motif. Non-strict alignments require at least one resolution of missing and undetermined glycan details be consistent with the motif. All monosaccharide or glycosidic bond comparisons must be consistent with strict alignment for the alignment to be considered strict.

Additional phosphate and sulfate substituents on glycan monosaccharides and alditol modifications at the reducing end of the glycan are NOT permitted, unlike non-strict alignments for other alignment strategies. When ambiguity in glycan topology permits at least one motif-to-whole-glycan alignment, the motif and glycan are considered to have a non-strict alignment.

Whole-glycan alignment is primarily used to assign semantic names to specific glycan structures.

Currently, whole-glycan alignments are only used in the GlyGen motif collection.

Monosaccharide Comparison

Each specific characteristic (anomeric configuration, etc.) of the glycan and motif monosaccharides are considered to be sets. Missing characteristics represent a set containing all possible values. For a strict alignment, glycan monosaccharide characteristics must be contained in (or, a subset of) the corresponding motif monosaccharide characteristics. For a non-strict alignment, glycan monosaccharide characteristics must have an non-empty intersection with the corresponding motif monosaccharide characteristics.

Since monosaccharide characteristics either have a single value or are missing, we can simplify the above rules as follows:

1. have the same number of carbon atoms (HEX, PENT, etc.); and

2. have the same stem-type (Man, Glc, etc.), if the motif monosaccharide stem-type is specified; and

3. have the same orientation (D-type, L-type), if the motif monosaccharide orientation is specified.

For a strict alignment, aligned motif and glycan monosaccharides must also:

4a. have the same ring information (1:5, etc.), if the motif monosaccharide ring information is specified; and

5a. have the same anomeric configuration (α, β), if the motif monosaccharide anomeric configuration is specified.

For a non-strict alignment, aligned motif and glycan monosaccharides must also:

4b. have the same ring information (1:5, etc.), if the glycan and motif monosaccharide ring information are specified; and

5b. have the same anomeric configuration (α, β), if the glycan and motif monosaccharide anomeric configuration are specified.

Motif Monosaccharide	Structure Monosaccharide	Alignment?
b-dglc-HEX-1:5	b-dglc-HEX-1:5	Yes. The monosaccharides are identical.
x-dglc-HEX-1:5	a-dglc-HEX-1:5	Yes, strict alignment. All monosaccharide properties are the same, except for anomeric configuration. The motif monosaccharide anomeric configuration contains the glycan monosaccharide's value.
b-dglc-HEX-1:5	x-dglc-HEX-1:5	Yes, non-strict alignment. The motif monosaccharide anomeric configuration is specified and the glycan monosaccharide anomeric configuration includes this value.
b-dglc-HEX-1:5	a-dglc-HEX-1:5	No. The both the motif and glycan monosaccharide anomeric configuration is specified and they are not the same.
x-dglc-HEX-x:x	a-dglc-HEX-1:5	Yes, strict alignment. Most monosaccharide properties are the same, with the exception of anomeric configuration and the ring information. The motif monosaccharide anomeric configuration and ring information are not specified, so the glycan monosaccharide characteristics are contained in the motif monosaccharide characteristics.

For a strict alignment, aligned motif and glycan monosaccharides must:

6a. have the same modifications (deoxygenation, carbonyl, etc.) at the same position.

For a non-strict alignment, aligned motif and glycan monosaccharides must:

6b. have the same modifications (deoxygenation, carbonyl, etc.) at the same position.

Motif Monosaccharide	Structure Monosaccharide	Alignment?
b-dglc-HEX-1:5	b-dglc-HEX-1:5	Yes. The monosaccharides are identical, neither has any modifications.
b-dglc-HEX-1:5|6:d	b-dglc-HEX-1:5|6:d	Yes, strict alignment. The base monosaccharides are the same, with the same modification at the same position.
b-dglc-HEX-1:5|3:d	b-dglc-HEX-1:5|6:d	No. The base monosaccharides are the same, but the modification is not in the same position.
b-dglc-HEX-1:5|6:d	b-dglc-HEX-1:5|6:a	No. The base monosaccharides are the same, but the modifications are different.
b-dglc-HEX-1:5|3:d	b-dglc-HEX-1:5|3:d|6:d	No. The base monosaccharides are the same, but the glycan monosaccharide has an additional modification.
b-dglc-HEX-1:5|1:aldi	b-dglc-HEX-1:5|1:aldi	Yes, strict alignment. The base monosaccharides are the same, with the same modification at the same position.
b-dglc-HEX-1:5	b-dglc-HEX-1:5|1:aldi	No. The base monosaccharides are the same, but the glycan monosaccharide has an additional modification.
b-dglc-HEX-1:5|1:aldi	b-dglc-HEX-1:5	No. The base monosaccharides are the same, but the motif monosaccharide has an additional modification missing from the glycan monosaccharide.

For a strict alignment, aligned motif and glycan monosaccharides must:

7a. have the same substituents (N-acetyl, phosphate, sulfate, etc.) with the same linkage.

For a non-strict alignment, aligned motif and glycan monosaccharides must:

7b. have the same substituents (N-acetyl, phosphate, sulfate, etc.) with the same linkage.

