Diagnosis of pancreatic cancer using targeted quantification of site-specific protein glycosylation

A method of training a model to diagnose a subject with respect to a pancreatic cancer (PC) disease state, the method comprising:

• receiving quantification data for a panel of peptide structures for a plurality of subjects,
• wherein the plurality of subjects includes a first portion diagnosed with a negative diagnosis of a PC disease state and a second portion diagnosed with a positive diagnosis of the PC disease state;
• wherein the quantification data comprises a plurality of peptide structure profiles for the plurality of subjects;
• and
• training a machine learning model using the quantification data to diagnose a biological sample with respect to the PC disease state using a group of peptide structures associated with the PC disease state,
• wherein the group of peptide structures is identified in Table 8;
• and
• wherein the group of peptide structures is listed in Table 8 with respect to relative significance to diagnosing the biological sample.

A method of monitoring a subject for a pancreatic cancer (PC) disease state, the method comprising:

• receiving first peptide structure data for a first biological sample obtained from a subject at a first timepoint;
• analyzing the first peptide structure data using a supervised machine learning model to generate a first disease indicator based on at least 3 peptide structures selected from a group of peptide structures identified in Table 8, wherein the group of peptide structures in Table 8 comprises a group of peptide structures associated with a PC disease state;
• receiving second peptide structure data of a second biological sample obtained from the subject at a second timepoint;
• analyzing the second peptide structure data using the supervised machine learning model to generate a second disease indicator based on the at least 3 peptide structures selected from the group of peptide structures identified in Table 8;
• and
• generating a diagnosis output based on the first disease indicator and the second disease indicator.

A composition comprising a peptide structure or a product ion, wherein:

• the peptide structure or the product ion comprises an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOS:
• 18, 21, 25, 28, 32, 51-67, corresponding to peptide structures PS-1 to PS-22 in Table 8;
• and
• the product ion is selected as one from a group consisting of product ions identified in Table 10 including product ions falling within an identified m/z range.

A composition comprising a glycopeptide structure selected as one from a group consisting of peptide structures PS-1 to PS-22 identified in Table 8, wherein:

• the glycopeptide structure comprises:
• an amino acid peptide sequence identified in Table 11 as corresponding to the glycopeptide structure;
• and
• a glycan structure identified in Table 13 as corresponding to the glycopeptide structure in which the glycan structure is linked to a residue of the amino acid peptide sequence at a corresponding position identified in Table 8;
• and
• wherein the glycan structure has a glycan composition.

A composition comprising a peptide structure selected as one from a plurality of peptide structures identified in Table 8, wherein:

• the peptide structure has a monoisotopic mass identified as corresponding to the peptide structure in Table 8;
• and
• the peptide structure comprises the amino acid sequence of SEQ ID NOs:
• 18, 21, 25, 28, 32, 51-67 identified in Table 18 as corresponding to the peptide structure.

A composition comprising a peptide structure or a product ion, wherein:

• the peptide structure or the product ion comprises an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOS:
• 18, 21, 25, 28, 32, 51-67;
• and
• the product ion is selected as one from a group consisting of product ions identified in Table 10 including product ions falling within an identified m/z range.

A composition comprising a glycopeptide structure selected as one from a group consisting of peptide structures PS-1 to PS-22 identified in Table 8, wherein:

• the glycopeptide structure comprises:
• an amino acid peptide sequence identified in Table 11 as corresponding to the glycopeptide structure;
• and
• a glycan structure identified in Table 6 as corresponding to the glycopeptide structure in which the glycan structure is linked to a residue of the amino acid peptide sequence at a corresponding position identified in Table 8;
• and
• wherein the glycan structure has a glycan composition.

A composition comprising a peptide structure selected as one of PS-1 to PS-22 peptide structures identified in Table 8, wherein:

• the peptide structure has a monoisotopic mass identified as corresponding to the peptide structure in Table 8;
• and
• the peptide structure comprises the amino acid sequence of SEQ ID NOS:
• 18, 21, 25, 28, 32, 51-67 identified in Table 8 as corresponding to the peptide structure.