Patent ID: 11875880
Assignee: DH TECHNOLOGIES DEVELOPMENT PTE. LTD.
Field: Computer technology (Electrical engineering)
Classification: CPC G | IPC G

Claim 3:
4. A computer program product, comprising a tangible computer-readable storage medium whose contents include a program with instructions being executed on a processor so as to perform a method for calculating and recalculating protein confidence values by recalculating peptide confidence values in proteomic analysis in order to distinguish proteins found in a sample from random or false positive results, the method comprising:
(a) providing a system, wherein the system comprises distinct software modules, and wherein the distinct software modules comprise a measurement module and an analysis module;
(b) obtaining a plurality of spectra from one or more mass spectrometers that perform a plurality of scans of a sample that is proteolytically digested into surrogate peptide analytes producing a plurality of spectra using the measurement module;
(c) identifying a plurality of peptides from the plurality of spectra using the analysis module;
(d) searching a protein database for proteins matching peptides from the plurality of peptides producing a set of proteins and a corresponding set of peptides using the analysis module;
(e) determining peptide confidence values for the set of peptides using the analysis module, wherein a peptide confidence, Ci, of an ith peptide of the set of peptides is a probability that the ith peptide is identified from the plurality of spectra;
(f) calculating a protein confidence value for each protein in the set of proteins based on one or more peptide confidence values of one or more corresponding peptides from the set of peptides using the analysis module, wherein a protein confidence value Pp is a probability calculated according to

Pp=1−Π(1−Ci),

where Π(1−Ci) is the product of one or more peptide confidence values;
(g) selecting a protein from the set of proteins with a largest protein confidence value, saving the largest protein confidence value for the protein, removing the protein from the set of proteins, and removing one or more peptides corresponding to the protein from the set of peptides using the analysis module;
(h) recalculating the protein confidence value, Pp, for each protein in the set of proteins based on one or more peptide posterior probability values of one or more corresponding peptides from the set of peptides according to
Pp=1−Π(1−P(+|B)i) using the analysis module, wherein a posterior probability of the ithpeptide, P(+|B), of the set of peptides is calculated using, P
    ⁡
    
      (
      
        +
        
          |
          B
        
      
      )
    
  
  =
  
    
      
        P
        ⁡
        
          (
          
            B
            |
            +
          
          )
        
      
      ·
      
        P
        ⁡
        
          (
          +
          )
        
      
    
    
      P
      ⁡
      
        (
        B
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where P(B|+) is the peptide confidence value of the ith peptide, Ci, P(B) is the marginal probability of observing the peptide with a given confidence, and P(+) is the prior probability of randomly selecting a true positive and P(+) is calculated from all confidence values of peptides currently in the set of peptides and all confidence values of peptides removed from the set of peptides to account for the effect of removing the one or more peptides corresponding to the removed protein from the set of peptides, and
(i) repeating steps (f)-(g) until all proteins are removed from the set of proteins or until a protein confidence value of the selected protein with a largest protein confidence value is below a threshold of interest and identifies proteins found in the sample as the proteins with the saved largest protein confidence values using the analysis module.