Benchmarking tools for matched germline-tumor variant calling in circulating tumor DNA using semi-synthetic data

Bartelds, Boudewijn (2024) Benchmarking tools for matched germline-tumor variant calling in circulating tumor DNA using semi-synthetic data. Bachelor's Thesis, Biology.

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Abstract

Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) within cell-free DNA (cfDNA) shows promise for cancer detection and characterization. However, ctDNA is only a small portion of cfDNA, thereby needing highly sensitive bioinformatics tools known as variant callers to identify mutations. This study benchmarks six variant callers (VarDict, LoFreq, VarScan2, MuTect2, Strelka2 and Octopus) using semi-synthetic NGS data with known spiked variants to create a germline-tumor matched variant calling pipeline. Variant callers were evaluated for sensitivity and precision when detecting single nucleotide variants (SNVs) and insertions/deletions (indels) at varying allele frequencies (VAFs). Results indicated that VarDict demonstrated the highest overall sensitivity, while LoFreq provided the best balance between sensitivity and precision, as reflected in its highest F1 score of 0.81. VarScan2 also performed well in both metrics. Contrarily, Mutect2, Octopus, and Strelka2 showed lower sensitivity and precision. The study concludes that LoFreq and VarDict are particularly effective for detecting low-frequency variants in cfDNA, highlighting their potential for clinical applications for cancer genomics. These results suggest that a sensitive method for matching germline and tumor variant calling is feasible , which could help improve the current ctDNA-based diagnostics.

Item Type:	Thesis (Bachelor's Thesis)
Supervisor name:	Veltmaat, N.
Degree programme:	Biology
Thesis type:	Bachelor's Thesis
Language:	English
Date Deposited:	04 Jun 2024 07:35
Last Modified:	04 Jun 2024 07:43
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/32512

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