[BioC] gains and losses via mode shifting

[Benjamin Otto]

I was hoping there would be a solution, which incorporates some global information about all samples. Suppose I would only have one samples with not so obvious shifting but a segmentation following all others clearly, then I could use this information for the correction. Unfortunately it's not so easy in my case. Yet it naturally makes a difference if my samples group 50 percent to 50 percent according to gain and loss calls versus when they agree on one of the solutions. 

How do I know in that case from a pure bioinformatical point of view that my processing procedures provide reliable results and not some sort of gambling result?

Benjamin


-----Ursprüngliche Nachricht-----
Von: seandavi at gmail.com [mailto:seandavi at gmail.com] Im Auftrag von Sean Davis
Gesendet: Monday, June 30, 2008 1:55 PM
An: Benjamin Otto
Cc: bioconductor at stat.math.ethz.ch
Betreff: Re: [BioC] gains and losses via mode shifting

On Mon, Jun 30, 2008 at 7:02 AM, Benjamin Otto
<b.otto at uke.uni-hamburg.de> wrote:
> Hi,
>
> After the segmentation of CGH data in some papers the results are frequently
> shifted by the density mode. To be more precise the mode of the highest peak
> is used. However this procedure depends on the condition that there is
> clearly one prominent peak dominating the density function.
>
> Currently, in some of my samples, I do have the problem of two prominent
> peaks flanking the y-axis which make the decision about the correct shift
> direction a difficult one. Moreover in some of the cases a shift in one
> direction seems to be obvious, in some other cases a shift in the other
> direction seems more preferable and in a third group the preference is not
> quite clear. But in all groups a segmentation profile in chromosomes 1-3 is
> nearly identical which suggests that I do observe the same gain or loss
> (depending on the shift direction) in all these samples.
>
> Does anyone have an idea how to assess this problem and how to solve it? Is
> there another frequently used procedure aside the density mode shifting used
> for such data?
>
> I do have pictures of some samples displaying the problem but they are too
> big for the mailing list. Is there an official repository I can upload them
> to?

We use the lower of the two modes when there is a "tie".  Since CGH
data is naturally censored at the low end, this makes some sense,
biologically, to do.  However, this is not a perfect solution nor can
there usually be one, as heterogeneity appears to be almost
universally present.  So, there is little chance of determining the
absolute copy number which translates to an inability to absolutely
determine the correct mode.

Sean



-- 
Pflichtangaben gemäß Gesetz über elektronische Handelsregister und Genossenschaftsregister sowie das Unternehmensregister (EHUG):

Universitätsklinikum Hamburg-Eppendorf
Körperschaft des öffentlichen Rechts
Gerichtsstand: Hamburg

Vorstandsmitglieder:
Prof. Dr. Jörg F. Debatin (Vorsitzender)
Dr. Alexander Kirstein
Ricarda Klein
Prof. Dr. Dr. Uwe Koch-Gromus