[BioC] Analysis affymetrix of experiment....help please

James W. MacDonald jmacdon at uw.edu
Fri Sep 7 15:55:05 CEST 2012



On 9/7/2012 7:26 AM, Sean Davis wrote:
> On Fri, Sep 7, 2012 at 7:14 AM, suparna mitra<smitra at liverpool.ac.uk>wrote:
>
>> Oh thanks.. I missed this point. But can you suggest me one more thing...
>> when I tried adjust = "BH" (Benjamini-Hochberg I suppose) I got the same
>> result as  adjust = "fdr". for topTable. Is it normal?
>>
> Yes.  They are the same.  See the help for p.adjust for details.
>
>
>> Further when I tried to do vennDiagram I was surprized to see 0 in all
>> circles. Thus I thought I must be doing something wrong. Sorry if my
>> question is silly.
>>
> Unfortunately, you have no significantly differentially-expressed genes.
>   Note that all of the adjusted p-values are pretty high.  You can try to
> filter your genes based on variance before testing to try to reduce the
> number of genes entering your test and multiple correction.  However,
> having worked with this kind of biological system (patients), you may
> suffering from a problem of a small biological effect in the setting of
> large biological variation.  A larger sample size may be necessary.

You may also be suffering from large technical variation, which could be 
helped by applying array weights. See ?arrayWeights for more information.

