About the case-control analysis in Illumina Short-read WGS Data

[recepyilmaz01]

Hello,
Thanks for developing xTEA.

As a junior researcher aiming to improve my skills in the field of bioinformatics, I have encountered an issue while utilizing xTEA's case-control mode to identify possible somatic transposon insertions. When I checked the resulting regions in IGV, in several regions, I found the control samples exhibit longer and more clipped reads compared to the case samples. What could be the reason for this? As an example, I am dropping screenshots from the IGVs.

Would you kindly help me to find a potential solution to my problem?

Many thanks for considering my request.

[simoncchu]

It looks like there are allele dropouts in the case. See the two heterozygous snps on the right of the screenshot.

[recepyilmaz01]

Thanks for the reply.

Based on our findings, the allele frequency in the tumor (case) and matched normal (control) samples was determined to be 0.545. How should we interpret an allele frequency of 0.545 in the context of potential allele dropout? Specifically, can we conclude that despite possible allele dropout in the tumor sample, there is an insertion in the region? Or should this insertion in the tumor sample only be considered a sequencing artifact?

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tSVLEN	TSD	TSDLEN	SUBTYPE	STRAND	AF	INS_INV	REF_REP

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236	+AAAACCAAGGTCAT	14	two_side_tprt_both	+	0.545454545	Not-5prime-inversion	not_in_Alu_copy

[simoncchu]

It's a germline insertion. That's why you observed it in both the case and control. I mean in the tumor sample, there is an allele dropout, thus the VAF is lower than in the control.