[BioC] segmentation aCGH data

jhs1jjm at leeds.ac.uk jhs1jjm at leeds.ac.uk
Wed Oct 10 17:04:33 CEST 2007


Hi Ramon,

Ah, of course, I'd forgotten I'd performed that step. I'm still getting
some segments with high means corresponding to single genes but this'll
be because they are represented by more than 1 probe I guess. The
DNAcopy document has a step in it to remove local trends in the data.
I'm undoing splits that are not at least 3 SDs apart as set out in the
document.

To summarize then,I might use DNA copy to identify regions but in order
to look at single probe aberrations I'd want to use one of the other
methods i.e HMM

Thanks
John

Quoting Ramon Diaz-Uriarte <rdiaz at cnio.es> on Wed 10 Oct 2007 15:22:22
BST:

> Dear John,
>
> On Wednesday 10 October 2007 15:52, jhs1jjm at leeds.ac.uk wrote:
> > Hi list,
> >
> > I've been looking at 3*44k and 2*244k agilent CGH arrays. To date
> I've
> > used limma to read in the processed signals (no background
> correction
> > or normalization as this has been done), then the DNAcopy package
> for
> > segmentation as well as the snapCGH package to employ other
> > segmentation methods rather than use each segmentation package
> > individually.
> >
> > Firstly using the DNAcopy segmentation I can see a significant
> pattern
> > across my 3*44k arrays which disappears when I perform the step to
> > remove unnecessary change points due to trends in the data. As
> these
>
> How exactly are you removing "unnecesary change points due to trends
> in the
> data"?
>
>
> > are in the same locations across the 3 arrays then is it likely
> that
> > this is biologically significant rather than being a trend?
> Obviously
> > others do not have a definitive answer for this but I wondered if
> > anyone had seen similar results in a different scenario.
> >
> > Additionally I'm wondering what segmentation methods people have
> tended
> > to employ. The heterogeneous nature of my data means that I need to
> > identify  single probe as well as larger region aberrations and I'd
> > read that the CBS algorithm is not particular suited to doing this?
>
> If you run the "smooth.CNA" function (in the DNAcopy package), as it
> is
> recommended in the documentation for DNAcopy (IIRC), then single
> probe
> aberrations are not detectable (you are smoothing them away).
>
> Single probe aberrations might be detected with the HMM model in
> snapCGH or
> our HMM model in RJaCGH, available from CRAN
> (http://cran.r-project.org/src/contrib/Descriptions/RJaCGH.html).
> (Details of
> the method available from the paper:
>
http://compbiol.plosjournals.org/perlserv/?request=get-document&doi=10.1371%2Fjournal.pcbi.0030122).
>
>
> Best,
>
> R.
>
>
> > Apologies   if this is a bit vague.
> >
> > Thanks for any input,
> >
> > John
> >
> > _______________________________________________
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>
> --
> Ramón Díaz-Uriarte
> Statistical Computing Team
> Centro Nacional de Investigaciones Oncológicas (CNIO)
> (Spanish National Cancer Center)
> Melchor Fernández Almagro, 3
> 28029 Madrid (Spain)
> Fax: +-34-91-224-6972
> Phone: +-34-91-224-6900
>
> http://ligarto.org/rdiaz
> PGP KeyID: 0xE89B3462
> (http://ligarto.org/rdiaz/0xE89B3462.asc)
>
>
>
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