FDR and FNR dillemma
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Informatics
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Source: https://stat.ethz.ch/pipermail/bioconductor/2008-December/025556.html
The ball model does not apply to microarray studies. (And the
probability of drawing the red ball in 20 draws is not 1).
But FDR does apply to microarray studies, and so does a less
discussed concept, the false nondiscovery rate or FNR.
Suppose I take 20 independent samples of mouse liver tissue - same
strain, gender ... and hybridize independently to 20 microarrays -
any platform.
Then arbitrarily divide into 2 groups of size 10. If there are
10,000 genes on the array, you should see 1 gene with p-value .0001or
less, 10 genes with p-value .001 or less, 100 genes with p-value .01
or less etc. Now suppose you take the 100 genes with the highest
degree of differential expression and do a PCR study with independent
samples. You should still have 1 gene which is significant with
p=.01 and 5 genes which are significant at p=.05.
The problem is - there is no systematic difference between the
samples. You have detected noise - i.e. chance variation. If you
use the same samples to do your PCR, you may get closer to 100%
"significance" for the selected genes, because the variation that
caused the false detection will still be in the sample unless it was
due only to the hybridization.
FDR is an estimate of the excess of significant findings, compared to
what is expected by chance. You can reduce FDR greatly by doing
independent follow-up studies (on another microarray or on another
platform such as PCR). You cannot reduce FDR much by reusing the
same samples on a different platform, although you will reduce
affects due to technical variation.
However, FDR reduces your power to detect differential
expression. This means that you will have higher FNR if you use
multiple comparisons adjustments. Again, if you do independent
follow-up studies, you can reduce FNR.
The purpose of the FDR computation is to reduce effort wasted on
large gene lists which are mostly reporting noise. But if your
genelist is smaller than you think is reasonable, you may certainly
follow up a larger set of genes and sorting by p-value will give you
the most reasonable set of genes to follow up. Again,
the only valid follow-up uses independent samples and independent platforms. \
--Naomi
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라벨:
Informatics
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