Hi.
On Thu, Jan 27, 2011 at 11:03 PM, Gregory W <greg.d.w...@gmail.com> wrote:
> Hello,
>
> I was hoping to get some insight as to whether using a pooled
> reference or paired normal is more appropriate when performing cbs.
>
> I could see how using a paired tumor normal approach could be
> beneficial, say, by negating benign CNVs in the individuals germline.
> I believe these germline CNVs would have a better chance of being
> reported significant when using a pooled reference.
>
> However, I could also see how germline CNVs that may be indicative of
> a predisposition to the tumor would be eliminated when using the
> paired tumor normal paradigm.
>
> Are there other factors I should be taking into account? Let's say
> all my samples were performed from the same institution. Any
> suggestions of how to compare which result is "better"?
I would say it depends what you are looking for. If you are
interested in the difference between a tumor and a match germline
("normal"), then you want to do a paired analysis. If you worry about
the germline not being "normal" (i.e. diploid) everywhere, then you
may also need to look at the normal relative to an "external global"
reference (e.g. a very large pool of normals). Looking only at the
tumor relative to an external global reference will never let you know
whether a CN aberration observed in the tumor is somatic or in the
germline. Thus, I'd say collection paired tumor normal data is always
useful.
Ideally, we'll one day have a CN segmentation and CN calling algorithm
that operates on (tumor, normal, global reference) and provides
easy-to-interpret results.
>
> Thank you in advance,
>
> Greg
>
> P.S. Did TCGA use a pooled reference when finding aberrant regions?
Sorry, I've been a little bit out of the TCGA loop recently, so take
my comment on this with a grain of salt; A while ago when the ovarian
(OV) analysis was mainly done on paired CN ratios. This was basically
due to lack of resources/time, but the above issues were definitely
discussed.
Hope this helps
/Henrik
>
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