[BioC] two pair dye-swap (replicates) conducted in different labs

kevin Lin khlin at odin.mdacc.tmc.edu
Mon Sep 19 22:39:04 CEST 2005


Dear BioC,

I have technical replicates are in dye-swap pairs with four hybs 
conducted in house and four hybs conducted in commercial lab. Same 
RNA samples were used.

Please see belows, I did separated analyses using Limma pipeline 
commands. My Qs is

1)  For IN HOUSE analysis, the corfit$consensus is supposed to be a 
negative number according to limma usersguide (the technical 
replicates are dye-swap and should vary in opposite directions). Why 
am I getting a positive number in the dye-swap design? Is there 
something wrong with my design matrix or I misunderstood points in 
the usersguide?

2) The result from IN HOUSE data seems to be nice, there are some DE 
genes in the listing. Instead, there is nothing differencially 
expressed genes for the data from OS LAB. So is it POSSIBLE? 
Assuming it is possible 'cause variations  which came from operations 
from different lab, what should I do from now on?

3) What do I expect to get if I pull those 8 arrays ( yet, I have not 
done it)  and do the analysis together? Even though, two results have 
so much difference in separate analyses (if all this based on correct 
analysis).

I am confused.

I appreciate if anyone could point me out.

Kevin

***** commands and outputs below ******

#####################################################################
## IN HOUSE: Two pairs of dye-swap experiments conducted in FG
## 1st, 2nd and 3rd, 4th are dye-swap pairs.
#####################################################################
library(limma)
TargetsGenePix <- readTargets("FGtargets.txt")

>  TargetsGenePix

                                     SlideNumber    FileName 
Cy3                 Cy5
FG WT rep1 Sep2005    3215L              FG WT rep1 Sep2005.gpr  WT 
control      WT UV
FG WT rep2 Sep2005    3202OL           FG WT rep2 Sep2005.gpr   WT UV 
WT control
FG KO rep2 Sep2005    3215OL            FG KO rep2 Sep2005.gpr   KO 
control      KO UV
FG KO rep1 Sep2005    3202L              FG KO rep1 Sep2005.gpr   KO 
UV            KO control

SpotTypes <- readSpotTypes()
RGgpr <- read.maimages(TargetsGenePix$FileName, 
source="genepix",wt.fun=wtflags(w=0),annotation=c("Block","Row","Column","Name", 
"controltype"))
RGgpr$printer <- getLayout(RGgpr$genes)
RGgpr$genes$Status <- controlStatus(SpotTypes, RGgpr$genes)
MAgpr <- normalizeWithinArrays(RGgpr,method="loess")
design <- c(1,-1,1,-1)
corfit <- duplicateCorrelation(MAgpr, design, ndups=1, block=c(1,1,2,2))

## > corfit$consensus
## [1] 0.3108369

fit <- lmFit(MAgpr, design, block=c(1,1,2,2), correlation=corfit$consensus)
fit <- eBayes(fit)
top200 <- topTable(fit,n=200,adjust="fdr")

       Block Row Column    Name controltype Status     M     A      t 
P.Value    B
7828     41  15      4  793067       false   cDNA  1.87  8.24  13.23 
0.0341 4.80
2919     16   1      7 1228244       false   cDNA -1.89  9.80 -12.42 
0.0341 4.45
5178     27  20      2  443884      ignore ignore  1.76 11.55  11.77 
0.0341 4.15
2035     11  13      3 1265839       false   cDNA -2.52  8.32 -10.92 
0.0413 3.73
8538     45   8      2  335555       false   cDNA  1.45 10.24  10.10 
0.0440 3.27
10978    57  22      2  463982       false   cDNA  1.45 13.32   9.78 
0.0440 3.08
834       5   7      2  335736       false   cDNA  1.46 12.89   9.53 
0.0440 2.93
6258     33  11      2  334906       false   cDNA -1.34 10.56  -9.45 
0.0440 2.87
11112    58  14      8  314112       false   cDNA  1.33 11.48   9.24 
0.0440 2.74
6651     35  12      3 1264958       false   cDNA -1.99  8.27  -9.22 
0.0440 2.73
490       3  12      2  334575       false   cDNA -1.33 10.15  -9.22 
0.0440 2.73
567       3  21      7  480745      ignore ignore -1.48 11.24  -9.07 
0.0446 2.63
9662     51   2      6 1111090       false   cDNA  1.31  6.09   8.77 
0.0508 2.43
6394     34   4      2 1197400       false   cDNA -1.28  8.58  -8.66 
0.0509 2.35
2407     13   9      7 1197119       false   cDNA -1.36 10.43  -8.33 
0.0553 2.12
9303     49   7      7 1196439      ignore ignore -1.25 10.91  -8.25 
0.0553 2.06
8365     44  10      5  440614       false   cDNA  1.34  7.89   8.23 
0.0553 2.05
3547     19   8      3 1382084       false   cDNA  1.18  8.25   8.21 
0.0553 2.03
1929     10  24      1  790765       false   cDNA -1.26  7.36  -7.98 
0.0581 1.85
9803     51  20      3 1096050       false   cDNA  1.25 10.02   7.90 
0.0581 1.80

