[BioC] what's really in hgu133plus2.db?

[James W. MacDonald]

Hi David,

On 2/18/2011 2:58 PM, David Iles wrote:
> Jim,
>
> Thanks for your response. The point of understanding exactly where a
> probeset is located is of fundamental importance because it is now
> clear from the ENCODE project that around 90% of genome sequence is
> actively transcribed in a regulated way - John Mattick presented an
> excellent talk introducing this topic at the HGM2007 meeting in
> Montreal. The question then is; 'is it mRNA or another (regulatory?)
> RNA species that we are measuring?'. The fact that 'orphaned'
> probesets detect significantly up- or down-regulated transcription is
> extremely interesting and should not be ignored just because they now
> map outside 'genes' (whatever they may be - the human GNAS locus
> generates 59 different transcripts, some of which do not overlap).

Which is the gist of my original question to you. The annotation 
packages we provide take the original manufacturer at their word and 
simply map the intended target to other annotation sources. Therefore, 
if you are interested in 'non-traditional' (for lack of a better term) 
transcripts, then the updated status of the annotation databases isn't 
relevant.

However, the packages that have been developed for next-gen sequencing 
may be of interest. The Biostrings and BSGenome.Hsapiens.UCSC.hgXX 
packages will allow you to very quickly align all the probesets to the 
genome of your choice. Then depending on how you want to proceed, things 
like rtracklayer, GenomicFeatures, GenomicRanges, etc can help discern 
known transcripts from possible 'other' RNA species.

Best,

Jim


>
> Dave Dr David Iles Institute for Integrative and Comparative Biology
> University of Leeds Leeds LS2 9JT
>
> d.e.iles at leeds.ac.uk
>
>
>
>
> On 18 Feb 2011, at 19:24, James W. MacDonald wrote:
>
>> Hi David,
>>
>> On 2/18/2011 11:41 AM, David Iles wrote:
>>> Dear All,
>>>
>>> Can anyone point me to a URL where I can obtain an overview of
>>> the sources of the data incorporated in the current version of
>>> hgu133plus2.db? I saw to my horror that the actual probesets are
>>> based on a really obsolete human genome assembly (2003), which
>>> has changed significantly over the years. As have also genes,
>>> gene locations, genomic intervals, RefSeq/UniGene entries
>>> etcetcetc......
>>
>> So what exactly is the question? As you note, the chip was designed
>> in the early 2000's, so was necessarily based on a (now) old
>> version of the UniGene database. That is the downfall of the
>> expression arrays; they are stale almost from the instant they hit
>> the market.
>>
>> Since the probesets are based on things that may now be different,
>> it is to a certain extent irrelevant how current the hgu133plus2.db
>> data are, because the probeset -->  gene mappings may be suspect.
>> You can update the gene info all you want, but if the probeset
>> doesn't actually measure a given transcript, then what is the
>> point?
>>
>> We base the annotation on the probeset -->  entrez gene mappings
>> supplied by Affymetrix, which are supposed to be updated regularly.
>> Not having checked that (and given the fact that we take no stance
>> on the veracity of these mappings), they are what they are. Any
>> significant results will require close inspection of the probesets
>> to determine if you believe that they measure what they purport to
>> measure.
>>
>> As an alternative, you can try the MBNI re-mapped probesets, which
>> both update the mappings and remove replicate probesets (by
>> creating single probesets per gene/transcript/etc). They can be
>> obtained via biocLite, or individually here:
>>
>> http://brainarray.mbni.med.umich.edu/Brainarray/Database/CustomCDF/CDF_download.asp
>>
>>
>>
Best,
>>
>> Jim
>>
>>
>>>
>>> Thanks
>>>
>>> Dave Dr David Iles Institute for Integrative and Comparative
>>> Biology University of Leeds Leeds LS2 9JT
>>>
>>> d.e.iles at leeds.ac.uk
>>>
>>> _______________________________________________ Bioconductor
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>>
>>
>>>
-- 
>> James W. MacDonald, M.S. Biostatistician Douglas Lab University of
>> Michigan Department of Human Genetics 5912 Buhl 1241 E. Catherine
>> St. Ann Arbor MI 48109-5618 734-615-7826
>> **********************************************************
>> Electronic Mail is not secure, may not be read every day, and
>> should not be used for urgent or sensitive issues
>>
>
> _______________________________________________ Bioconductor mailing
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-- 
James W. MacDonald, M.S.
Biostatistician
Douglas Lab
University of Michigan
Department of Human Genetics
5912 Buhl
1241 E. Catherine St.
Ann Arbor MI 48109-5618
734-615-7826
**********************************************************
Electronic Mail is not secure, may not be read every day, and should not be used for urgent or sensitive issues