Bjorn,

Thank you so very much that was extremely helpful! I'll be well on my way 
to finishing my analysis. 

-Robert M Jones

On Tuesday, February 18, 2014 6:45:24 AM UTC-7, Bjorn wrote:
>
> Hi,
> As far as I understand it, the TPP uses a mixture model-based approach to 
> determine posterior probabilities and it then uses these probabilities to 
> estimate the FDR. This can be done with or without the use of a decoy 
> database. However, when using some of the more sophisticated options (like 
> non-parametric modelling), you will need a decoy database to help the 
> modelling algorithms pin down the negative distribution. Also, when the 
> data is of not so excellent quality, the decoys can help make a better 
> distinction between good and bad identifications.
>
> After the analysis with ProteinProphet, you get something like this in the 
> ProteinProphet window:
>
> Prob Sens FPER Corr  Incorr
> 0.00 1.000 0.930 217 2874
> 0.10 1.000 0.337 217 110
> 0.20 1.000 0.337 217 110
> 0.30 0.915 0.216 198 55
> 0.40 0.865 0.152 187 34
> 0.50 0.816 0.102 177 20
> 0.60 0.777 0.074 168 14
> 0.70 0.747 0.058 162 10
> 0.80 0.647 0.019 140 3
> 0.90 0.608 0.010 132 1
> 0.95 0.569 0.005 123 1
> 0.96 0.547 0.004 119 0
> 0.97 0.529 0.003 115 0
> 0.98 0.507 0.002 110 0
> 0.99 0.470 0.001 102 0
> 1.00 0.152 0.000 33 0
>
> The FPER is your FDR, so if you decide to set it at 1%, you notice that 
> this corresponds with a probability cut off of 0.90. Now, in your protein 
> list, you accept all proteins with a prob. of 0.09 or higher, which is 
> estimated to be 132 correct ones and 1 incorrect protein. Everything below 
> is discarded.
>
> I found lots of info in the following papers (esp. the last paper). 
> Hope this helps!
> Cheers,
> Bjorn
>
> [1] Choi, H., Fermin, D., and Nesvizhskii, A. I. Significance analysis of 
> spectral count data in label-free shotgun proteomics. Mol. Cell. Proteomics 
> 7, 12 (2008), 2373–2385.
>
> [2] Choi, H., Ghosh, D., and Nesvizhskii, A. I. Statistical validation of 
> peptide identifications in large-scale proteomics using the target-decoy 
> database search strategy and flexible mixture modeling. J. Proteome Res. 7, 
> 1 (2008), 286–292.
>
> [3] Choi, H., and Nesvizhskii, A. I. False discovery rates and related 
> statistical concepts in mass spectrometry-based proteomics. J. Proteome 
> Res. 7, 1 (2008), 47–50.
>
> [4] Choi, H., and Nesvizhskii, A. I. Semisupervised model-based validation 
> of peptide identifications in mass spectrometry-based proteomics. J. 
> Proteome Res. 7, 1 (2008), 254–265.
>
> [5] Deutsch, E. W., Mendoza, L., Shteynberg, D., Farrah, T., Lam, H., 
> Tasman, N., Sun, Z., Nilsson, E., Pratt, B., Prazen, B., Eng, J. K., 
> Martin, D. B., Nesvizhskii, A. I., and Aebersold, R. A guided tour of the 
> Trans-Proteomic Pipeline. Proteomics 10, 6 (2010), 1150–1159.
>
> [6] Keller, A., Nesvizhskii, A. I., Kolker, E., and Aebersold, R. 
> Empirical statistical model to estimate the accuracy of peptide 
> identifications made by MS/MS and database search. Anal. Chem. 74, 20 
> (2002), 5383–5392.
>
> [7] Nesvizhskii, A. I. A survey of computational methods and error rate 
> estimation procedures for peptide and protein identification in shotgun 
> proteomics. J. Proteomics 73, 11 (2010), 2092–2123.
>

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