Improving the Results of De novo Peptide Identification via Tandem Mass Spectrometry Using a Genetic Programming-based Scoring Function for Re-ranking Peptide-Spectrum Matches

De novo peptide sequencing algorithms have been widely used in proteomics to analyse tandem mass spectra (MS/MS) and assign them to peptides, but quality-control methods to evaluate the confidence of de novo peptide sequencing are lagging behind. A fundamental part of a quality-control method is the scoring function used to evaluate the quality of peptide-spectrum matches (PSMs). Here, we propose a genetic programming (GP) based method, called GP-PSM, to learn a PSM scoring function for improving the rate of confident peptide identification from MS/MS data. The GP method learns from thousands of MS/MS spectra. Important characteristics about goodness of the matches are extracted from the learning set and incorporated into the GP scoring functions. We compare GP-PSM with two methods including Support Vector Regression (SVR) and Random Forest (RF). The GP method along with RF and SVR, each is used for post-processing the results of peptide identification by PEAKS, a commonly used de novo sequencing method. The results show that GP-PSM outperforms RF and SVR and discriminates accurately between correct and incorrect PSMs. It correctly assigns peptides to 10% more spectra on an evaluation dataset containing 120 MS/MS spectra and decreases the false positive rate (FPR) of peptide identification.