Katdetectr: An R/Bioconductor package utilizing unsupervised changepoint analysis for robust kataegis detection

Abstract

Motivation: Kataegis refers to the occurrence of regional hypermutation in cancer genomes and is a phenomenon that has been observed in a wide range of malignancies. Robust detection of kataegis is necessary to advance research regarding the origins and clinical impact of kataegis. Multiple kataegis detection packages are publicly available; however, the performance of their respective approaches have not been evaluated extensively. Here, we introduce katdetectr, an R-based, open-source, computationally fast, and robust package for the detection, characterisation and visualisation of kataegis. Results: The performance of katdetectr and five publicly available packages for kataegis detection were evaluated using an in-house generated synthetic dataset and an a priori labelled pan-cancer dataset of whole genome sequenced malignancies. The performance evaluation revealed that katdetectr has the highest accuracy and normalized Matthews Correlation Coefficient for kataegis classification on both the synthetic and the a priori labelled dataset. Katdetectr is in particularly more robust for kataegis detection within samples with a high tumour mutational burden. Availability and Implementation: Katdetectr imports standardised variant calling formats (MAF and VCF) as well as standard Bioconductor classes (GRanges and VRanges). Katdetectr segments genomic variants utilising unsupervised changepoint detection and the Pruned Exact Linear Time search algorithm. Kataegis foci are flagged based on the historical definition, namely that a kataegis foci is a continuous segment harbouring ≥6 variants and has a mean intermutation distance ≤1000 bp. Additionally, the implementation of changepoint detection utilised by katdetectr results in fast computation. Furthermore, katdetectr is available on Bioconductor which ensures reliability, and operability on common operating systems (Windows, macOS and Linux). Katdetectr is available on Bioconductor at https://www.bioconductor.org/packages/devel/bioc/html/katdetectr.html and on GitHub at https://github.com/ErasmusMC-CCBC/katdetectr. All code used for the performance evaluation is available on GitHub at: https://github.com/ErasmusMC-CCBC/evaluation_katdetectr

Katdetectr: an R/bioconductor package utilizing unsupervised changepoint analysis for robust kataegis detection

“…Additionally, Katdetectr has been implemented in a flexible manner, which allows Katdetectr to expand in the field of kataegis. Katdetectr is available on Bioconductor [ 21 ] and on GitHub [ 22 ].…”

“…For additional examples and more hands-on technical instructions, we refer to the accompanying vignette ( Supplemental Vignette ) or the online Bioconductor repository [ 21 ].…”

Whole-genome mapping of APOBEC mutagenesis in metastatic urothelial carcinoma identifies driver hotspot mutations and a novel mutational signature

“…Alignment and pre-processing of WGS data, detection of genomic subtypes, HR deficiency, MSI, structural variants, chromothripsis events, APOBEC mutagenesis, and pathway activity have been previously described 4,10,49,50 . Mutational signatures and kataegis were detected with MutationalPatterns v3.10.0 51 and Katdetectr v1.2.0 52 . APOBEC enriched tumors (adj.…”