[BioC] Identifying Processes as Upregulated or Downregulated

[James W. MacDonald]

Hi Joseph,

I think you are making a simplifying assumption that isn't helpful. In 
other words, you are assuming that up-regulation of a set of genes 
means something different than down-regulation, or a mixture thereof. 
But this flies in the face of much that we know about biological 
processes.

As an example, say we have a set of genes with 'programmed cell death' 
as their GO term. And further assume that some of these genes enhance 
this process, and some prevent the process. Now if most of the 
enhancers are up-regulated, and most of the 'preventers' are 
down-regulated, are you prepared to say these genes should be tested 
separately because the up-regulated genes are involved with a different 
process than the down-regulated genes?

Best,

Jim



On Monday, February 10, 2014 6:43:52 PM, Joseph Shaw wrote:
> Hi all,
>
> I am in the process of performing some ontological analysis with
> GOstats. Given that GOstats doesn't require any information on
> relative increases or decreases in expression for its hypergeometric
> testing procedure, am I correct in assuming that it does not
> differentiate between upregulated and downregulated genes?
>
> If this is the case then providing a list of differentially expressed
> genes (both upregulated and downregulated) to the testing procedure
> will result in ontology results where upregulation and downregulation
> may be confounded.
> In other words, combining upregulated and downregulated genes and
> comparing the resulting list to the gene universe will enable the
> testing procedure to identify regulated ontological processes, but it
> won't be able to identify whether the processes are upregulated or
> downregulated. In fact, given that there is no distinction provided as
> input, it may even be both.
>
> To me, it seems that in order to prevent this from happening two
> separate testing procedures should be performed: one comparing
> upregulated genes to the gene universe and one comparing downregulated
> genes to the gene universe. Is this approach advisable? Is there a
> correct protocol which addresses the above issue?
>
> Joseph
>
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--
James W. MacDonald, M.S.
Biostatistician
University of Washington
Environmental and Occupational Health Sciences
4225 Roosevelt Way NE, # 100
Seattle WA 98105-6099