Building a Combinatorial Glycan Hypothesis
- glycresoft build-hypothesis glycan-combinatorial
- Example Usage

Building a Combinatorial Glycan Hypothesis¶

When you do not have a complete list of glycan compositions you know are reasonable and present, a first pass can be done with a combinatorial glycan composition hypothesis.

A combinatorial glycan hypothesis is defined by a set of component ranges and a set of algebraic constraints.

A component range is defined by a component residue such as a monossaccharide (or any entity which can be encoded with IUPAClite Monosaccharide and Glycan Notation) with a minimum count and a maximum count. Candidate glycan compositions will contain the component with every possible value in the range between minimum and maximum

An algebraic constraint is defined by two expressions containing numbers binary arithmetic operators and variables corresponding to components and a comparator operator relating the two expressions. No candidate glycan composition will be included in the hypothesis will fail to satisfy all applied constraints.

HexNAc > (NeuAc + NeuGc + 1)

This constraint requires that the total number of sialylic acids always be one less than the number of HexNAc, which is common for canonical N-glycans in humans.

To pass these instructions to the build tool, they must be written in a text file following the format

; comments are allowed on lines starting with a semi-colon
<component>  <minimum>  <maximum>
<component>  <minimum>  <maximum>
...
; a blank line separates the component range rules from the constraints

<expression> <operator> <expression>
<expression> <operator> <expression>
...

Warning

Due to the average size of a combinatorial search space and limitations of composition motifs, glycan compositions produced by this program are only checked for being N-glycans, and as such you cannot tag compositions O-glycans directly with this tool at this time. This restriction is wholly artificial and may be removed in the future. For more information on glycan composition classifiers, please see Glycan Composition Classes.

glycresoft build-hypothesis glycan-combinatorial¶

glycresoft build-hypothesis glycan-combinatorial [OPTIONS] RULE_FILE
                                                 DATABASE_CONNECTION

Options

-r, --reduction <string>¶: Reducing end modification

-d, --derivatization <string>¶: Chemical derivatization to apply

-n, --name <string>¶: The name for the hypothesis to be created

-c, --glycan-type <choice>¶: The glycan classification to apply to all generated glycan compositions. If not set, a heuristic will be used to guess if a composition in an N-glycan. This is only relevant when building a glycopeptide hypothesis.

Choices: [

n-glycan; o-glycan; gag-linker]

Arguments

RULE_FILE¶: Required argument <path>

DATABASE_CONNECTION¶: Required argument <string> A connection URI for a database, or a path on the file system

For more information on reductions and derivatizations, please see Glycan Modifications

Example Usage¶

$ cat rules-file.txt
Hex 3 10
HexNAc 2 9
Fuc 0 5
Neu5Ac 0 4

Fuc < HexNAc
HexNAc > NeuAc + 1

$ glycresoft build-hypothesis glycan-combinatorial rules-file.txt combinatorial-database -n "Combinatorial Human N-Glycans"
Building Glycan Hypothesis Combinatorial Human N-Glycans
13:12:06 - glycresoft:log:175 - INFO - Begin Combinatorial Glycan Hypothesis Serializer
{'derivatization': None,
 'engine': Engine(sqlite:///combinatorial-database),
 'glycan_file': u'rules-file.txt',
 'loader': None,
 'reduction': None,
 'start_time': datetime.datetime(2017, 8, 31, 13, 12, 6, 105000),
 'status': 'started',
 'transformer': None,
 'uuid': '459bffe3d9fd42019eb202c7afb3f72f'}
13:12:06 - glycresoft:log:175 - INFO - Generating Glycan Compositions from Symbolic Rules for GlycanHypothesis(id=1, name=Combinatorial Human N-Glycans)
13:12:08 - glycresoft:log:175 - INFO - 1000 glycan compositions created
13:12:09 - glycresoft:log:175 - INFO - Generated 1280 glycan compositions
13:12:09 - glycresoft:log:175 - INFO - Hypothesis Completed
13:12:09 - glycresoft:log:175 - INFO - End Combinatorial Glycan Hypothesis Serializer
13:12:09 - glycresoft:log:175 - INFO - Started at 2017-08-31 13:12:06.105000.
Ended at 2017-08-31 13:12:09.047000.
Total time elapsed: 0:00:02.942000
CombinatorialGlycanHypothesisSerializer completed successfully.

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