Systems and methods for sequencing carbohydrates

A system for obtaining information useful for sequencing oligosaccharides, comprising;

• a spectrum screener, including:
• a peak picking engine for selecting an ion mass from mass spectral data obtained from profiling an oligosaccharide sample in a mass spectrometer, and
• a composition mapping engine for mapping the ion mass to a set of one or more
• monosaccharide units, wherein the combined mass of the monosaccharide units when joined to form an oligosaccharide is consistent with the corresponding ion mass of the oligosaccharide;
• a topology processor capable of receiving the set of one or more monosaccharide units, the topology processor comprising:
• at least one data structure having at least one data field containing sequence information for one or more monosaccharide units from the set of one or more monosaccharide units,
• an inference database including at least one inference rule, and
• a constraint algorithm module for applying the at least one inference rule to the set of one or more monosaccharide units and updating the at least one data structure;
• wherein the at least one data structure includes information useful for sequencing oligosaccharides.

A computer system for use in determining structural information about an oligosaccharide, comprising computer instructions for:

• providing a set of one or more monosaccharide units that make up at least a portion of the oligosaccharide;
• populating at least one data structure for the one or more monosaccharide units, wherein the at least one data structure includes at least one data field containing sequence information for the one or more monosaccharides;
• iteratively:
• applying an inference rule to the one or more monosaccharide units, and
• updating the at least one data structure by modifying the sequence information in the at least one data field based, at least in part, on an inference deduced from applying the inference rule;
• and
• determining structural information about the oligosaccharide from the updated data structure, or
• a computer-readable medium storing a computer program executable by a plurality of server computers, the computer program comprising computer instructions for:
• providing a set of one or more monosaccharide units that make up at least a portion of the oligosaccharide;
• populating at least one data structure for the one or more monosaccharide units, wherein the at least one data structure includes at least one data field containing sequence information for the one or more monosaccharide units;
• iteratively:
• applying an inference rule to the set of one or more monosaccharide units, and
• updating the at least one data structure by modifying the sequence information in the at least one data field based, at least in part, on an inference deduced from applying the inference rule;
• and
• determining structural information about the oligosaccharide from the updated data structure.

A method for resolving the structure of an oligosaccharide, comprising:

• receiving a plurality of sets of mass spectral data obtained from sequential mass spectrometry of an oligosaccharide;
• automatically selecting one or more fragmentation pathways from the plurality of sets of mass spectral data, each fragmentation pathway having a set of ion masses corresponding to fragments of the oligosaccharide;
• identifying one or more monosaccharide units that make up at least a portion of the oligosaccharide from the one or more fragmentation pathways;
• and
• resolving a structure of the oligosaccharide by iteratively applying one or more inference rules to the one or more monosaccharide units to refine a structural relationship between the one or more monosaccharide units.

A method of detecting the presence of isomers of an oligosaccharide in a sample, comprising:

• receiving a plurality of sets of mass spectral data obtained from sequential mass spectrometry of the sample;
• receiving a set of expected oligosaccharides, each having sequence information;
• selecting a first set of fragmentation pathways from the plurality of sets of mass spectral data, each fragmentation pathway in the first set having ion masses corresponding to fragments of an oligosaccharide in the sample;
• generating a second set of fragmentation pathways, from the first set, that are consistent with the set of expected oligosaccharides such that fragmentation of each of the set of expected oligosaccharides occurs along at least one of the fragmentation pathways in the second set;
• and
• detecting the presence of isomers based on the existence of fragmentation pathways in the first set that are not in the second set;
• or
• a method of resolving the structure of an oligosaccharide, comprising:
• performing sequential mass spectrometry of an oligosaccharide, including
• generating a set of mass spectral data for a fragmentation step,
• automatically selecting an ion mass in the set of mass spectral data, and
• performing further fragmentations of the selected ion mass;
• generating a fragmentation pathway having ion masses corresponding to ion masses of successive fragments of the oligosaccharide;
• and
• resolving a structure of the oligosaccharide by iteratively applying one or more inference rules to the fragments along the fragmentation pathway;
• wherein automatically selecting an ion mass includes selecting an ion mass based at least on its intensity in the mass spectral data and at least one of an associated type of fragmentation and elemental composition of the oligosaccharide.