KataegisPortal

KataegisPortal detects and visualizes kataegis events in genomic data using R to identify localized clusters of single nucleotide variants (SNVs) and to study APOBEC-mediated cytosine deamination and mutational processes in cancer whole-genome sequencing (WGS).

Key Features:

• Detection of Localized Hypermutations: Identifies loci with kataegis characterized by clustered SNVs and sequence contexts consistent with APOBEC enzyme activity (cytosine deamination).
• Visualization Capabilities: Provides utilities for visualizing hypermutation clusters to support interpretation of mutational patterns.
• Integration with Whole-Genome and Multiregion Sequencing: Applies to WGS and multiregion WGS datasets to interrogate intratumour heterogeneity and evolutionary trajectories.
• Annotation of Hypermutation Loci: Uses computational algorithms to pinpoint and annotate regions with concentrated mutational activity indicative of kataegis.
• Correlation with Biological Pathways: Enables analyses of associations between hypermutation events and pathways such as MAPK regulation of APOBEC enzymes.

Scientific Applications:

• Ovarian clear cell carcinoma (OCCC) analysis: Applied to multiregion WGS from OCCC patients to delineate spatial and temporal tumour heterogeneity.
• APOBEC-mediated mutagenesis characterization: Detects kataegis events attributed to APOBEC3A and APOBEC3B and supports inference of their timing, including early occurrence in OCCC pathogenesis.
• Tumour evolution studies: Supports investigation of punctuated evolution models and links between kataegis, dynamic mutagenesis, and macroevolutionary events such as aneuploidy acquisition.
• Clinical correlation analyses: Facilitates linking APOBEC expression patterns with prognosis and immune response metrics.

Methodology:

Computational methods explicitly include whole-genome sequencing analysis to capture genetic alterations, computational annotation and pinpointing of regions with concentrated mutational activity indicative of kataegis, and correlation analyses between hypermutation events and biological pathways such as MAPK regulation of APOBEC enzymes.