How can I call somatic CNV in tumor samples with no reference (control) samples?

Question

[Pin.Bioinf]

Hello, I know there are many questions about this but none of them have a solution that is valid. I have searched everywhere and did not find a tool to call CNVs (somatic) with tumor only samples. Please help!

[reza]

do you searched about Control-free?

Answer 1

[Kevin Blighe]

You should possibly change your logic about this: many of the programs can call copy number events in a single sample; however, we are not to immediately know if these are somatic or germline. Without the matched normal sample, you can never have 100% certainty that the events that you see are truly somatic. You could use a pooled reference from other unrelated samples, such as 1000 Genomes data. I am aware that Broad Institute also maintains a dataset of CNV (copy number variants) in 'healthy' samples. In fact, here is the Broad's list of healthy CNV: ftp://ftp.broadinstitute.org/pub/GISTIC2.0/hg19_support/

ID  Chromosome  Start   End Flankingstart   Flankingend
CNV.1   1   61735   3214732 61735   3218329
CNV.2   1   3318977 3326796 3318714 3326803
CNV.3   1   3785461 3792719 3781042 3792801
CNV.4   1   4291287 4302161 4286684 4308903
CNV.5   1   4422005 4424098 4421072 4424145
CNV.6   1   4737693 4746636 4737605 4746774
CNV.7   1   4756432 4759428 4754057 4760040
CNV.8   1   4794114 4799166 4793580 4799200
CNV.9   1   4889825 4896261 4889604 4897567
CNV.10  1   5035188 5038051 5031869 5039093
CNV.11  1   5112057 5174017 5102144 5179806
CNV.12  1   5352492 5403585 5347439 5408889
CNV.13  1   5826898 5830967 5820669 5831118
CNV.14  1   5898729 5902850 5898323 5903958
CNV.15  1   6018391 6056168 6014563 6056729
CNV.16  1   6434139 6445278 6433129 6449638
CNV.17  1   6771569 6773752 6771523 6773839

I utilise that data in Part B, here: C: How to extract the list of genes from TCGA CNV data

----------------------------------------------------------

When calling CNAs in tumour samples, you need to be aware of various things:

• normal cell contamination
• ploidy of the tumour
• allele-specific CNA (e.g., one allele may actually be deleted but the other amplified multiple times)

It really helps to have the matched reference for accurately calling somatic CNAs.

Take a look at ABSOLUTE, ASCAT, and FREEC.

Kevin

[jared.andrews07]

To add to Kevin's answer, I've also found the Database of Genomic Variants to have excellent sets of common germline CNVs that can help you filter out many of them. His other points still hold true - having a matched reference is best.