[BioC] Re: Logit-t vs RMA

Gordon Smyth smyth at wehi.edu.au
Sat Sep 27 15:45:50 MEST 2003

At 02:54 AM 27/09/2003, Jenny Drnevich wrote:
> >> My enthusiasm regarding the paper is that it is the first one (to my
> >> knowledge) that has interrogated probe_set differences at the probe
> >> level  across groups (rather than pairwise),

This is what Ben Bolstad's AffyExtensions package does.

>I haven't had a chance to read this paper yet, but I am looking forward to
>However, have you seen: Chu, Weir, & Wolfinger.  A systematic statistical
>linear modeling approach to oligonucleotide array experiments MATH BIOSCI
>176 (1): 35-51 Sp. Iss. SI MAR 2002
>They advocate using the probe-level data in a linear mixed model.
>Assuming that each probe is an independent measure (which I know is not
>true because many of them overlap, but I'm ignoring this for now), using
>probe-level data gives 14-20 "replicates" per chip. We've based our
>analysis methods on this, and with two biological replicates per genetic
>line, and three genetic lines per phenotypic group, we've been able to
>detect as little as a 15% difference in gene expression at p=0.0001 (we
>only expect 2 FP and get 60 genes with p=0.0001).

Mmmm. Getting very low p-values from just two biological replicates doesn't 
lead you to question the validity of the p-values?? :)


>  Should have the
>manuscript submitted in a couple weeks, and I'm working on using our
>method on the benchmark data to see how it compares.  Results to be
>especially since the
> >> authors reported  what I suspected- that the probe level data does a
> >> better job than the  expression values generated by a probe level
> >> algorithm (I could still be  totally wrong, but it IS what I have been
> >> suspecting). This may be more  important for discerning meaningful
> >> differences than the transforms  themselves. If it is possible to
> >> interrogate the data at this level, why  bother with probe level
> >> algorithms which may lose information in the  process of cooking 11-32
> >> intensity values into a single number?
>Jenny Drnevich, Ph.D.
>Department of Animal Biology
>University of Illinois, Urbana-Champaign
>515 Morrill Hall
>505 S. Goodwin Ave.
>Urbana, IL 61801
>ph: 217-244-6826
>fax: 217-244-4565
>drnevich at uiuc.edu

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