To explain why we are only seeing such a small coverage increase, we need to turn to our good friend mathematics !
- If a 3 copies state correspond to 60x of coverage.
- we expect 2 copies at 40x
- 1 copy at 20x
- and 0 copy at 0X
But here the cellularity variable is missing. We estimated a cellularity of ~ 50% which mean that half reads observed in tumor come from the normal cells (30x). So if focus only on reads that really come from tumor cells we would expect:
- If a 3 copies state correspond to 30x of coverage (60x - 30x of normal).
- we expect 2 copies at 20x
- 1 copy at 10x
- and 0 copy at 0X
And now if we focus on all the read present in the tumor sample:
- the 3 copies state corresponds to 30x of read from the tumor cells + 30x from normal cells = 60x.
- the 2 copies state corresponds to 20x of read from the tumor cells + 30x from normal cells = 50x.
- the 1 copy state corresponds to 10x of read from the tumor cells + 30x from normal cells = 40x.
Mathematics is the key !