Issue with Somatic Insertion Genotyping in Case-Control Mode

[MuratcanMentes]

Hello,

First, I want to express my gratitude for developing xTEA.

I am encountering an issue while using xTEA’s case-control mode to identify somatic transposon (specifically Alu) insertions. Based on my understanding from other issues, the genotype should indicate somatic insertion if it is 1/1 or 0/1 in the tumor and 0/0 in the matched control. However, in my case-control analysis, the resulting VCF file has all genotypes labeled as “./.”.

Could you help me understand why this might be happening? Additionally, are there alternative methods to determine somatic insertions in the resulting VCF file?

Many thanks for considering my request.

[simoncchu]

Hi, case-ctrl mode is used to identify somatic TE insertions. We don't expect a genotype information for somatic insertions. We classify germline ones to heterozygous or homozygous to indicate they are inherited from one or both of the parents. But somatic insertions formed post-zygotic, thus should be absent from both parents.

[MuratcanMentes]

Thank you for your quick response and clarification.

The IGV screenshots of some regions have caused some confusion. Despite xTEA predicting these regions as somatic insertions, I observed clipped reads and discordant reads in the matched control. Could you help me understand the reason for this discrepancy? Did I misunderstand xTEA's results? Does xTEA identify the regions with confirmed insertions or potential somatic insertions?

Thank you for your time and assistance.

[simoncchu]

If this is the case, then it's a false positive. Just not sure why this is reported, since the signal in control is strong.