Precursor selection using an artificial intelligence algorithm increases proteomic sample coverage and reproducibility

A mass spectrometer system for analyzing an analyte in a sample, the system comprising:

• an ion source for generating ions from the analyte;
• first ion separation optics in communication with the ion source for separating ions according to their mass-to-charge ratios;
• ion fragmentation optics in communication with the first ion separation optics for generating product ions;
• a mass analyzer in communication with the ion fragmentation optics for separating ions according to their mass-to-charge ratios;
• wherein the mass analyzer comprises an ion detector for detecting ions separated according to their mass-to-charge ratios;
• a controller operably connected to the first and second ion separation optics, the first ion detector, and the ion fragmentation optics;
• wherein the controller comprises a memory module;
• and
• a chromatography column in communication with the ion source for fractionating the sample,
• wherein the controller controls the memory module, ion optics, mass analyzer and detector so as to:
• (a) receive a list of target analytes and target analyte product information into the memory module, wherein the list comprises from 25 to 5,000,000 target analytes;
• (b) provide a sample containing an analyte;
• (c) generate a distribution of precursor analyte ions from the sample;
• (d) fragment precursor analyte ions having a preselected distribution of mass-to-charge ratios, thereby generating product ions;
• (e) measure the mass-to-charge ratios of at least a portion of the product ions in the mass analyzer, wherein the mass analyzer has a mass accuracy of at least 1000 ppm, thereby generating product ion mass spectrometry data;
• (f) optimize analyte identification or quantitation during data acquisition by comparing the product ion mass spectrometry data to the list of target analytes and target analyte product information;
• (g) calculate a chromatography column elution order of the peptides in the list of target peptides and target peptide product information corresponding to one or more proteins, thereby generating an elution order list;
• (h) sort the elution order list from first eluting peptide to last eluting peptide, thereby generating a sorted elution order list;
• (i) fractionate the sample with the chromatography column prior to generating a distribution of precursor peptide ions from the sample;
• (j) identify target peptide product information in the product ion mass spectrometry data corresponding to a target peptide, thereby identifying a target peptide;
• (k) compare the identified target peptide to the sorted elution order list during data acquisition;
• and
• (l) identify one or more target peptides from the sorted elution order list which are within X peptides of the identified Peptide, wherein X is equal to 20% of the total number of target peptides in the elution order list, thereby generating a list of next predicted eluting peptides.

A method of identifying or quantifying an analyte in a sample using mass spectrometry, the method comprising:

• (a) providing a list of target peptides, wherein the target list comprises from 25 to 5,000,000 target peptides;
• (b) calculating a chromatography column elution order and elution time of the peptides in the list of target peptides, thereby generating an elution order list and predicted elution times for each target peptide;
• (c) sorting the elution order list from first eluting peptide to last eluting peptide, thereby generating a sorted elution order list;
• (d) providing a sample containing an analyte, wherein said analyte comprises peptides corresponding to one or more proteins;
• (e) generating a distribution of precursor analyte ions from the sample at elution times corresponding to the predicted elution times for the target peptides, wherein said analyte ions comprises peptide ions;
• (f) fragmenting precursor analyte ions having a preselected distribution of mass-to-charge ratios from at least a portion of the distribution of precursor analyte ions, thereby generating product ions;
• (g) measuring the mass-to-charge ratios of at least a portion of the product ions collected in a mass analyzer, wherein the mass analyzer has a mass accuracy of at least 1000 ppm, thereby generating product ion mass spectrometry data;
• and
• (h) identifying target peptides or peptide product information in the product ion mass spectrometry data corresponding to a target peptide by comparing the product ion mass spectrometry data to the list of target peptides and target peptide product information,
• thereby identifying or quantifying an analyte in the sample using mass spectrometry.