Best,

Jim

>
> Sean
>
>
>> Here is what I tried.
>>
>>> topTable(fit2.invivo, coef = 1, adjust = "fdr")
>>             ID      logFC   AveExpr         t      P.Value adj.P.Val
>> B
>>
>> 8819  7943047 -0.3640702  4.177681 -5.395110 3.942713e-05 0.3282013
>> -2.023533
>>
>> 9675  7950951 -0.3640702  4.177681 -5.395110 3.942713e-05 0.3282013
>> -2.023533
>>
>> 18889 8043581 -0.3640702  4.177681 -5.395110 3.942713e-05 0.3282013
>> -2.023533
>>
>> 19899 8053785 -0.3640702  4.177681 -5.395110 3.942713e-05 0.3282013
>> -2.023533
>>
>> 3713  7896238  0.7731154  2.999029  4.796490 1.434510e-04 0.9552974
>> -2.323922
>>
>> 19926 8054075 -0.3816217  4.062936 -4.557543 2.424324e-04 0.9998796
>> -2.454618
>>
>> 18660 8041642 -1.0007299  4.220083 -4.290346 4.379518e-04 0.9998796
>> -2.607991
>>
>> 3759  7896284 -0.7555604  5.727302 -4.159251 5.861601e-04 0.9998796
>> -2.685960
>>
>> 6238  7917530  0.5596335 11.170012  4.117421 6.433789e-04 0.9998796
>> -2.711203
>>
>> 15545 8010622 -0.3324189  3.771856 -3.971869 8.899739e-04 0.9998796
>> -2.800385
>>
>>> topTable(fit2.invivo, coef = 2, adjust = "fdr")
>>             ID      logFC   AveExpr         t      P.Value adj.P.Val
>> B
>>
>> 621   7893126 -0.5848178  4.412764 -4.577179 0.0002321630 0.9999684
>> -2.469821
>>
>> 6238  7917530 -0.5783362 11.170012 -4.255023 0.0004737013 0.9999684
>> -2.652426
>>
>> 26642 8120756 -1.0354557  5.439265 -4.238568 0.0004913467 0.9999684
>> -2.662042
>>
>> 1687  7894197 -0.9004303  2.631359 -4.169362 0.0005731153 0.9999684
>> -2.702782
>>
>> 2353  7894871  0.8441561  4.815714  4.161413 0.0005833454 0.9999684
>> -2.707492
>>
>> 3641  7896166 -0.6206262  7.735431 -4.144225 0.0006060986 0.9999684
>> -2.717698
>>
>> 2088  7894602  0.4713716  2.841855  4.115413 0.0006462632 0.9999684
>> -2.734873
>>
>> 5638  7911243 -0.7263053  5.676410 -4.053352 0.0007421075 0.9999684
>> -2.772143
>>
>> 7851  7933619  0.4194965  8.480778  4.040446 0.0007637691 0.9999684
>> -2.779941
>>
>> 20151 8056222 -0.8981049  7.892249 -4.031734 0.0007787485 0.9999684
>> -2.785214
>>
>>> topTable(fit2.invivo, coef = 3, adjust = "fdr")
>>             ID      logFC  AveExpr         t      P.Value adj.P.Val
>> B
>>
>> 2590  7895109 -0.9415442 4.766552 -5.803704 1.670491e-05 0.5562234
>> -0.6982314
>>
>> 6210  7917182 -0.2981341 3.273225 -5.028595 8.656989e-05 0.6545102
>> -1.2472882
>>
>> 27812 8132245 -0.4595908 5.409405 -4.995303 9.304487e-05 0.6545102
>> -1.2727646
>>
>> 867   7893372  1.3251627 3.017891  4.981783 9.581361e-05 0.6545102
>> -1.2831553
>>
>> 26802 8122099 -0.4740894 4.548920 -4.828048 1.338927e-04 0.6545102
>> -1.4031177
>>
>> 808   7893313  1.0125247 7.938503  4.739949 1.623493e-04 0.6545102
>> -1.4733549
>>
>> 26093 8115516 -0.5100673 6.294000 -4.703760 1.757561e-04 0.6545102
>> -1.5025187
>>
>> 587   7893092 -0.9608515 6.013864 -4.631511 2.059886e-04 0.6545102
>> -1.5612836
>>
>> 22913 8084605 -0.3491973 6.211757 -4.519801 2.634837e-04 0.6545102
>> -1.6535466
>>
>> 3828  7896353  0.6239117 4.207636  4.504578 2.724902e-04 0.6545102
>> -1.6662493
>>
>>> results<- decideTests(fit2.invivo)
>>> vennDiagram(results)
>> see the plot attached.
>> Thanks,
>> Mitra
>>
>>
>> On 7 September 2012 12:03, Sean Davis<sdavis2 at mail.nih.gov>  wrote:
>>
>>> On Fri, Sep 7, 2012 at 6:57 AM, suparna mitra<smitra at liverpool.ac.uk
>>>> wrote:
>>>> Dear Sean,
>>>>    I have been reading Bioconductor and limma user guide and thus this
>> is
>>> I
>>>> tried.
>>>> But just being a novice, wanted to make sure if I am right.
>>>> I know I have perform t-test when I created the contrast, but can you
>>>> please help me how can I perform unpaired t-test here. I am concerned
>> as
>>>> the patients in groups are not same.
>>>>
>>>
