These days, Percolator is the gold standard for separating good peptide MS/MS matches from bad ones. Is it perfect? No, but it is darned good at its job.
The problem with Percolator, however, is that it is assessing your peptide spectral matches with for something like 18 different criteria (list here) and this takes time...sometimes a massive amount of time. But we are getting used to the power of Percolator, particularly as more limitations of much simpler (and way faster!) false discovery rate approaches such as target-decoy become apparent.
Whats the solution? Maybe is NOKOI. If you Google it, you'll have to tell the search engine 20 times that "No...I do NOT mean Nokia..." NOKOI comes to us from some great researchers in Belgium and is described in this new JPR paper from Giulia Gonnelli et. al.,
I recently saw a great talk on how this works. I'd rather not spoil the surprises in this great paper (or show how bad I actually am at maths...). Suffice to say, the data looks really good. Results almost as good as Percolator when used in conjunction with Mascot, but without nearly so severe a bottleneck in processing capabilities.
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