Data Independent Acquisition of Product Ion Spectra and Reference Spectra Library Matching

Abstract

Systems and methods are disclosed for detecting compounds in a sample using a tandem mass spectrometer. A sample comprising a plurality of detectable compounds that have been separated in time over a time interval is introduced into a tandem mass spectrometer. A sample product ion spectra is obtained. The presence of one or more known compounds of interest in the sample product ion spectra is determined. A compound is identified as present in the sample if the score associated with said compound meets a threshold value set as indicative of the likely presence of the compound in the sample.

What is claimed is: 
     
         1 . A method for detecting compounds in a sample using a tandem mass spectrometer, comprising:
 (a) introducing into a tandem mass spectrometer a sample comprising a plurality of detectable compounds that have been separated in time over a time interval;   (b) obtaining a sample product ion spectra by:
 (1) selecting precursor ions for transmittal using a plurality of precursor ion mass selection windows for each time step of a plurality of time steps of the time interval; and 
 (2) performing at each time step for each precursor ion mass selection window a plurality of product ion scans to generate the sample product ion spectra; 
   (c) determining the presence of one or more known compounds of interest in the sample product ion spectra by:
 (1) comparing the sample product ion spectra corresponding to a specific precursor ion mass selection window expected to contain a precursor ion corresponding to the known product ion spectra to a known product ion spectra for the precursor ion; and 
 (2) calculating a score that represents how well known product ions of the known product ion spectra and sample product ions of the sample product ion spectra match, and 
   (d) identifying a compound as present in the sample the score associated with said compound meets a threshold value set as indicative of the likely presence of the compound in the sample.   
     
     
         2 . The method of  claim 1 , wherein the mass selection window has a width greater than about 10 amu. 
     
     
         3 . The method of  claim 1 , wherein the known compounds comprise one or more of peptides, proteins, complete proteomes, endogenous metabolites, lipids, carbohydrates, or combinations thereof. 
     
     
         4 . The method of  claim 1 , wherein the known compounds comprise one or more compounds of pharmaceutical, environmental, forensic, or industrial importance. 
     
     
         5 . The method of  claim 1 , wherein the known product ion spectra are determined from authentic standards of the known compounds, from an analysis of samples containing the compounds, from existing spectral libraries, or computationally generated by applying empirical or a priori fragmentation or modification rules to the known compounds. 
     
     
         6 . The method of  claim 1 , wherein a sample product ion with a score that meets a threshold value set as indicative of the likely presence of the compound in the sample is considered a matching sample product ion and using one or more matching sample product ions to identify a modified form of one or more compounds of the known compounds. 
     
     
         7 . The method of  claim 6 , further comprising comparing the matching sample ions to masses predicted from known product ions and a modification to characterize a type and location of the modification. 
     
     
         8 . The method of  claim 6 , further comprising extracting a spectrum of the identified modified form from the sample product ion spectra in order to characterize a type and location of the modification in the identified modified form.