A theoretical foundation of the target-decoy search strategy for false discovery rate control in proteomics

Understand

Motivation: Target-decoy search (TDS) is currently the most popular strategy for estimating and controlling the false discovery rate (FDR) of peptide identifications in mass spectrometry-based shotgun proteomics.

• While this strategy is very useful in practice and has been intensively studied empirically, its theoretical foundation has not yet been well established.
• Result: In this work, we systematically analyze the TDS strategy in a rigorous statistical sense.
• We prove that the commonly used concatenated TDS provides a conservative estimate of the FDR for any given score threshold, but it cannot rigorously control the FDR.