ABOUT affymetrix genotyping console (GTC) software and TCGA CNV workflow

Question

[xingyu]

The TCGA CNV workflow uses Birdsuite to estimate raw copy number (CN). The affymetrix genotyping console (GTC) use similar algorithm developed by broad. Is GTC used to estimate raw CN, too? Otherwise, could GTC output files that could be input files for DNAcopy package used by TCGA in the copy number segement stage.

[Kevin Blighe]

Yes, GTC calculates raw CN. For DNAcopy, why not take a look at the desired input?

library(DNAcopy)
data(coriell)
head(coriell)

        Clone Chromosome Position Coriell.05296 Coriell.13330
1  GS1-232B23          1        0            NA      0.207470
2  RP11-82d16          1      468      0.008824      0.063076
3  RP11-62m23          1     2241     -0.000890      0.123881
4  RP11-60j11          1     4504      0.075875      0.154343
5 RP11-111O05          1     5440      0.017303     -0.043890
6  RP11-51b04          1     7000     -0.006770      0.094144

So, CN here is represented as log ratios.

[xingyu]

Thank you for your reply. I have been reviewed DNAcopy package and the instruction of it. I noticed that the CN value is log2 ratio in the coriell data. I used GTC and outputed integer CN value as the following. DO I miss something ?

[Kevin Blighe]

HI, if the copy number from GTC is 1, this equates to a log2 ratio of -1. Please see:

log2(1 / 2)
[1] -1

Why we use 2? - 2 is the normal copy number value, relating to the maternal and paternal allele.

If, instead, you have a disease sample, then you can define the ratio as:

log2(disease CN / healthy CN)

[xingyu]

I still have questions of the log2 ratio value of GTC and DNAcopy. It's noticeable that DNAcopy's log2 ratio value is continuous, but GTC's log2 ratio value is integer. GTC may do something (eg. HMM) to estiamte integer CN state to replace the continuous log2 ratio value. Otherwise, the integer CN state value that I shown may be not as input of DNAcopy.

PS: My purpose is to use the output of GTC to gain raw CN. subsequently, take advantage of DNAcopy and GISTIC to get the gene level of CNV as the following.