What is the meaning of copy_ratio in reviewed result of ABSOLUTE

Question

[Shixiang]

I downloaded ABSOLUTE example data from http://software.broadinstitute.org/cancer/software/genepattern/modules/docs/ABSOLUTE/2. When I checked the input segment file and result data, I find very confusing column marked as "copy_ratio".

> segtab2 = readr::read_tsv("~/Downloads/ABSOLUTE exampledata/1131213/solid_tumor.segtab.txt")
> head(segtab2)
# A tibble: 6 x 16
  sample Chromosome Start.bp End.bp n_probes length seg_sigma       W copy_ratio modal_cn expected_cn subclonal
  <chr>       <int>    <int>  <int>    <int>  <int>     <dbl>   <dbl>      <dbl>    <int>       <dbl>     <int>
1 solid…          1  3218610 1.44e7     5840 1.12e7   0.00164 0.00394      0.456        2       2.08          0
2 solid…          1 14450545 1.45e7        2 2.46e3   0.0884  0            0.131        0       0.583         0
3 solid…          1 14455748 3.17e7     9063 1.72e7   0.00131 0.00604      0.462        2       2.11          0
4 solid…          1 31682380 3.17e7       40 5.37e4   0.0198  0.00002      0.340        1       1.48          0
5 solid…          1 31740706 3.18e7        4 9.93e3   0.0625  0            0.568        3       2.69          0
6 solid…          1 31751191 3.18e7       35 7.87e4   0.0211  0.00003      0.692        3       3.52          0
# ... with 4 more variables: cancer_cell_frac <dbl>, ccf_ci95_low <dbl>, ccf_ci95_high <dbl>, hz <int>
> segfile = readr::read_tsv("~/Downloads/ABSOLUTE exampledata/SNP6_solid_tumor.seg.txt")
> head(segfile)
# A tibble: 6 x 6
  Sample                       Chromosome    Start      End Num_Probes Segment_Mean
  <chr>                             <int>    <int>    <int>      <int>        <dbl>
1 TCGA-DK-A1A6-01A-11D-A13V-01          1  3218610 14449771       5840       -0.133
2 TCGA-DK-A1A6-01A-11D-A13V-01          1 14450545 14453003          2       -1.94 
3 TCGA-DK-A1A6-01A-11D-A13V-01          1 14455748 31677633       9063       -0.114
4 TCGA-DK-A1A6-01A-11D-A13V-01          1 31682380 31736123         40       -0.558
5 TCGA-DK-A1A6-01A-11D-A13V-01          1 31740706 31750640          4        0.184
6 TCGA-DK-A1A6-01A-11D-A13V-01          1 31751191 31829873         35        0.468
> head(segtab2$copy_ratio)
[1] 0.45600 0.13051 0.46211 0.33972 0.56813 0.69164

As I know, to get copy ratio, we calculate 2^Segment_Mean, which for Segment_Mean -0.133 should be 0.9119964, but ABSOLUTE all computed as 0.5 * 2 ^ Segment_Mean.

How should I understand this?

Thanks, Shixiang

Answer 1

[Shixiang]

I captured function MakeSegObj calculate copy number as 2 ^ Segment_Mean but not 2 * 2^ Segment_Mean. I think this code is not right because the former means copy number ratio. The real problem is that at the end, ABSOLUTE calculate copy_ratio as copy_number / 2, which generated results I show above.

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