[BioC] From pilot to a large study

[Mark Cowley]

anyone?

I found that the GeneSelector package has some nice stuff for leave-1- 
out (and more) cross validation

mark

On 28/09/2009, at 11:56 AM, Mark Cowley wrote:

> Dear list,
> Rather than reinventing the wheel, I hope someone in the community can
> point me in the right direction.
>
> In a pilot study, we have looked at a single xenograft over time
> (0,8,24,48 hours) with or without drug treatment (7 groups). Using
> Illumina WG6 arrays, with biological quadruplicates and controls at
> each time point we have a phenomenal amount of clean signal at 8hr
> (3200 genes q < 0.05), which tapers off at 24 and 48hr (307 and 65
> genes q < 0.05 respectively).
> This study is about to grow with many more xenograft lines and more
> drugs, so from this pilot study data, we'd like to work out (1) how
> few replicates we can use, yet still get strong signal, and (2)
> whether we need the matched timepoint controls.
>
> part (1) sounds like a leave-one-out cross validation problem, but i'd
> appreciate anyone else's advice here. I've come across the MCREstimate
> package on BioC, and was wondering if there were any others worth  
> using?
> part (2) I can probably assess by comparing DE genes treated vs
> untreated at each timepoint to the values I get comparing treated at
> each timepoint to the time 0 control. It already looks like the
> timepoint controls are very similar to the t0, but there must be a
> more elegant way to quantify this.
>
> Here's where I started re-inventing the wheel:
> by randomly selecting 3 arrays per group, repeating the limma
> analysis, and assessing the number of DE genes that remain, I recover
> ~ 78% of genes with q<0.05, but with just 2 replicates I recover only
> 30% of the genes. I expect that the loss of statistical power, would
> be offset somewhat by the benefits due to moderated t-stats and eBayes
> (since I have 7 groups in the model).
>
> looking for any advice
>
> cheers,
> Mark
>
>
> ----------------------------------------------------------------------
> Mark Cowley, PhD
>
> Peter Wills Bioinformatics Centre
> Garvan Institute of Medical Research
> 384 Victoria St | Darlinghurst | NSW 2010 | Australia
> phone: +61 2 9295 8542 | fax: +61 2 9295 8538 | email: m.cowley at garvan.org.au
>  | web: www.garvan.org.au
> ----------------------------------------------------------------------
>
>
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