To add to the list of references, see also:

Yamamoto, G.; Nannya, Y.; Kato, M.; Sanada, M.; Levine, R. L.;
Kawamata, N.; Hangaishi, A.; Kurokawa, M.; Chiba, S.; Gilliland, D.
G.; Koeffler, H. P. & Ogawa, S. Highly sensitive method for genomewide
detection of allelic composition in nonpaired, primary tumor specimens
by use of affymetrix single-nucleotide-polymorphism genotyping
microarrays. Am J Hum Genet, 2007, 81, 114-126 PMID: 17564968.

/Henrik

On Fri, Jun 26, 2009 at 10:29 AM, Lavinia<lavinia.gor...@mcri.edu.au> wrote:
>
> Thanks for your email Henrik.
>
>> When you say heterogeneous, do you mean that they contain a lot of CN
>> aberrations or do you mean that they have different noise levels?
>
> Different noise levels.
>
>>
>> If "not too many" things go on in your reference samples, then you
>> should expect to get an improvement when you calculate the reference
>> channel as the average over a larger and larger pool of samples.  A
>> few years ago I checked this on 500K data and I found a dramatic drop
>> in SNRs when increasing from 5 to 10 to 20 reference samples and then
>> i flattened out.
>>
>> However, if you look Nannya et al (2005), their CNAG method tries to
>> identify a subset of reference samples that gives best SNRs.  This is
>> to say that you believe there is a set of reference samples that are
>> more "normal" than others.  An alternative argument, which may make
>> even more sense is that there will always be some systematic effects
>> remaining in the estimates and if you can locate a set of reference
>> samples that have similar remaining effects as you test sample, they
>> will cancel out better than if other reference samples where used.
>> Note that this strategy uses different pools of references for each
>> test sample.   I know that the Broad Institute (Gaddy Getz, Scott
>> Carter et al.) are doing something similar in the TCGA project and
>> they say they get better SNRs.
>
> thank you very much for these pointers, I'll look into them.
> I'll try and do something a bit more systematic and post the results.
>
> cheers
>
> Lavinia.
> >
>

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