Mass Spectrometry

Abstract

The present invention is concerned with methods for the de novo sequencing of polypeptides from data obtained from mass spectrometry devices, particularly from (MS) n devices.

1 - 22 . (canceled) 
     
     
         23 . A method for determining at least one amino acid sequence for a sample polypeptide, the method being implemented in a computer comprising a memory storing processor readable instructions and a processor in communication with said memory, the method comprising:
 receiving, as input to the processor, a set of m/z peaks associated with a soft ionization mass spectrum obtained from said sample polypeptide, each of said m/z peaks having an associated m/z value;   identifying, by the processor, a plurality of m/z peak sets, each of said plurality of m/z peak sets corresponding to a possible amino acid sequence associated with the received set of m/z peaks;   processing, by the processor, said plurality of m/z peak sets using a reflective predicate filter to identify m/z peak sets;   discarding any identified m/z peak sets from said plurality of m/z peak sets; and   outputting said at least one amino acid sequence based upon said remaining plurality of m/z peak sets.   
     
     
         24 . The method of  claim 23 , wherein processing said plurality of m/z peak sets using a reflective predicate filter to identify m/z peak sets comprises, for each m/z peak set:
 comparing the possible amino acid sequence associated with the m/z peak set with possible amino acid sequences associated with other ones of the plurality of m/z peak sets in reverse order.   
     
     
         25 . The method of  claim 23 , wherein processing said plurality of m/z peak sets using a reflective predicate filter to identify m/z peak sets comprises:
 for each of said m/z peak sets:
 determining mass differences between each pair of neighbouring m/z peaks of the m/z peak set based upon the m/z values associated with each pair of m/z peaks; 
 determining a sequence of mass differences based upon the determined mass differences; and 
 determining a sequence of mass differences in reverse order based upon the determined mass differences; and 
   identifying m/z peak sets whose sequence of mass differences does not form at least part of a sequence of mass differences in reverse order of another of said m/z peak sets.   
     
     
         26 . The method of  claim 23 , wherein identifying a plurality of m/z peak sets, each of said plurality of m/z peak sets corresponding to a possible amino acid sequence associated with the received set of m/z peaks, comprises:
 determining a plurality of said received set of m/z peaks that each have an associated m/z value that differs from an m/z value associated with another of said plurality of said received set of m/z peaks by the mass of an amino acid.   
     
     
         27 . The method of  claim 23 , further comprising:
 identifying any m/z peak set which is a contiguous subsequence of another m/z peak set; and   discarding any identified m/z peak sets from the plurality of candidate m/z peak sets.   
     
     
         28 . The method of  claim 23 , further comprising:
 identifying candidate m/z peak sets in which mass differences between each m/z peak and at least one peak in the candidate m/z peak set having a closest m/z value above and/or below the peak correspond to that of a daughter ion or an end ion cluster; and   discarding any identified m/z peak sets from the plurality of candidate m/z peak sets.   
     
     
         29 . The method of  claim 23 , wherein outputting said at least one amino acid sequence based upon said remaining plurality of m/z peak sets comprises:
 for each of said remaining plurality of m/z peak sets, determining an amino acid sequence based upon a difference between m/z values associated with peaks of the m/z peak set.   
     
     
         30 . A computer program product for determining at least one amino acid sequence for a sample polypeptide, the computer program product comprising a non-transient computer usable medium having a computer readable program code, said computer readable program code comprising instructions arranged to cause a computer to:
 receive, as input to the processor, a set of m/z peaks associated with a soft ionization mass spectrum obtained from said sample polypeptide, each of said m/z peaks having an associated m/z value;   identify, by the processor, a plurality of m/z peak sets, each of said plurality of m/z peak sets corresponding to a possible amino acid sequence associated with the received set of m/z peaks;   process, by the processor, said plurality of m/z peak sets using a reflective predicate filter to identify m/z peak sets;   discard any identified m/z peak sets from said plurality of m/z peak sets; and   
       output said at least one amino acid sequence based upon said remaining plurality of m/z peak sets. 
     
     
         31 . The computer program product of  claim 30 , wherein processing said plurality of m/z peak sets using a reflective predicate filter to identify m/z peak sets comprises, for each m/z peak set:
 comparing the possible amino acid sequence associated with the m/z peak set with possible amino acid sequences associated with other ones of the plurality of m/z peak sets in reverse order.   
     
     
         32 . The computer program product of  claim 30 , wherein processing said plurality of m/z peak sets using a reflective predicate filter to identify m/z peak sets comprises:
 for each of said m/z peak sets:
 determining mass differences between each pair of neighbouring m/z peaks of the m/z peak set based upon the m/z values associated with each pair of m/z peaks; 
 determining a sequence of mass differences based upon the determined mass differences; and 
 determining a sequence of mass differences in reverse order based upon the determined mass differences; and 
   identifying m/z peak sets whose sequence of mass differences does not form at least part of a sequence of mass differences in reverse order of another of said m/z peak sets.   
     
