Dear all,
Often in cáncer related studies people use cut offs for cnvs (e.g. >=2x fold change for duplications and <=0.5 fold change for deletion). It is clear why it is done for deletions, the variant in tumor suppressor has to be homozygous, but why do they use this threshold for amplifications? Expression changes significantly even with copy number 3 instead of 2...
The main version so far is because of level of noise (CN3 can be less reliably detected than CN4), but when we look at sub-clones, it becomes less obvious. Also, modern tools provide methods for False positives assessment.
So, the question is: why do everybody does hard thresholding for amplifications, is there a hidden biological sense or it is just because bioinformatics methods and data were not reliable back in times?
Example of research that uses only high copy-numbers: https://www.nature.com/articles/nature22071, "Percentage of samples with protein-affecting aberrations in candidate driver genes, grouped by pathway: substitution/indels (blue), structural variants (red), copy number amplification (copy number > 5, yellow), homozygous deletion (green). "
For the reference: expression of cancer driver genes vs copy-number https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428069/bin/41598_2017_219_Fig2_HTML.jpg or https://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-019-0909-5/figures/1
