Tailor: A Nonparametric and Rapid Score Calibration Method for Database Search-Based Peptide Identification in Shotgun Proteomics

Abstract

Peptide-spectrum-match (PSM) scores used in database searching are calibrated to spectrum-or spectrumpeptide-specific null distributions. Some calibration methods rely on specific assumptions and use analytical models (e.g., binomial distributions), whereas other methods utilize exact empirical null distributions. The former may be inaccurate because of unjustified assumptions, while the latter are accurate, albeit computationally exhaustive. Here, we introduce a novel, nonparametric, heuristic PSM score calibration method, called Tailor, which calibrates PSM scores by dividing them with the top 100-quantile of the empirical, spectrum-specific null distributions (i.e., the score with an associated p-value of 0.01 at the tail, hence the name) observed during database searching. Tailor does not require any optimization steps or long calculations; it does not rely on any assumptions on the form of the score distribution (i.e., if it is, e.g., binomial); however, it relies on our empirical observation that the mean and the variance of the null distributions are correlated. In our benchmark, we re-calibrated the match scores of XCorr from Crux, HyperScore scores from X!Tandem, and the p-values from OMSSA with the Tailor method and obtained more spectrum annotations than with raw scores at any false discovery rate level. Moreover, Tailor provided slightly more annotations than E-values of X!Tandem and OMSSA and approached the performance of the computationally exhaustive exact p-value method for XCorr on spectrum data sets containing low-resolution fragmentation information (MS2) around 20−150 times faster. On high-resolution MS2 data sets, the Tailor method with XCorr achieved state-ofthe-art performance and produced more annotations than the well-calibrated residue-evidence (Res-ev) score around 50−80 times faster.

Spontaneous Isomerization of Asp387 in Tau is Diagnostic for Alzheimer’s Disease: An Endogenous Indicator of Reduced Autophagic Flux

“…All peptides and spectra from each 2-m/z isolation window were converted into matrices with Tailor calibrated XCorr as the values where each row is a potential peptide and each column is a spectrum. 75,76 All candidate peptides were filtered so they had at least one score above a given noise threshold, here we used a cutoff of 1.15 for the full proteome search and 1.1 for the smaller semi-tryptic search. Scores were baseline adjusted with simple subtraction so that the minimum score for each peptide was 0.…”

DIAmeter: matching peptides to data-independent acquisition mass spectrometry data

“…XCorr with Tailor calibration . The XCorr score is calibrated using the non-parametric Tailor calibration method ( Sulimov and Kertész-Farkas, 2020 ), by specifying the parameter –use-tailor-calibration T. In brief, for each edge , the Tailor method calibrates the score by dividing by the 99th quantile of the observed, spectrum-specific score distribution. Specifically, say that spectrum u is scored with respect to N candidate peptides, each with charge state c v , during the database search.…”

DIAmeter: Matching peptides to data-independent acquisition mass spectrometry data

“…The XCorr score is calibrated using the non-parametric Tailor calibration method, 27 by specifying the parameter . In brief, for each edge e = ( u,v ) ∈ E , the Tailor method calibrates the score XCorr u,v by dividing by the 99th quantile of the observed, spectrum-specific score distribution.…”

“…XCorr with Tailor calibration. The XCorr score is calibrated using the non-parametric Tailor calibration method, 27 by specifying the parameter --use-tailor-calibration T. In brief, for each edge e = (u, v) ∈ E, the Tailor method calibrates the score XCorr u,v by dividing by the 99th quantile of the observed, spectrum-specific score distribution. Specifically, say that spectrum u is scored with respect to N candidate peptides, each with charge state c v , during the database search.…”