Glycan Core Alignment
Introduction
Glycan core alignment requires motif structures align with at least one connected substructure (subtree) at the reducing end of the glycan. Aligned motif and glycan monosaccharides and glycosidic linkages must respect the matching rules outlined below. A core 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.
In addition, non-strict alignments permit additional phosphate and sulfate substituents on glycan monosaccharides and alditol modifications at the reducing end of the glycan, even when the motif does not indicate them. When ambiguity in glycan topology permits at least one motif-to-core alignment, the motif and glycan are considered to have a non-strict alignment. Strict motif alignments in the determined topology portion of an undetermined topology glycan are considered strict.
Glycan core alignment is often used to characterize glycans by the structure of their reducing end. In particular, (non-strict) core alignment is used for GlyGen glycan classification motifs.
Glycan core alignment is the default alignment strategy for motifs that have a reducing-end annotation of true.
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, except for glycan reducing-end alditol.
| 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 |
Yes, non-strict alignment. The base monosaccharides are the same, and all modifications except for the alditol modification are the same in the same position. The additional alditol at the reducing end of an uncyclized glycan is permitted, even if not specified on the motif monosaccharide. |
|
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, with additional glycan phosphate and sulfate substituents permitted.
| 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 |
Yes, non-strict alignment. The base monosaccharides are the same, and all substituents except for the phosphate are the same with the same linkage. The additional glycan phosphate is permitted, even if not indicated on the motif monosaccharide. |
|
a-dgal-HEX-1:5||(2d:1)n-acetyl |
a-dgal-HEX-1:5||(2d:1)n-acetyl|(6o:1)sulfate |
Yes, non-strict alignment. The base monosaccharides are the same, and all substituents except for the sulfate are the same with the same linkage. The additional glycan sulfate is permitted, even if not indicated on the motif monosaccharide. |
|
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 other than phosphate or sulfate. |
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 | Core Alignment? |
|---|---|---|
|
Yes, strict alignment. At least one substructure at the reducing end of the glycan (lower arm) aligns with the motif, with glycan anomeric configurations and parent glycosidic bond positions contained in the corresoponding motif values. | ||
|
Yes, non-strict alignment. At least one substructure at the reducing end of the glycan (upper arm) aligns with the motif, with non-empty intersection between anomeric configurations and parent glycosidic bond positions. | ||
| Motif | Glycan | Core Alignment? |
|
No. The motif does not align at the reducing end of the glycan. The motif does permit a strict substructure alignment at the nonreducing-end of the glycan. |
See Also
Nonreducing-End Alignment, Substructure Alignment, Whole-Glycan Alignment.