[BioC] hyperG over chromosome position...?

[Robert Gentleman]

Dario Greco wrote:
> hi all,
> thanks a lot for your emails and for implementing something (too late, 
> you kind of promised now)! :)
> i will not even try, as i am far away from being a proper developer, i 
> guess :)
> 
> I agree that in many cases the chromosomal location is not biologically 
> relevant, but there are some situations where it might be interesting to 
> investigate.
> 
> i am right now working with two different datasets:
> 1) a dataset where the subject is Down Syndrome. of course it could 
> sound stupid, but still nice to provide statistics for the massive chr21 
> upregulation :)

  umm, if you look at the figure on p 179 of our monograph, you will see 
that there is no such massive up-regulation (at least for the data 
presented there). A blunt instrument is unlikely to detect the sorts of 
changes (at least on a single sample basis) that might be of interest.

> moreover, there are interesting issues of "critical regions" for 
> diseases that are associated to DS and that have been historically 
> described in certain cytobands of chr21 (eg. AtrioVentricular Septal 
> Defect - AVSD - having probably 21q2.3 as critical region) .
> 2) a dataset where the subject is Tybe 2 Diabetes where i apparently 
> observe clusters of dis-regulated genes located into the same 
> chromosomal regions.
> 
> besides these autobiographic stories, there are appealing theories 
> inferring  that co-regulated genes might sit (sometimes) close to each 
> other onto the same chromosomal region, to my understanding.


   yes, and hopefully the facts will coincide - as I said there are 
certainly some biological reasons for this sort of behavior, in some 
diseases. Fishing expeditions are IMHO unlikely to be useful.

> 
> i anyway agree with the fact that cytobands don't represent a very 
> meaningful way to define chromatin "spots", but they are quite easy to 
> deal with. definitely it would be much better to have something more 
> "biological" to split the chromosomes!
> 
> thanks again for your attention and help!
> sincerely
> d
> 
> -- 
> Dario Greco
> 
> Institute of Biotechnology - University of Helsinki
> Building Cultivator II
> P.O.Box 56    Viikinkaari 4
> FIN-00014    Finland
> 
> Office: +358 9 191 58951
> Fax: +358 9 191 58952
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> 
> Lab WebPage:
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> 
> Personal WebPage:
> http://www.biocenter.helsinki.fi/bi/dna-microarray/dario.htm
> 
> -- 
> Dario Greco
> 
> Institute of Biotechnology - University of Helsinki
> Building Cultivator II
> P.O.Box 56    Viikinkaari 4
> FIN-00014    Finland
> 
> Office: +358 9 191 58951
> Fax: +358 9 191 58952
> Mobile: +358 44 023 5780
> 
> Lab WebPage:
> http://www.biocenter.helsinki.fi/bi/dna-microarray/
> 
> Personal WebPage:
> http://www.biocenter.helsinki.fi/bi/dna-microarray/dario.htm
> 
> 
> 
> On Jan 16, 2007, at 8:29 PM, Robert Gentleman wrote:
> 
>> Hi,
>>   Just a couple of notes,
>> 1) chromosomal location is typically not biologically relevant in 
>> higher organisms, AFAIK. Since I work at a cancer center, and since 
>> some (but by no means all) genomic abnormalities in cancer induce an 
>> effect that can be detected by chromosomal location these sorts of 
>> things are interesting to me. Anyone using this approach should, IMHO, 
>> have a sound biological reason for doing so.
>>
>> 2) Chromosome bands are probably not ideal (as Francois so correctly 
>> points out), but they have the advantage of being easily obtained. 
>> Other options will require more effort.
>>
>> 3) the code that does this in the Category package and is called 
>> MAPAmat, but it is flawed in a number of ways. Seth and I will put 
>> something up that is better in a week or two.
>>
>> 4) any other contributions are welcome, particularly well implemented 
>> and documented functions.
>>
>>  best wishes
>>    Robert
>>
>> Francois Pepin wrote:
>>> Hi Dario,
>>> It is possible to do it with the chromosomal band using Category. That
>>> was the last part of Robert Gentleman's Category tutorial at BioC2006
>>> (http://www.bioconductor.org/workshops/2006/BioC2006/labs/rgentleman/).
>>> I'm not convinced if the chromosomal bands are the best partition to use
>>> in that case, but it's a good starting point.
>>> Francois
>>> On Tue, 2007-01-16 at 07:43 -0800, Seth Falcon wrote:
>>>> Hi Dario,
>>>>
>>>>>> Dario Greco wrote:
>>>>>>> hi all,
>>>>>>> i would like to perform hyperGTest using the chromosome 
>>>>>>> position   (stored usually in pkgMAP environment).
>>>>>>> how could it be possible?
>>>> Actually, this is on my list of things to add to the Category
>>>> package.  If you, or anyone, wants to do some programming, take a look
>>>> at how the KEGG and PFAM tests are implemented.  A first pass for
>>>> chromosome position will be quite similar.
>>>>
>>>> + seth
>>>>
>>>> -- 
>>>> Seth Falcon | Computational Biology | Fred Hutchinson Cancer 
>>>> Research Center
>>>> http://bioconductor.org
>>>>
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>>
>> --Robert Gentleman, PhD
>> Program in Computational Biology
>> Division of Public Health Sciences
>> Fred Hutchinson Cancer Research Center
>> 1100 Fairview Ave. N, M2-B876
>> PO Box 19024
>> Seattle, Washington 98109-1024
>> 206-667-7700
>> rgentlem at fhcrc.org
> 
> 

-- 
Robert Gentleman, PhD
Program in Computational Biology
Division of Public Health Sciences
Fred Hutchinson Cancer Research Center
1100 Fairview Ave. N, M2-B876
PO Box 19024
Seattle, Washington 98109-1024
206-667-7700
rgentlem at fhcrc.org