Tailor: non-parametric 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 spectrum-peptide-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, non-parametric, heuristic PSM score calibration method, called Tailor, which calibrates PSM scores by dividing it 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, it works with any score functions with high- and low-resolution information. 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 Tailor method, and obtained more spectrum annotation 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 datasets containing low-resolution fragmentation information (MS2) around 20-150 times faster. On high-resolution MS2 datasets, the Tailor method with XCorr achieved state-of-the-art performance, and produced more annotations than the well-calibrated Res-ev score around 50-80 times faster.\n\nGraphical TOC Entry\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC=\"FIGDIR/small/831776v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (9K):\norg.highwire.dtl.DTLVardef@10e13cdorg.highwire.dtl.DTLVardef@13638e5org.highwire.dtl.DTLVardef@d17e81org.highwire.dtl.DTLVardef@1c86552_HPS_FORMAT_FIGEXP M_FIG C_FIG