Perhaps Dr. Smyth is referring to the uncorrected Type I inflation that can
be introduced by correlation within gene sets, and which seems to remain
uncorrected in typical gene set analyses?  Di Wu wrote a nice paper on
this, centered on the 'camera' function, which indicated that severe type I
inflation could be reined in by empirically correcting for the correlation
within sets.

http://nar.oxfordjournals.org/content/40/17/e133

I am not an expert but I found the paper interesting, moreso in light of
papers from Rick Young's lab at the Whitehead Institute which, in so many
words, suggest that widespread transcription amplification by (e.g.) c-Myc
may render many assumptions underlying quantile normalization invalid.  It
would seem that many assumptions from microarray analysis are due for
re-examination if my observations are not far off base.  But, I am not an
expert and would love to hear from those who are.



On Sun, Dec 2, 2012 at 2:41 AM, Steve Lianoglou <
mailinglist.honeypot@gmail.com> wrote:

> Hi Gordon,
>
> When an expert comments on a topic I'm interested in, it's hard for me
> not to press for more insight so I hope you don't mind, but also ...
> you know .. take your time :-)
>
> On Sat, Dec 1, 2012 at 8:39 PM, Gordon K Smyth <smyth@wehi.edu.au> wrote:
> [snip]
> > The term "gene set enrichment analysis" was coined by the Broad
> Institute:
> >
> >   http://www.broadinstitute.org/gsea/
> >
> > but you certainly can't simply give a list of genes to GSEA.  It requires
> > complete data and is designed for microarrays rather than RNA-Seq anyway.
>
> I'm curious if you say so because GSEA doesn't account for something
> like length bias? The GSEA folks seem to suggest that one could do
> this like any other "pre-processed" GSEA analysis by simply providing
> a ranked list of genes (presumably by fold-change):
>
>
> http://www.broadinstitute.org/cancer/software/gsea/wiki/index.php/FAQ#Can_I_use_GSEA_to_analyze_SNP.2C_SAGE.2C_ChIP-Seq_or_RNA-Seq_data.3F
>
> Would you mind (briefly) elaborating a bit on why you disagree?
>
> Thanks,
> -steve
>
> --
> Steve Lianoglou
> Graduate Student: Computational Systems Biology
>  | Memorial Sloan-Kettering Cancer Center
>  | Weill Medical College of Cornell University
> Contact Info: http://cbio.mskcc.org/~lianos/contact
>
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-- 
*A model is a lie that helps you see the truth.*
*
*
Howard Skipper<http://cancerres.aacrjournals.org/content/31/9/1173.full.pdf>

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