Protein Inference and FDR: Why 1% at the Peptide Level Is Not 1% at the Protein Level

A bottom-up proteomics experiment digests proteins into peptides, discards the protein-level context, measures the peptides, then reconstructs which proteins were present. That reconstruction isn't bookkeeping — peptides map to proteins many-to-many, and recovering a protein list means choosing among explanations the data doesn't fully distinguish. Parsimony resolves it with a rule, not a measurement. And the "1% FDR" in most methods sections controls the peptide layer, not the protein one: Mascot's own documentation shows a 1% sequence FDR yielding 4.55% protein FDR in the same search. The gap grows as experiments get larger.