Hi David

So I reran with the changed parameter and the issue still seems to persist. 
I can share the updated results if you'd like as well? Also just confirming 
libra1 - 126, libra2 = 127N and so forth for a TMT10plex for example, since 
the issue is much aggravated in 2 out of three possible comparisons. To 
explain the setup more, yeast proteins are spiked with mammalian proteins 
such that yeast proteins are 10:4:1 (three replicates each) with mammalian 
proteins being (1:1:1) for the same.

Shagun

On Friday, March 25, 2022 at 6:02:55 PM UTC-4 Shagun Gupta wrote:

> Hi David
>
> Will do so, thank you! That makes a lot of sense. I have also added the 
> mzXML files but this might be the cause of the discrepancy I see!
>
> Thanks
> Shagun
>
> On Friday, March 25, 2022 at 4:42:46 PM UTC-4 David Shteynberg wrote:
>
>> Hello Shagun,
>>
>> I noticed in your condition file you are using TMT10 with the following 
>> masses:
>>  <reagent mz="126.127726" />
>>     <reagent mz="127.124761" />
>>     <reagent mz="127.131081" />
>>     <reagent mz="128.128116" />
>>     <reagent mz="128.134436" />
>>     <reagent mz="129.131471" />
>>     <reagent mz="129.137790" />
>>     <reagent mz="130.134825" />
>>     <reagent mz="130.141145" />
>>     <reagent mz="131.138180" />
>>
>>
>> The difference between neighboring channels is <0.01 at the lowest and 
>> yet you are using tolerance of 0.2:
>>
>> <massTolerance value="0.2" />
>>
>>
>> I think the appropriate mass tolerance for this type of labeling should 
>> be ~0.001.
>>
>> Does that make sense?  Please try running Libra with the mass tolerance 
>> appropriate for this type of label. 
>>
>> Cheers,
>> -David
>>
>> On Fri, Mar 25, 2022 at 10:34 AM Shagun Gupta <[email protected]> wrote:
>>
>>> Hi David
>>>
>>> Could you suggest a good email to reach you with? I can share the 
>>> pep.xml's and Libra condition file that way?
>>>
>>> -Shagun
>>>
>>> On Friday, March 25, 2022 at 11:00:38 AM UTC-4 David Shteynberg wrote:
>>>
>>>> Hello Shagun,
>>>>
>>>> Thank you for your email and interest in the TPP.  I have recently been 
>>>> comparing TMTPro analysis by ProteomeDiscoverer and Byonic to that 
>>>> produced 
>>>> by TPP's Libra.  As far as I can tell, when I run and compare the 
>>>> quantities (intensities) they are mostly the same between Libra (without 
>>>> isotopic impurity correction and 0 pseudocounts) and the 
>>>> ProteomeDiscoverer/Byonic.  Execution of Libra is defined in the 
>>>> conditions.xml file that has to be defined for each Libra run.  I would be 
>>>> happy to take a look at your data and analysis to see if it can be placed 
>>>> on the right path for the Libra analysis to work.  Please post your 
>>>> results 
>>>> somewhere I can download and test.
>>>>
>>>> Cheers,
>>>> -David
>>>>
>>>> On Fri, Mar 25, 2022 at 6:36 AM Shagun Gupta <[email protected]> 
>>>> wrote:
>>>>
>>>>> Hello
>>>>>
>>>>> Our lab has been trying to use Libra to quantify MS2 (Ion-trap) 
>>>>> identification and MS3-based quantification of TMT datasets and we were 
>>>>> trying to benchmark with an artificial yeast and mammalian spiked dataset 
>>>>> with known fold-change (FC) values. However we observe drastically 
>>>>> different values than expected, something we don't observe with other 
>>>>> search engines for the same dataset. 
>>>>>
>>>>> Has this issue been encountered before/ is there something obviously 
>>>>> wrong when running with TPP that might cause this? Happy to provide 
>>>>> further 
>>>>> details on the dataset and parameters used to run with (most of them 
>>>>> default apart from additions like static modification for TMT and 
>>>>> specification of MS3 for quantification among others).
>>>>>
>>>>> Thank you,
>>>>> Shagun
>>>>>
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