>>> The t-test you performed was unpaired; unpaired is the "default".
>>>
>>> Sean
>>>
>>>
>>>> Thanks,
>>>> Mitra
>>>>
>>>> On 7 September 2012 11:41, Sean Davis<sdavis2 at mail.nih.gov>  wrote:
>>>>
>>>>>
>>>>> On Fri, Sep 7, 2012 at 5:54 AM, suparna mitra<
>> smitra at liverpool.ac.uk
>>>>> wrote:
>>>>>
>>>>>> Hello Group,
>>>>>> I am trying t analyze my affymetrix (HuGene-1_0-st-v1) data using
>> BiC.
>>>>>> Previously i was using different softwares for this. And this is my
>>>> first
>>>>>> try with Bioconductor for big experiment. So thought to get some
>>> advice
>>>> in
>>>>>> the beginning.
>>>>>> I have Three groups of patient: (In-vivo)
>>>>>>   A-Acute reaction. Patient taking a drug X develops reaction.
>>>>>>   R-recovered (6 weeks after acute reaction-not longer taking drug
>> X).
>>>>>>   T-Tolerant. Patient on X and tolerating treatment.
>>>>>>
>>>>>> Now in in-vitro study we used another constant Y
>>>>>>     RXY recovered and challenged with X+Y
>>>>>>     RY recovered challenged with only Y. RXY vs RY are to exclude
>>> effects
>>>>>> by
>>>>>> Y.
>>>>>>    TXY tolerant and challenged with X+Y,
>>>>>>    TY tolerant challenged with only Y. TXY vs TY are to exclude
>> effects
>>>> by
>>>>>> Y.
>>>>>>
>>>>>> No I want to check the cross relation and effects A vs R, RvsT and
>>> Avs T
>>>>>> and  differentially expressed genes for each comparison. And the
>> same
>>> in
>>>>>> invitro. There are not same patients in different groups, thus I
>>> think I
>>>>>> want to apply unpaired-t test.
>>>>>>
>>>>>> This is what I tried:
>>>>>>> sessionInfo()
>>>>>> R version 2.15.1 (2012-06-22)
>>>>>> Platform: i386-apple-darwin9.8.0/i386 (32-bit)
>>>>>>
>>>>>> locale:
>>>>>> [1] en_GB.UTF-8/en_GB.UTF-8/en_GB.UTF-8/C/en_GB.UTF-8/en_GB.UTF-8
>>>>>>
>>>>>> attached base packages:
>>>>>> [1] stats     graphics  grDevices utils     datasets  methods   base
>>>>>>
>>>>>> other attached packages:
>>>>>>   [1] statmod_1.4.15              limma_3.12.1
>>>>>>   annotate_1.34.1             hugene10stprobeset.db_8.0.1
>>>>>> org.Hs.eg.db_2.7.1
>>>>>>
>>>>>>   [6] BiocInstaller_1.4.7         affycoretools_1.28.0
>>>>   KEGG.db_2.7.1
>>>>>>                GO.db_2.7.1                 AnnotationDbi_1.18.1
>>>>>> [11] affy_1.34.0                 Biobase_2.16.0
>>>>>>   BiocGenerics_0.2.0          pd.hugene.1.0.st.v1_3.6.0
>>> RSQLite_0.11.1
>>>>>> [16] DBI_0.2-5                   oligo_1.20.4
>>>>>>   oligoClasses_1.18.0
>>>>>>
>>>>>>
>>>>>>   rmaOligoinvivo = oligo::rma(InVivodat1)
>>>>>> Background correcting
>>>>>> Normalizing
>>>>>> Calculating Expression
>>>>>>
>>>>>>> rmaOligoinvitro = oligo::rma(InVitrodat1)
>>>>>> Background correcting
>>>>>> Normalizing
>>>>>> Calculating Expression
>>>>>>
>>>>>>> maplot(rmaOligoinvivo)
>>>>>>> maplot(rmaOligoinvitro)
>>>>>>> InVivoTargets
>>>>>>   FileName Treatment
>>>>>> 1   MC1       A
>>>>>> 2   MC2       A
>>>>>> 3   MC3       A
>>>>>> 4   MC4       A
>>>>>> 5   MC5       A
>>>>>> 6   MC6       A
>>>>>> 7   MC7       R
>>>>>> 8   MC8        R
>>>>>> 9   MC9        R
>>>>>> 10 MC10        R
>>>>>> 11 MC11        R
>>>>>> 12 MC12        R
>>>>>> 13 MC13       T
>>>>>> 14 MC14        T
>>>>>> 15 MC15        T
>>>>>> 16 MC16        T
>>>>>> 17 MC17        T
>>>>>> 18 MC18        T
>>>>>>
>> InVitroTargets=readTargets("~/Desktop/Recent/Liverpool-work-related/Micro_RawData/InVitroTargets.txt")
>>>>>>> InVitroTargets
>>>>>>     FileName Treatment Batch  CD4
>>>>>> 1  MC19       RY     1 High
>>>>>> 2  MC20        TY     1  Low
>>>>>> 3  MC21        RY     2 High
>>>>>> 4  MC22        TY     2 High
>>>>>> 5  MC23        TY     2  Low
>>>>>> 6  MC24        RY     2 High
>>>>>> 7  MC25        TXY     1  Low
>>>>>> 8  MC26       RXY     1 High
>>>>>> 9  MC27       RXY    2  Low
