PT  - JOURNAL ARTICLE
AU  - Uri Keich
AU  - Kaipo Tamura
AU  - William Stafford Noble
TI  - An averaging strategy to reduce variability in target-decoy estimates of false discovery rate
AID  - 10.1101/440594
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 440594
4099  - http://biorxiv.org/content/early/2018/10/13/440594.short
4100  - http://biorxiv.org/content/early/2018/10/13/440594.full
AB  - Decoy database search with target-decoy competition (TDC) provides an intuitive, easy-to-implement method for estimating the false discovery rate (FDR) associated with spectrum identifications from shotgun proteomics data. However, the procedure can yield different results for a fixed dataset analyzed with different decoy databases, and this decoy-induced variability is particularly problematic for smaller FDR thresholds, datasets or databases. In such cases, the nominal FDR might be 1% but the true proportion of false discoveries might be 10%. The averaged TDC protocol combats this problem by exploiting multiple independently shuffled decoy databases to provide an FDR estimate with reduced variability. We provide a tutorial introduction to aTDC, describe an improved variant of the protocol that offers increased statistical power, and discuss how to deploy aTDC in practice using the Crux software toolkit.