Motif Monosaccharide	Structure Monosaccharide	Alignment?
b-dglc-HEX-1:5	b-dglc-HEX-1:5	Yes, strict alignment. The monosaccharides are identical, neither has any substituents.
a-dgal-HEX-1:5||(2d:1)n-acetyl	a-dgal-HEX-1:5||(2d:1)n-acetyl	Yes, strict alignment. The base monosaccharides are the same, with the same substituent with the same linkage.
x-dgal-HEX-1:5||(2d:1)n-acetyl	a-dgal-HEX-1:5||(2d:1)n-acetyl	Yes, strict alignment. The base monosaccharides are the same, except for anomeric configuration, which is missing for the motif monosaccharide. Each monosaccharide has the same substituent with the same linkage.
a-dgal-HEX-1:5||(4d:1)n-acetyl	a-dgal-HEX-1:5||(2d:1)n-acetyl	No. The base monosaccharides are the same, with the same substituent, but with different linkage.
a-dgal-HEX-1:5||(2d:1)n-acetyl	a-dgal-HEX-1:5||(2d:1)n-acetyl|(6o:1)phosphate	No. The base monosaccharides are the same, but the glycan monosaccharide has an additional substituent.
a-dgal-HEX-1:5||(2d:1)n-acetyl	a-dgal-HEX-1:5||(2d:1)n-acetyl|(6o:1)sulfate	No. The base monosaccharides are the same, but the glycan monosaccharide has an additional substituent.
a-dgal-HEX-1:5||(2d:1)n-acetyl|(6o:1)sulfate	a-dgal-HEX-1:5||(2d:1)n-acetyl	No. The base monosaccharides are the same, but the motif monosaccharide has an additional substituent missing from the glycan monosaccharide.
a-dgal-HEX-1:5	a-dgal-HEX-1:5||(2d:1)n-acetyl	No. The base monosaccharides are the same, but the glycan monosaccharide has an additional substituent.

Glycosidic Bond Comparison

Each specific characteristic of the aligned glycosidic bonds attaching a child monosaccharide to a parent monosaccharides are considered to be sets. Missing characteristics represent a set containing all possible values. For a strict alignment, glycan glycosidic bond characteristics must be contained in (or, a subset of) the corresponding glycosidic bond monosaccharide characteristics. For a non-strict alignment, glycan glycosidic bond characteristics must have an non-empty intersection with the corresponding motif glycosidic bond characteristics.

Since linkage type and child linkage position typically are either specified with a single value or are missing, we can simplify the above statements as follows:

For a strict alignment, aligned motif and glycan glycosidic bonds attaching a child monosaccharide to a parent monosaccharide must:

1a. have the same child linkage type (n,d,...), if the motif glycosidic bond child linkage type is specified; and

2a. have the same child linkage position (1,2,...), if the motif glycosidic bond child linkage position is specified; and

3a. have the same parent linkage type (d,o,...), if the motif glycosidic bond parent linkage type is specified; and

4a. have the glycan parent linkage positions (2,3,4,5,6,...) be a subset of the motif glycosidic bond parent linkage position.

For a non-strict alignment, aligned motif and glycan glycosidic bonds attaching a child monosaccharide to a parent monosaccharide must:

1b. have the same child linkage type (n,d,...), if the motif and glycan glycosidic bond child linkage type are specified; and

2b. have the same child linkage position (1,2,...), if the motif glycosidic bond child linkage position are specified; and

3b. have the same parent linkage type (d,o,...), if the motif glycosidic bond parent linkage type are specified; and

4b. have the glycan parent linkage positions (2,3,4,5,6,...) have non-empty intersection with the motif glycosidic bond parent linkage positions.

Motif Linkage	Structure Linkage	Alignment?
o(3+1)d	o(3+1)d	Yes, strict alignment. Identical linkages.
o(-1+1)d	o(3+1)d	Yes, strict alignment. All linkage properties specified in the motif linkage contain the properties in the glycan linkage.
o(3+1)d	o(3+-1)d	Yes, non-strict alignment. Glycan child linkage positions have non-empty intersection with motif child linkage positions.
o(2+1)d	o(2|4+1)d	Yes, non-strict alignment. Glycan parent linkage positions have non-empty intersection with motif parent linkage positions.
o(2+1)d	o(-1+1)d	Yes, non-strict alignment. Glycan parent linkage positions have non-empty intersection with motif parent linkage positions.
o(4|6+1)d	o(2|4+1)d	Yes, non-strict alignment. Glycan parent linkage positions have non-empty intersection with motif parent linkage positions.
o(-1+1)d	o(2|4+1)d	Yes, strict alignment. Glycan parent linkage positions are contained in the motif parent linkage positions.

Examples

Motif	Glycan	Whole-Glycan Alignment?
GGM.000071	G57710SU	Yes, strict alignment. Motif and glycan are identical.
GGM.000074	G56133NW	Yes, strict alignment. Motif and glycan are identical.
GGM.000074	G30925QW	Yes, strict alignment. Motif does not specify reducing-end anomeric configuration, so any glycan reducing-end anomeric configuration is permitted.
GGM.000071	G19926LY	Yes, non-strict alignment. Glycan reducing end anomeric configuration has non-empty intersection with motif reducing end anomeric configuration.
Motif	Glycan	Whole-Glycan Alignment?
GGM.000071	G76657BK	No. Glycan has additional monosaccharides. The motif does have a strict glycan core and a strict substructure alignment to the glycan.
GGM.000071	G30925QW	No. Glycan has an additional sulfate substituent. The motif does have a non-strict glycan core, a non-strict nonreducing-end, and a non-strict substructure alignment to the glycan.

See Also

Glycan Core Alignment, Nonreducing-End Alignment, Substructure Alignment.