Tumor-Only Analysis with MesKit

[sarah-grn]

Hi,

I am interested in using MesKit to analyze the intra-tumor heterogeneity of my multi-region tumor WES samples. However, I do not have matched normal samples.

I know that matched normal samples are usually used to distinguish somatic mutations from germline variants, but I was wondering:

• Can MesKit be used with tumor-only samples?
  -If so, what is the recommended approach to filter germline variants?
  -Are there any specific preprocessing steps or parameters recommended for tumor-only analysis?

Thank you for your help!

[Niinleslie]

@sarah-grn Hello and thanks for your interest. To address your queries:

1. Can MesKit be used with tumor-only samples?
   Yes. However, please note that MesKit focuses on downstream analysis, we recommend ensuring that your input data is thoroughly preprocessed to minimize false positives.

2. Filtering germline variants without matched normal samples:
   While public databases like gnomAD and ExAC can be helpful references for filtering germline variants, they may not be sufficient on their own when matched normal samples are unavailable.

1. You may leverage tumor-specific variant callers designed for tumor-only analysis (e.g., Mutect2's tumor-only mode).
2. Filtering out common germline variants using public databases (e.g., gnomAD, ExAC) and other resources.
3. Applying quality control metrics (e.g., depth, allele frequency) to further refine your variant list.