Indeed, the availability of de novo FDR control procedures would have significant implications beyond the comparative evaluation of different sequencing methods. In practice, users of any de novo sequencing algorithm need to establish a threshold in the ranked list of predictions produced by the method. This can be achieved by selecting a score threshold corresponding to a target precision, as measured using a gold standard from the database search . However, such thresholds are likely to be overly optimistic, for the reasons outlined above.