[BioC] Some Genefilter questions

Amy Mikhail a.mikhail at abdn.ac.uk
Thu Nov 30 22:35:47 CET 2006


Hi all,

Jenny, just wanted to clarify what you said; you reckon if I only want to
remove the foreign species probesets I should do this before
preprocessing, but if I want to remove e.g. absent calls from my own
species probes I should do this after preprocessing.  Is this right?

Also, how do I create the character vector of my parasite probesets for
your code?

Robert, I tried subsetting after preprocessing but before analysis ... it
made no difference to the order of probesets, however the numbers changed
slightly (all the probesets had slightly higher adjusted P.values after
removing the parasite probes).  See below:

(a) Toptable for full dataset:

                        ID         M         A          t      P.Value  
adj.P.Val        B
5808   Ag.2R.2004.0_CDS_at -1.870657  9.585064 -16.705963 2.730301e-07
0.006216623 4.207052
12128    Ag.3R.1526.1_a_at -1.129926  9.969329 -13.778759 1.140079e-06
0.010670646 3.731215
6675  Ag.2R.274.0_UTR_a_at -2.967667  9.851482 -13.392310 1.405944e-06
0.010670646 3.650675
6676  Ag.2R.274.1_CDS_a_at -1.871438  9.486805 -12.842425 1.913317e-06
0.010891076 3.526999
7614    Ag.2R.354.0_UTR_at -1.266767  8.481348 -11.394707 4.581189e-06
0.020119389 3.141374
4531    Ag.2L.992.0_CDS_at  2.026152  9.203893  11.167484 5.301785e-06
0.020119389 3.071661
7990  Ag.2R.424.0_CDS_a_at  1.240622  9.747394  10.326106 9.329289e-06
0.030345512 2.787711
7615     Ag.2R.354.16_a_at -2.045494  9.100215 -10.046394 1.135967e-05
0.032331041 2.683414
13171  Ag.3R.2423.0_CDS_at -0.962208  6.088883  -9.672024 1.489835e-05
0.032613809 2.535235
1233     Ag.2L.1092.1_a_at  0.967778 11.195894   9.604850 1.565626e-05
0.032613809 2.507552
3645    Ag.2L.387.0_CDS_at -1.291859  6.257007  -9.596269 1.575616e-05
0.032613809 2.503991
6674  Ag.2R.274.0_CDS_s_at -1.748227  8.217272  -9.022044 2.439458e-05
0.046286683 2.252335

(b) Toptable for dataset minus parasite probesets:

                         ID          M         A          t      P.Value  
adj.P.Val           B
5808    Ag.2R.2004.0_CDS_at -1.8706568  9.585064 -16.460263 4.609906e-07
0.008415383  4.22498712
12128     Ag.3R.1526.1_a_at -1.1299262  9.969329 -13.637285 1.764053e-06
0.013877872  3.73030514
6675   Ag.2R.274.0_UTR_a_at -2.9676671  9.851482 -13.144767 2.289137e-06
0.013877872  3.61989734
6676   Ag.2R.274.1_CDS_a_at -1.8714376  9.486805 -12.626803 3.040892e-06
0.013877872  3.49400490
7614     Ag.2R.354.0_UTR_at -1.2667670  8.481348 -11.227966 6.932125e-06
0.024830944  3.09513993
4531     Ag.2L.992.0_CDS_at  2.0261521  9.203893  10.968142 8.161362e-06
0.024830944  3.01011426
7990   Ag.2R.424.0_CDS_a_at  1.2406222  9.747394  10.167325 1.380828e-05
0.036010013  2.72261326
7615      Ag.2R.354.16_a_at -2.0454939  9.100215  -9.863084 1.702538e-05
0.038169133  2.60232832
13171   Ag.3R.2423.0_CDS_at -0.9622079  6.088883  -9.542971 2.135453e-05
0.038169133  2.46851929
1233      Ag.2L.1092.1_a_at  0.9677780 11.195894   9.475125 2.242393e-05
0.038169133  2.43915802
3645     Ag.2L.387.0_CDS_at -1.2918594  6.257007  -9.440086 2.299975e-05
0.038169133  2.42385347
6674   Ag.2R.274.0_CDS_s_at -1.7482273  8.217272  -8.858858 3.545759e-05
0.053939852  2.15526082

Why would the adjusted P values be higher in the second case (number of
parasite probes removed was about 4,000)?

Regards,
Amy

---------------------------------------------------------------------------

> Hi,
>
> It may be worth pointing out that a related question can have a huge
> impact on normalization of certain glass arrays. One of the standard
> protocols on the Agilent 44K human arrays causes several hundred control
> spots to light up extremely brightly in the green channel, but remain
> completely off in the red channel.  If you leave these control spots in
> the data set when you normalize between channels (i.e., within arrays),
> every known normalization methods breaks -- in the precise sense that it
> will systematically distort the comparison between the red and green
> channels.  If you then model the data incorporating a dye effect, you
> will think that almost every gene exhibits a dye bias.  On the other
> hand, if you remove these control spots before normalizing between
> channels, then modeling the dye bias suggest that it rarely exists....
>
> As for the question originally asked here, I would not expect the
> foreign species probes to break the normalization (unless they somehow
> light up in one group of samples but not in the other). So, my own bias
> would be to keep them for background correction and normalization, but
> remove them before the rest of the analysis.
>
> Best,
> 	Kevin
>
> Jenny Drnevich wrote:
>> Hi Amy,
>>
>> Don't you just love it when you get one response suggesting you do one
>> thing (remove malarial genes after pre-processing) and another response
>> suggesting the opposite?  Although I think in this case Robert was
>> suggesting you remove them after pre-processing because it was easier
>> than
>> trying to modify either the normalization code or the cdf environment,
>> which is what Jim pointed out to you. I ran into this same problem with
>> having probesets for other species on the soybean array, which is why I
>> used Ariel's code. I think that if you're using a mixed species array
>> but
>> only put one of the species on it, then you should remove the other
>> species' probesets BEFORE doing the normalization because they really
>> have
>> no bearing on the transcriptome you're trying to measure. On the other
>> hand, if you also want to filter your species' probesets based on
>> presence/absence, minimum cutoff, variation, etc.* , then you should
>> filter
>> these genes AFTER doing the pre-processing because these probesets do
>> contain information about the transcriptome, even if it is just 'not
>> detectably expressed'.
>>
>> Cheers,
>> Jenny
>>
>> * Contrary to Robert, I prefer to filter on presence/absence (using
>> Affy's
>> calls) rather than variability :) I don't know if there is any
>> documentation on which may be "better"...
>>

-------------------------------------------
Amy Mikhail
Research student
University of Aberdeen
Zoology Building
Tillydrone Avenue
Aberdeen AB24 2TZ
Scotland
Email: a.mikhail at abdn.ac.uk
Phone: 00-44-1224-272880 (lab)
       00-44-1224-273256 (office)



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