Indeed the quantitation tools in the (specificall ASAPRatio and
XPRESS) TPP were originally developed over 10 years ago and were tuned
to perform with the instrum-entation of that time.

That said, options have been added over the past decade to allow
re-tuning the quantitation tools which will allow it to perform on
modern data.   Specifically, adjusting the mass tolerances, zeroing
out background estimates, using wavelet-based smoothing, using fixed
scan ranges and only identified charge-state precursor signal are all
possible in ASAPRatio which will allow it to perform similarly to
XPRESS, while making use of ProteinProphet's peptide to protein
mapping for protein quantitation (only ASAPRatio does this in TPP).

A good approach would identify the issues with the default settings of
ASAPRatio and rerun ASAPRatio a second time after identifying the
parameters that need to be adjusted.  If you have a specific
problematic dataset that you can share with me, I would be glad to
take a look at the issue and suggest a solution.

Cheers,

-David

On Tue, Dec 2, 2014 at 10:31 AM, Hannes Röst <[email protected]> wrote:
> Hi
>
> One way to combine search engines outside the MaxQuant environment with good
> quantification algorithms is the OpenMS package. This might be a sensible
> way to go if you like to combine multiple search eninges and the TPP search
> workflow with an alternative open-source quantification engine. I am not
> saying that it is the best but it might be worth a shot.
>
> Hannes
>
> On 2 December 2014 at 00:17, Alejandro <[email protected]> wrote:
>>
>> Hi Brian,
>>
>> Of what I have seen XPRESS does indeed performs better than ASAP with high
>> resolution data, plus it's incredible fast. Still, there's always the need
>> for QC. I also use MaxQuant, specially for multiplex isotopic data, but in
>> general one gets much more IDs using Xtandem (or combination of search
>> engines with Iprophet, something really helpful) than with Andromeda.
>>
>> Cheers,
>>
>> Alejandro
>>
>> On Monday, December 1, 2014 11:28:51 PM UTC+1, Brian Hampton wrote:
>>>
>>> It has been my experience that ASAPRatio is slow (haven't used 4.8 yet)
>>> and inaccurate even with high mass accuracy data.  I've used both chemical
>>> isotopic labeling and SILAC data sets and you really need to QC the results.
>>> The output of ASAPRatio is not to be trusted, based on my experience with
>>> it.  I've seen "interesting" hits have a given "interesting" ratio and then
>>> go back and look at the peak integrations and have occasionally found that
>>> after performing QC on the data that the ratio was reversed from what was
>>> originally reported by the algorithm!   This calls into question the
>>> accuracy of the entire dataset quantitation as performed by ASAPRatio.
>>>
>>> The original Aebersold paper on ASAPRatio is demonstrated on a reduced
>>> complexity dataset e.g. a pulldown.  The P-value was described as a way to
>>> quickly sort changed from unchanged compared to the background.  I am
>>> suspicious that ASAPRatio is just not that suited to datasets from complex
>>> samples like cell lysates et. al.  which is what I have been using it for
>>> and I suspect you have as well.
>>>
>>> I will begin use of XPRESS and see how that performs.  Given the need for
>>> quantification of proteomic data sets, I hope the TPP team is working on a
>>> better MS1 quan package than what is currently present in TPP.  It would be
>>> nice to see something more robust like Skyline but better suited to shotgun
>>> vs targeted quantification.  There is a paper describing ISOQUANT which
>>> looks promising but I believe it was originally written to handle SILAC only
>>> datasets.  Maybe the TPP developers can obtain this from the author and
>>> adapt it to handle multiple isotope labeling strategies and make it
>>> available to all their loyal TPP users who have benefited greatly by their
>>> efforts to date.
>>>
>>> Since you have high resolution data, have you tried MaxQuant?
>>>
>>> Cheers,
>>> Brian
>>>
>>> Brian Hampton
>>> Protein Analysis Lab
>>> Center for Vascular and Inflammatory Diseases
>>> University of Maryland School of Medicine
>>> 655 West Baltimore Street BRB 7-018
>>> Baltimore  MD  21201
>>> V: 410-706-8207
>>>
>>>
>>> On Mon, Dec 1, 2014 at 1:04 PM, Alejandro <[email protected]> wrote:
>>>>
>>>> A quick update.
>>>>
>>>> After running the same files with TPP 4.8, running time with ASAP ratio
>>>> is quite reduced, to ~1h, but quantitation seems to work better with 
>>>> XPRESS.
>>>>
>>>> Alejandro
>>>>
>>>> On Wednesday, November 19, 2014 7:29:30 PM UTC+1, Alejandro wrote:
>>>>>
>>>>> Hi all,
>>>>>
>>>>> I'm analyzing dimethylated data obtained with a QExactive using
>>>>> XTandem! (have tried both static or variable searches). If the data is
>>>>> quantified using Xpress, the time it takes is quite normal, ie fast,
>>>>> minute(s) or so for a 1GB RAW file (ca. 250MB mzXML), however when
>>>>> activating ASAPratio, the processing takes hundred times more than with
>>>>> Xpress (which reports a quite disperse distribution of ratios, not seen 
>>>>> with
>>>>> Orbitrap data, thus the reason to see how ASAP performs). After looking in
>>>>> the list I found a post which discussed somehow this
>>>>> https://groups.google.com/d/topic/spctools-discuss/TkkoHpXAh4A/discussion
>>>>> which was related to multithreading.
>>>>>
>>>>> When running this analysis the bottleneck seems to come from the
>>>>> ASAPratio:
>>>>>
>>>>> Stucked at:
>>>>>
>>>>> running: "C:/Inetpub/tpp-bin/XPressPeptideParser "interactasap.pep.xml"
>>>>> -m20 -a -nn,8.04437027 -nK,8.04437027 -H -c5"
>>>>> .................................................. 1k
>>>>> .................................................. 2k
>>>>> .................................................. 3k
>>>>> .................................................. 4k
>>>>> .................................................. 5k
>>>>> .................................................. 6k
>>>>> .................................................. 7k
>>>>> .
>>>>> command completed in 22 sec
>>>>>
>>>>> running: "C:/Inetpub/tpp-bin/ASAPRatioPeptideParser
>>>>> "interactasap.pep.xml" -lnK -C -r0.02"
>>>>>
>>>>>
>>>>> The same scenario as the one described in the old post seems to happen
>>>>> here, only one core and ~50MB usage of RAM, using only
>>>>> ASAPRatioPeptideParser.exe and this taking several hours to complete.
>>>>>
>>>>> Could it be also the mentioned "...redundant disk reads and base64
>>>>> decoding due to poor caching of the scans read from mzXML..." the cause? 
>>>>> Or
>>>>> it is just the nature of the data obtained with the Qexactive that makes 
>>>>> it
>>>>> take longer? I haven't checked if something would change by using an old
>>>>> version of ASAPRatio ~2009 from that post. Though I don't think this would
>>>>> be compatible with the current parsers.
>>>>>
>>>>> Any clues?
>>>>>
>>>>> Thanks,
>>>>>
>>>>> Alejandro
>>>>
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