Group-walk: a rigorous approach to group-wise false discovery rate analysis by target-decoy competition

Jack Freestone, Temana Short, William Stafford Noble, Uri Keich

Abstract: Target-decoy competition (TDC) is a commonly used method for false discovery rate (FDR) control in the analysis of tandem mass spectrometry data. This type of competition-based FDR control has recently gained significant popularity in other fields after Barber and Candès laid its theoretical foundation in a more general setting that included the feature selection problem. In both cases, the competition is based on a head-to-head comparison between an (observed) target score and a corresponding decoy (knockoff) score. However, the effectiveness of TDC depends on whether the data are homogeneous, which is often not the case: in many settings, the data consist of groups with different score profiles or different proportions of true nulls. In such cases, applying TDC while ignoring the group structure often yields imbalanced lists of discoveries, where some groups might include relatively many false discoveries and other groups include relatively very few. On the other hand, as we show, the alternative approach of applying TDC separately to each group does not rigorously control the FDR.