>>>>>> 10 MC28        TXY    2 High
>>>>>> 11 MC29        RXY     2 High
>>>>>> 12 MC30      TXY    2 High
>>>>>>
>>>>>> f.invivo<- factor(InVivoTargets$Treatment, levels = c("A", "R",
>> "T"))
>>>>>> design.invivo<- model.matrix(~0 + f.invivo)
>>>>>>
>>>>>>> colnames(design.invivo)<- c("A", "R", "T")
>>>>>>> fit.invivo<- lmFit(rmaOligoinvivo, design.invivo)
>>>>>>> contrast.matrix.invivo<- makeContrasts(R-A, T-R, T-A,levels =
>>>>>> design.invivo)
>>>>>>
>>>>>>> fit2.invivo<- contrasts.fit(fit.invivo, contrast.matrix.invivo)
>>>>>>> fit2.invivo<-eBayes(fit2.invivo)
>>>>>>> topTable(fit2.invivo, coef = 1, adjust = "fdr")
>>>>>>             ID      logFC   AveExpr         t      P.Value adj.P.Val
>>>>>> B
>>>>>>
>>>>>> 8819  7943047 -0.3640702  4.177681 -5.395110 3.942713e-05 0.3282013
>>>>>> -2.023533
>>>>>>
>>>>>> 9675  7950951 -0.3640702  4.177681 -5.395110 3.942713e-05 0.3282013
>>>>>> -2.023533
>>>>>>
>>>>>> 18889 8043581 -0.3640702  4.177681 -5.395110 3.942713e-05 0.3282013
>>>>>> -2.023533
>>>>>>
>>>>>> 19899 8053785 -0.3640702  4.177681 -5.395110 3.942713e-05 0.3282013
>>>>>> -2.023533
>>>>>>
>>>>>> 3713  7896238  0.7731154  2.999029  4.796490 1.434510e-04 0.9552974
>>>>>> -2.323922
>>>>>>
>>>>>> 19926 8054075 -0.3816217  4.062936 -4.557543 2.424324e-04 0.9998796
>>>>>> -2.454618
>>>>>>
>>>>>> 18660 8041642 -1.0007299  4.220083 -4.290346 4.379518e-04 0.9998796
>>>>>> -2.607991
>>>>>>
>>>>>> 3759  7896284 -0.7555604  5.727302 -4.159251 5.861601e-04 0.9998796
>>>>>> -2.685960
>>>>>>
>>>>>> 6238  7917530  0.5596335 11.170012  4.117421 6.433789e-04 0.9998796
>>>>>> -2.711203
>>>>>>
>>>>>> 15545 8010622 -0.3324189  3.771856 -3.971869 8.899739e-04 0.9998796
>>>>>> -2.800385
>>>>>> I am progressing in a right way? Further I want to perform unpaired
>> t
>>>> test
>>>>>> for comparing AvsT and so on. Any help will be really great.
>>>>>>
>>>>> Hi, Mitra.  I think that looks about right.  You have already
>> performed
>>>>> the unpaired t-test of AvsT (well, actually TvsA, but the p-values
>> will
>>>> be
>>>>> the same) as coefficient 3.
>>>>>
>>>>> Sean
>>>>>
>>>>>
>>>>
>>>>
>>>> --
>>>> Dr. Suparna Mitra
>>>> Wolfson Centre for Personalised Medicine
>>>> Department of Molecular and Clinical Pharmacology
>>>> Institute of Translational Medicine University of Liverpool
>>>> Block A: Waterhouse Buildings,  L69 3GL Liverpool
>>>>
>>>> Tel.  +44 (0)151 795 5394, Internal ext: 55394
>>>> M: +44 (0) 7511387895
>>>> Email id: smitra at liverpool.ac.uk
>>>> Alternative Email id: suparna.mitra.sm at gmail.com
>>>>
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>>>>
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>>>>
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>>>
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>>
>>
>> --
>> Dr. Suparna Mitra
>> Wolfson Centre for Personalised Medicine
>> Department of Molecular and Clinical Pharmacology
>> Institute of Translational Medicine University of Liverpool
>> Block A: Waterhouse Buildings,  L69 3GL Liverpool
>>
>> Tel.  +44 (0)151 795 5394, Internal ext: 55394
>> M: +44 (0) 7511387895
>> Email id: smitra at liverpool.ac.uk
>> Alternative Email id: suparna.mitra.sm at gmail.com
>>
>> _______________________________________________
>> Bioconductor mailing list
>> Bioconductor at r-project.org
>> https://stat.ethz.ch/mailman/listinfo/bioconductor
>> Search the archives:
>> http://news.gmane.org/gmane.science.biology.informatics.conductor
>>
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-- 
James W. MacDonald, M.S.
Biostatistician
University of Washington
Environmental and Occupational Health Sciences
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Seattle WA 98105-6099



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