#############################################################################
## OS LAB: Two pairs of dye-swap experiments conducted
#############################################################################
TargetsGenePix <- readTargets("OStargets.txt")

>TargetsGenePix

                     SlideNumber               FileName        Cy3        Cy5
OS WT rep1 Sep2005       2630L OS WT rep1 Sep2005.gpr WT control      WT UV
OS WT rep2 Sep2005      2630OL OS WT rep2 Sep2005.gpr      WT UV WT control
OS KO rep1 Sep2005      2631OL OS KO rep1 Sep2005.gpr      KO UV KO control
OS KO rep2 Sep2005       2631L OS KO rep2 Sep2005.gpr KO control      KO UV

snip...

design <- c(1,-1,1,-1)
corfit <- duplicateCorrelation(MAgpr, design, ndups=1, block=c(1,1,2,2))
## > corfit$consensus.correlation
## [1] -0.2315571
fit <- lmFit(MAgpr, design, block=c(1,1,2,2), correlation=corfit$consensus)
fit <- eBayes(fit)
top200 <- topTable(fit,n=200,adjust="fdr")

       Block Row Column    Name controltype Status      M    A     t 
P.Value     B
895       5  14      7 1023591       false   cDNA  1.378 5.45  4.67 
1 -3.67
10580    55  20      4  750226       false   cDNA  1.091 6.03  4.49 
1 -3.69
7293     38  20      5  944409       false   cDNA  1.039 6.39  4.44 
1 -3.70
10117    53  10      5  336470       false   cDNA -1.046 8.07 -4.02 
1 -3.77
3790     20  14      6  894195       false   cDNA -0.786 7.14 -3.90 
1 -3.79
10077    53   5      5  718360       false   cDNA  2.410 5.63  7.22 
1 -3.79
6469     34  13      5  573770       false   cDNA  0.982 6.86  3.74 
1 -3.81
7476     39  19      4  765454       false   cDNA -1.191 6.15 -3.69 
1 -3.82
1981     11   6      5  719193       false   cDNA -0.850 8.22 -3.69 
1 -3.82
6796     36   6      4  905129       false   cDNA -0.748 6.25 -3.63 
1 -3.84
7015     37   9      7 1197111       false   cDNA  0.748 7.90  3.61 
1 -3.84
6361     33  24      1  538420       false   cDNA  1.122 6.14  3.55 
1 -3.85
252       2   7      4  948928       false   cDNA -0.759 7.71 -3.54 
1 -3.85
9467     50   3      3 1449999       false   cDNA  1.321 6.08  5.54 
1 -3.85
2053     11  15      5  622182       false   cDNA  1.414 6.22  5.16 
1 -3.88
10450    55   4      2  634988       false   cDNA  0.815 5.97  3.41 
1 -3.88
940       5  20      4  762123       false   cDNA -0.699 6.28 -3.40 
1 -3.88
9575     50  16      7 1020833       false   cDNA  0.752 7.69  3.39 
1 -3.88
4335     23  10      7 1149905       false   cDNA  1.215 6.47  4.98 
1 -3.89
3292     17  24      4  777258       false   cDNA  0.770 6.25  3.36 
1 -3.89



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