CNV analysis from vcf file

Question

[javiergonzalo.ocejo]

Dear colleagues,

I'm a rookie in NGS analysis. I have several patients who have been studied in other centers: targeted panels, clinical exome or WES. The problem is that in some cases, the analysis of these studies did not include CNVs. Is it posible from the generated files (vcf, fastq) analyze if there is any CNV in those samples?. Thank you very much for your help. Kind regards, Javier

[Ram]

Have you tried searching the site/search online in general?

[Garan]

Align the fastq files against the reference genome - BWA or similar against GRCh.v.38 (or 37) - you might want to run the full GATK best practices pipeline. If the sequencing was all done as part of a batch (same flowcells, same library prep) you can run something like ExomeDepth or XHMM (read depth based callers) / Breakdancer (read-pair) / GATK 4 GermlineCNVCaller. Adjust for false positives either by checking against known sample CNVs (for example GIAB CNV calls on NA12878 or Ashkenazim Trio) and/or common batch specific CNVs.

Answer 1

[gab]

To get data about CNVs you need usually .bam files which are essentially alligned FASTA foramet reads. So if you only have FASTQs you'll have to allign them. I used cnvkit to get the results, it has a very good user manual and it is still mantained. However to complete the analysis properly you'll need both case and normal samples, else you'll have to infer CNVs aginst a reference genome, loosing statistical power and correction based on the patient's characteristics.