crux calibrate-scores

Usage:

crux calibrate-scores [options] <search results> <column name>

Description:

Given a collection of scored peptide-spectrum matches (PSMs), estimate two statistical confidence measures for each: a q-value and a posterior error probability (PEP).

q-value

The q-value is analogous to a p-value but incorporates false discovery rate multiple testing correction. The q-value associated with a score threshold T is defined as the minimal false discovery rate at which a score of T is deemed significant. In this setting, the q-value accounts for the fact that we are analyzing a large collection of PSMs.

To estimate q-values, calibrate-scores searches the input directory for a corresponding set of decoy PSMs. The false discovery rate associated with a given score is estimated as the number of decoy scores above the threshold divided by the number of target scores above the threshold, multiplied by the ratio of the total number of targets to total number of decoys. This methodology is described in the following article:

Lukas Käll, John D. Storey, Michael J. MacCoss and William Stafford Noble. "Assigning significance to peptides identified by tandem mass spectrometry using decoy databases." Journal of Proteome Research. 7(1):29-34, 2008.
Note that calibrate-scores does not (yet) estimate the percentage of incorrect targets, as described in the above article. Hence, the method implemented here as "decoy q-values" is analogous to the "Simple FDR" procedure shown in Figure 4A of the above article.

In each case, the estimated FDRs are converted to q-values by ranking the PSMs by score and then taking, for each PSM, the minimum of the current FDR and all of the FDRs below it in the ranked list.

Posterior error probability

Unlike the q-value, which is calculated with respect to the collection of PSMs with scores above a specified threshold, the PEP (also known in the literature as the "local FDR") is calculated with respect to a single score. The PEP is the probability that a particular PSM is incorrect. Crux's PEPs are estimated using the methodology described in this article:

Lukas Käll, John Storey and William Stafford Noble. "Non-parametric estimation of posterior error probabilities associated with peptides identified by tandem mass spectrometry." Bioinformatics (Proceedings of the ECCB). 24(16):i42-i48, 2008.

A primer on multiple testing correction can be found here:

William Stafford Noble. "How does multiple testing correction work?" Nature Biotechnology. 27(12):1135-1137, 2009.

A discussion of q-values versus posterior error probabilities is provided in this article:

Lukas Käll, John D. Storey, Michael J. MacCoss and William Stafford Noble. "Posterior error probabilities and false discovery rates: two sides of the same coin." Journal of Proteome Research. 7(1):40-44, 2008.

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