AARDVARK

AARDVARK identifies reversion mutations in DNA sequence data that restore tumor DNA repair and can confer resistance to FDA-approved therapies targeting DNA-repair–deficient tumors.

Key Features:

• Automation: Automated identification of reversion mutations from tumor DNA sequence data.
• Implementation: Implemented as an R package compatible with R version 3.5 or higher.
• Mutation classification: Distinguishes benign polymorphisms from clinically relevant mutations that impact DNA repair pathways.
• Large-scale analysis: Processes large patient-derived tumor sequencing datasets.
• Statistical models: Employs robust statistical models to minimize false positives and false negatives in mutation identification.

Scientific Applications:

• Understanding Mechanisms of Resistance: Pinpoints specific reversion mutations that restore DNA repair and underlie resistance to targeted therapies.
• Personalized Medicine: Identifies patients with reversion mutations who may require alternative therapeutic approaches.
• Drug Development: Provides mutation-level data to inform development of next-generation drugs designed to overcome resistance mechanisms.

Methodology:

AARDVARK scans DNA sequence data with computational algorithms to detect patterns indicative of reversion mutations, systematically analyzes genetic variations to distinguish benign polymorphisms from clinically relevant mutations affecting DNA repair pathways, processes large datasets, and applies robust statistical models to identify reversion mutations while minimizing false positives and negatives.