Fantastic. Thanks David, I'll try this out.

Cheers,
Ben

On Wed, May 5, 2010 at 5:22 PM, dctrud <[email protected]> wrote:

> Ben,
>
> There are two separate searches, one with light mods static, one with
> heavy mods static. We use a front-end to the TPP which does all the
> steps, including translating unimod PTM specifications into search
> engine mods, so I've just run a test and looked up exactly what Tandem
> is using. These searches also use fixed Carbamidomethyl (C) and
> variable Oxidation (M).
>
> Light Search
> <note type="input" label="residue, modification mass">28.0...@k,
> 28.0...@[,57.0...@c,</note>
> <note type="input" label="residue, potential modification
> mass">15.9...@m,</note>
>
> Heavy Search
> <note type="input" label="residue, modification mass">32.0...@k,
> 32.0...@[,57.0...@c,</note>
> <note type="input" label="residue, potential modification
> mass">15.9...@m,</note>
>
> The output from the searches is combined using xinteract. The
> ASAPRatio command lines are:
>
> /wwwdata/pipeline/live/extern/tpp_4.3.1/bin/ASAPRatioPeptideParser
> 'interact.pep.xml.gz' -lnK -S -r0.02
> /wwwdata/pipeline/live/extern/tpp_4.3.1/bin/
> ASAPRatioProteinRatioParser 'interact.prot.xml.gz'
> /wwwdata/pipeline/live/extern/tpp_4.3.1/bin/ASAPRatioPvalueParser
> 'interact.prot.xml.gz'
>
> Cheers,
>
> --
> Dr. David Trudgian
> Bioinformatician in Proteomics
> University of Oxford
>
> Mon-Thu: CCMP, Roosevelt Drive
> Tel: (+44) (01865 2)87784
>
> Friday : Dunn School of Pathology, S. Parks Rd.
> Tel: (+44) (01865 2)75557
>
>
> On 5 May, 16:35, Ben Collins <[email protected]> wrote:
> > Hi DT,
> >
> > I'm trying to use dimethylation labelled samples with TPP but I think
> > I might not be specifying the modifications correctly. Is there any
> > chance that you could post the relevant sections from your search
> > params file (preferably X!Tandem if you're using this)?
> >
> > Many thanks,
> > Ben
> >
> > On Mar 19, 11:10 am, dctrud <[email protected]> wrote:
> >
> >
> >
> > > Bernard,
> >
> > > Sorry for the slow reply. ASAPRatio will know which label is heaviest,
> > > it shouldn't matter which way around the searches are.
> >
> > > With regard to the questions r.e.dimethylfalse positives, the
> > > procedure we are using this for involves labeling for quantitation
> > > where all lysines should be dimethylated / heavy dimethylated. I
> > > probably wrongly assumed you were doing this labeling, whereas I guess
> > > you are not forcing complete dimethylation of lysines? What exactly is
> > > your experiment? What biological changes are you trying to measure?
> >
> > > DT
> >
> > > On 11 Mar, 17:59, Bernt <[email protected]> wrote:
> >
> > > > Hi DT,
> >
> > > > Really grateful for your advice. I get what you mean, I have 2 more
> > > > concerns: can we change which form to be the numerator and which form
> > > > to be the denominator? When we specify -A-lnK-S, would the ratio be
> > > > Search1 / Search 2 or Search 2 / Search 1? Do you get Peptide Prophet
> > > > probabilities when you place a static mod on Lys?
> >
> > > > Another interesting point for discussion in methylation: would you be
> > > > able to distinguishdimethylLys from Arginine? Would placing static
> > > > mod ofdimethylon Lys give you many false positives which might be
> > > > just Arginines instead? How do you manage them?
> >
> > > > Bernard
> >
> > > > P.S: Has anybody come across methylated tryptophan W?
> >
> > > > On Mar 11, 10:00 pm, dctrud <[email protected]> wrote:
> >
> > > > > Bernard,
> >
> > > > > We've successfully used ASAPRatio for heavydimethyllabeled
> > > > > quantitation using the following workflow, which might help you get
> to
> > > > > where you want:
> >
> > > > > * Run *two* searches, with the light and heavy methyl n-term and
> > > > > lysine mods specified as *static* modifications, i.e.
> >
> > > > > Search 1:Dimethyl(K) +Dimethyl(n-term) as static mods.
> > > > > Search 2:Dimethyl:2H4 (K) +Dimethyl:2H4 (n-term) as static mods.
> >
> > > > > * Run xinteract on the resulting pair of search results using the
> > > > > static mods option for ASAPRatio, i.e.
> >
> > > > > -A-lnK-S-r0.05
> >
> > > > > There's no need to run XPRESS if you are only interested in
> ASAPRatio
> > > > > results.
> >
> > > > > DT
> >
> > > > > On 11 Mar, 07:05, Bernt <[email protected]> wrote:
> >
> > > > > > Dear all,
> >
> > > > > > I have a question pertaining to ASAPRatio.
> >
> > > > > > Can I actually get ASAPRatio to give me a ratio of Kmethylated /
> Kheavy
> > > > > > +methylated (i.e. K142/K148)? If it can be done, how do I specify
> on
> > > > > > the commandline different modified forms of Lys as the numerator
> and
> > > > > > denominator of the ratio? Both modifications have been specified
> under
> > > > > > variable mods in Xtandem. Does Xpress need to be specified
> everytime
> > > > > > ASAPRatio is run, or can it be omitted? Can the following work?
> >
> > > > > > xinteract  -NinteractHeavyMethyl2.pep.xml -p0 -l6 -OA -A-
> > > > > > lR170.11676K142.11061-F-r0.1-mK148.13061R180.12476
> > > > > > "*HeavyMethyl.tandem.pep.xml"
> >
> > > > > > I also tried specifying static mod on Lys (i.e. 1...@k), and
> variable
> > > > > > mod of 2...@k to represent the Heavy+Methyl form in Xtandem first,
> > > > > > then :
> >
> > > > > > xinteract  -Ninteractstatic.pep.xml -p0 -l6 -OA -X-nR,10K,6
> -A-lRK-F-
> > > > > > r0.1-mK148.13061R180.12476 "*static.tandem.pep.xml"
> >
> > > > > > But in this case, PeptideProphet's probabilities were all 0,
> > > > > > presumably because there were very few significant peptide
> assignments
> > > > > > due to the static mod specified on all Lys. Does anybody have any
> idea
> > > > > > how I can get around this problem with ASAPRatio?
> >
> > > > > > I look forward to any suggestions. Thanks in advance.
> >
> > > > > > Cheers,
> > > > > > Bernard
> >
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