PT - JOURNAL ARTICLE AU - Adriaan Sticker AU - Lennart Martens AU - Lieven Clement TI - Mass spectrometrists should search for all peptides, but assess only the ones they care about AID - 10.1101/094581 DP - 2017 Jan 01 TA - bioRxiv PG - 094581 4099 - http://biorxiv.org/content/early/2017/02/21/094581.short 4100 - http://biorxiv.org/content/early/2017/02/21/094581.full AB - In shotgun proteomics identified mass spectra that are deemed irrelevant to the scientific hypothesis are often discarded. Noble (2015)1 therefore urged researchers to remove irrelevant peptides from the database prior to searching to improve statistical power. We here however, argue that both the classical as well as Noble’s revised method produce suboptimal peptide identifications and have problems in controlling the false discovery rate (FDR). Instead, we show that searching for all expected peptides, and removing irrelevant peptides prior to FDR calculation results in more reliable identifications at controlled FDR level than the classical strategy that discards irrelevant peptides post FDR calculation, or than Noble’s strategy that discards irrelevant peptides prior to searching.