Thank you very much Eric for the insights. I think the MQ search uses 
decoys too and search parameters are almost similar, at least they are not 
more relaxed for MQ. I am not sure about the behavior of PEP and the tiny 
peaks after the highest confidence and that is something that I need to 
investigate more carefully.

I have another unrelated question which I am going to ask in another topic.

Sincerely,
Ali

On Wednesday, January 4, 2017 at 6:28:24 PM UTC-5, Eric Deutsch wrote:
>
> Hi Ali, my thoughts are that for this dataset and analysis, 
> PeptideProphet+iProphet (PP+iP) are discriminating between correct and 
> incorrect  much better than the other analysis. The vast majority of 
> peptides are deemed by PP+iP as very likely to be correct or very likely 
> incorrect with a rather small population of IDs at intermediate confidence. 
> The other analysis seems to be unsure about many more. In fact the curve is 
> extremely steep indicating not very good discriminating power between 
> correct and incorrect. There are many more in the intermediate range.
>
>  
>
> The PP+iP analysis looks quite similar to what we are used to for modern 
> datasets. The steepness of the other analysis seems a bit worrying to me. 
> How are the PEPs calculated? Can you perform an independent analysis of the 
> PEPs to see if they agree with decoys or some other measure of errors? I 
> would say that in the range that matters (FDR < 1%) PP+iP is giving you a 
> better result. It is puzzling that the total number of correct hits at FDR 
> 2.5% is so much lower fir PP+iP. I couldn’t say from the data shown why 
> that is. Maybe the PEPs are not correct or MQ is finding more IDs because 
> of different search parameters? I don’t know.
>
>  
>
> Regards,
>
> Eric
>
>  
>
>  
>
> *From:* Ali [mailto:[email protected] <javascript:>] 
> *Sent:* Wednesday, January 04, 2017 1:06 PM
> *To:* spctools-discuss
> *Cc:* [email protected] <javascript:>; 
> [email protected] <javascript:>
> *Subject:* Re: [spctools-discuss] PeptideProphet/iProphet Probability 
> Distribution
>
>  
>
>  
>
>  
>
> Dear Eric and David
>
>  
>
> By accepting lower thresholds I actually mean accepting higher FDRs but 
> that is not so useful here because there is not so many hits after the very 
> high probabilities and I will not be gaining much by using lower 
> thresholds. PeptideProphet gives me a lot of PSMs with very high confidence 
> and very low FDR. But as I allow higher FDRs like 2-3% it falls behind PEP 
> from MaxQuant.
>
>  
>
> Here is another plot to better show my point. I have compared the combined 
> results above with Max Quant's results as I increase the FDR. As it can be 
> seen, number of unique peptides is more with PepPro/iPro for low FDR, but 
> in the end it falls behind PEP.
>
>  
>
>  
>
>
> <https://lh3.googleusercontent.com/-VZgUOiAvvno/WG1ggpOR3uI/AAAAAAAABBA/nyrjsBbLrGQ60eo3iqB3beMOVs4ZCXCAACLcB/s1600/Picture1.png>
>
>  
>
> And this can be understood from the following plot:
>
>  
>
>
> <https://lh3.googleusercontent.com/-jmsbfmBfbXA/WG1hNLP8e1I/AAAAAAAABBI/SBnRc5-naTw09vjKk0K4m9xcCBgS-1Z8QCLcB/s1600/Picture2.png>
>
>  
>
> Do you have any thoughts on this?
>
>  
>
> Thank you very much,
>
> Ali
>
>  
>
>
>
> On Wednesday, January 4, 2017 at 3:08:14 PM UTC-5, Ali wrote:
>
> Dear David and Eric
>
>  
>
> Thanks for your replies and suggestions. I thought that I might be able to 
> increase identification by accepting hits with lower thresholds. I do 
> understand what you mentioned here.
>
>  
>
> Thanks again,
>
> Ali
>
> On Tuesday, January 3, 2017 at 1:57:38 PM UTC-5, Eric Deutsch wrote:
>
> In the ideal case where the PeptideProphet and iProphet had perfect 
> discriminating power, i.e. the correct and incorrect PSM distributions do 
> not overlap, you would expect a large peak at P=0 and P=1 and nothing in 
> between. As a dataset diverges from this ideal and the correct and 
> incorrect distributions begin to overlap, you will still have very large 
> peaks near P=0 and near P=1, with a small number of intermediate values 
> where the probability is between 0 and 1.
>
>  
>
> So, in short, your distribution is exactly what you would expect based on 
> what you did. It is indicative of a great dataset. You should follow 
> David’s suggestion, and then if you replot, you will see huge peaks at 0 
> and 1 with rather little in between.
>
>  
>
> Regards,
>
> Eric
>
>  
>
>  
>
> *From:* [email protected] [mailto:[email protected]] 
> *On Behalf Of *David Shteynberg
> *Sent:* Tuesday, January 03, 2017 10:36 AM
> *To:* spctools-discuss
> *Subject:* Re: [spctools-discuss] PeptideProphet/iProphet Probability 
> Distribution
>
>  
>
> These results are showing you that iProphet has great discriminating power 
> even when you restrict the input to only non-low probability PSMs 
> (filtering with PeptideProphet probability).  The best way to run iProphet 
> is to give it all the data from PeptideProphet (use a PeptideProphet 
> minimum probability of 0).
>
>  
>
> -David
>
>  
>
> On Mon, Jan 2, 2017 at 9:26 PM, Ali <[email protected]> wrote:
>
> Dear all
>
>  
>
> I am plotting the distribution of the assigned PeptideProphet and iProphet 
> probabilities to my search results. I am seeing a rather strange pattern 
> shown below. Why am I seeing so many hits with very high confidence 
> (probability >0.98) but suddenly after that threshold the number of 
> assigned probabilities to the PSMs decrease abruptly? What could be the 
> reason for this pattern? One would expect to see all ranges of 
> probabilities for PSMs.
>
>  
>
>
> <https://lh3.googleusercontent.com/-BeikGpozjkw/WGsygFV83UI/AAAAAAAABAg/DcG6lRxucM4IRclvdadal-eFSaA05sd6QCLcB/s1600/Picture1.png>
>
>  
>
>  
>
> This figure is the combination of different search engines:
>
> - Comet (min PepPro=0.5)
>
> - X! Tandem GPM (min PepPro=0.05)
>
> - X! Tandem TPP (min PepPro=0.05)
>
>  
>
> The horizontal axis is between 0.5 and 1.
>
>  
>
> and I can see the same pattern for the PeptideProphet distribution of each 
> one of these search engine results including SpectraST (Except for X! 
> Tandem GPM).
>
>  
>
> Thank you very much,
>
>  
>
> Ali
>
>  
>
>  
>
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