     
         33 . The computer program product of  claim 30 , wherein identifying a plurality of m/z peak sets, each of said plurality of m/z peak sets corresponding to a possible amino acid sequence associated with the received set of m/z peaks, comprises:
 determining a plurality of said received set of m/z peaks that each have an associated m/z value that differs from an m/z value associated with another of said plurality of said received set of m/z peaks by the mass of an amino acid.   
     
     
         34 . The computer program product of  claim 30 , wherein said computer readable program code further comprises instructions arranged to cause a computer to:
 identifying any m/z peak set which is a contiguous subsequence of another m/z peak set; and   discarding any identified m/z peak sets from the plurality of candidate m/z peak sets.   
     
     
         35 . The computer program product of  claim 30 , further comprising:
 identifying candidate m/z peak sets in which mass differences between each m/z peak and at least one peak in the candidate m/z peak set having a closest m/z value above and/or below the peak correspond to that of a daughter ion or an end ion cluster; and   discarding any identified m/z peak sets from the plurality of candidate m/z peak sets.   
     
     
         36 . The computer program product of  claim 30 , wherein outputting said at least one amino acid sequence based upon said remaining plurality of m/z peak sets comprises:
 for each of said remaining plurality of m/z peak sets, determining an amino acid sequence based upon a difference between m/z values associated with peaks of the m/z peak set.   
     
     
         37 . A system for determining at least one amino acid sequence for a sample polypeptide, said system comprising:
 a memory storing processor readable instructions; and   a processor arranged to read and execute instructions stored in said memory;   wherein said processor readable instructions contain instructions to cause a computer to:   receive, as input to the processor, a set of m/z peaks associated with a soft ionization mass spectrum obtained from said sample polypeptide, each of said m/z peaks having an associated m/z value;   identify, by the processor, a plurality of m/z peak sets, each of said plurality of m/z peak sets corresponding to a possible amino acid sequence associated with the received set of m/z peaks;   process, by the processor, said plurality of m/z peak sets using a reflective predicate filter to identify m/z peak sets;   discard any identified m/z peak sets from said plurality of m/z peak sets; and   
       output said at least one amino acid sequence based upon said remaining plurality of m/z peak sets. 
     
     
         38 . The system of  claim 37 , wherein processing said plurality of m/z peak sets using a reflective predicate filter to identify m/z peak sets comprises, for each m/z peak set:
 comparing the possible amino acid sequence associated with the m/z peak set with possible amino acid sequences associated with other ones of the plurality of m/z peak sets in reverse order.   
     
     
         39 . The system of  claim 37 , wherein processing said plurality of m/z peak sets using a reflective predicate filter to identify m/z peak sets comprises:
 for each of said m/z peak sets:
 determining mass differences between each pair of neighbouring m/z peaks of the m/z peak set based upon the m/z values associated with each pair of m/z peaks; 
 determining a sequence of mass differences based upon the determined mass differences; and 
 determining a sequence of mass differences in reverse order based upon the determined mass differences; and 
   identifying m/z peak sets whose sequence of mass differences does not form at least part of a sequence of mass differences in reverse order of another of said m/z peak sets.   
     
     
         40 . The system of  claim 37 , wherein identifying a plurality of m/z peak sets, each of said plurality of m/z peak sets corresponding to a possible amino acid sequence associated with the received set of m/z peaks, comprises:
 determining a plurality of said received set of m/z peaks that each have an associated m/z value that differs from an m/z value associated with another of said plurality of said received set of m/z peaks by the mass of an amino acid.   
     
     
         41 . The system of  claim 37 , wherein said computer readable program code further comprises instructions arranged to cause a computer to:
 identifying any m/z peak set which is a contiguous subsequence of another m/z peak set; and   discarding any identified m/z peak sets from the plurality of candidate m/z peak sets.   
     
     
         42 . The system of  claim 37 , further comprising:
 identifying candidate m/z peak sets in which mass differences between each m/z peak and at least one peak in the candidate m/z peak set having a closest m/z value above and/or below the peak correspond to that of a daughter ion or an end ion cluster; and   discarding any identified m/z peak sets from the plurality of candidate m/z peak sets.   
     
     
         43 . The system of  claim 37 , wherein outputting said at least one amino acid sequence based upon said remaining plurality of m/z peak sets comprises:
 for each of said remaining plurality of m/z peak sets, determining an amino acid sequence based upon a difference between m/z values associated with peaks of the m/z peak set.