UK biobank versus Genomics England

Question

[zizigolu]

Hi I need some intuition here and thank you for sharing your ideas

Genomics England WGS vcf files are available in pair per participant so there is one vcf file as germline sample and one vcf file as somatic. I have calculated the percentage of 300 Genomics England colon cancer patients carrying a given mutation in KRAS from these 300 germline vcf files. I was going to extend my project to >8000 colon cancer patients in UK biobank. Am I right that germline vcf files in Genomics England are not like UK biobank DRAGEN WGS vcf files because UK biobank WGS DRAGEN vcf files come from germline calling pipeline while in Genomic England come from somatic mutation calling as Strelka caller does.

Please correct me and thanks once more

Answer 1

[Emily]

Germline samples are aligned using Dragen. You can find full details of the pipeline in the GEL cancer genome analysis documentation.

[zizigolu]

Thanks my confusion is if the results from Genomics England germline VCF files (in screenshot) comparable to UKB-RAP WGS DRAGEN VCF files (which likely Germline pipeline has been used to call the variants) ??

I have used these vcf file from Genomics England

[Emily]

I just deleted your image because it contained GEL participant platekeys which is not allowed to be shared. If you have access to the data that means you have completed IG training and you should know this. Please re-read the information on data security.

Please read the documentation I sent you for details on the GEL pipelines, and compare them to any details you have on UKBB.

[zizigolu]

Thanks a million and apologies for unintentional screen sharing

[zizigolu]

Good morning Emily

Please look at page 4 of this GEL documentation

Cancer Analysis Technical Information Document

Which says small variants has been called by Strelka. Having two GEL documentations now, seems to be confusing

[Emily]

Page 18 of that doc:

5 Germline findings

Detection of germline small variants is being performed with the DRAGEN small variant caller v3.2.22. The DRAGEN software incorporates inferred sex into variant calling such that the overall ploidy of the X chromosome is considered (with possible values of 1 or 2 copies), and haploid calls are produced where appropriate. Annotation of detected small variants is performed with Cellbase (v4.7.1 for analysis prior to May 26th 2021, v4.9.5 from May 26th to July 28th 2021 and v4.9.6 from July 28th 2021) with the ENSEMBL (version 90/GRCh38) and ClinVar (June 19 release for analysis prior to May 26th 2021 and January 2021 release after May 26th 2021) databases. Annotation of germline copy number and structural variants is currently not performed.