[BioC] Question about interpretation of CHARM results

[Brent Pedersen]

On Mon, Aug 20, 2012 at 12:28 PM, Tim Triche, Jr. <tim.triche at gmail.com> wrote:
>
>
> On Mon, Aug 20, 2012 at 10:42 AM, Brent Pedersen <bpederse at gmail.com> wrote:
>>
>>
>> > TCGA methylation data is background corrected and dye bias equalized
>> > (for
>> > the 450k samples, at least, and as batches are updated, 27k as well) but
>> > no
>> > batch correction is done for the level 3 data.  In the case of
>> > multi-batch
>> > tumors it is a good idea to run ComBat or (if you must) SVA to
>> > compensate.
>>
>> Sorry to hijack the thread, but, what is the reason to prefer ComBat over
>> SVA?
>
>
> Because in practice, with calibration samples, it seems to work better.
>
>
>> > switching from 0.1% methylated to 99.9% methylated is probably a real
>> > effect.  Switching from 1% to 3% across the board is probably technical
>> > artifacts.
>>
>> I'm guessing this to be true only for tumor/normal comparisons or
>> "pure" samples.
>
>
> Yes, the former typically have distinct cancer-related (vs. tissue-related)
> changes if any, and the latter are a bit like unicorn poop (never seen in
> the wild).
>
> http://www.nature.com/nbt/journal/v30/n5/full/nbt.2203.html?WT.ec_id=NBT-201205#/methods
>
>
>>
>> What about peripheral blood where one may be measuring a signal from a
>> variety of cell types or tissues?
>
>
> Funny you should mention this particular task :-)
>
> http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0041361
>

thanks for this reference, I hadn't seen it. Interesting to read that
after this study:
http://ajrccm.atsjournals.org/content/185/4/373.long
with tiny fold-changes that replicate across populations:
http://ajrccm.atsjournals.org/content/185/4/373/F3.large.jpg


> Given the difficulty of isolating gold standard reference populations by
> flow sorting, it's tough to benchmark the various transformations, but what
> you gain in linearity you may lose in leverage.  Since there isn't one
> particular transformation that simultaneously linearizes and stabilizes a
> proportion,
>
> http://www.jstor.org/discover/10.2307/1269291?uid=2129&uid=2&uid=70&uid=4&sid=21101141681241
>
> you have to pick your battles.  In the case of compositional analysis, 30+
> years after Aitchison and Shen's seminal papers, it appears to remain
> unresolved.   The ability to isolate a small number of highly purified cells
> and perform targeted BS-seq on picogram quantities of DNA may put this to
> rest.
>
> http://leg.est.ufpr.br/lib/exe/fetch.php/pessoais:abtmartins:thestatisticalanalysisofcompositionaldata.pdf
>
> However... joint analysis via DNA methylation and expression (array or
> RNAseq) is another matter, and there I have a candidate (in need of
> validation).
>

I'll keep an eye out for that.
-b

>
> I can't say that I'm entirely unhappy about you 'hijacking' this thread...
>
> --t
>
>