We are trying to develop a method to call somatic CNV from cfDNA (cancer patient) with control.
However, I can't think of any method that have enough sensitivity to do that. Even we can track the allele frequency in the original library with the barcoding, the AF is pretty low (probably less than 1%). Even the copy number of somatic CNV is high (say 8 copies), the copy number is still diluted to 8% increases (8 * 1%) and highly unlikely to be detected.
Someone suggests that we can target multiple amplicons that are nearby (say EGFR exon1, exon2 and exon3) and use them as sliding windows(fragments). Then calculate their depth on both patient cfDNA and healthy cfDNA and apply t-test.
Still, I don't think this method is valid due to lack of sensitivity (too little tumor DNA fragment in cfDNA).
Am I making sense and is there any other method to do this? Any comments are appreciated.