EvAM-Tools

EvAM-Tools models cancer progression and evolutionary event accumulation using directed acyclic graphs, matrices of mutual hazards, and genotype composition specifications to simulate and analyze genotype evolution.

Key Features:

• Model fitting and outputs: Provides fitted models, transition matrices between genotypes, and probabilities of evolutionary paths.
• Random model generation: Generates random cancer progression models for exploration of hypothetical evolutionary trajectories.
• Customizable models: Allows construction and modification of directed acyclic graphs of restrictions, matrices of mutual hazards, and genotype compositions.
• Data generation with error simulation: Produces synthetic data from models incorporating user-specified observational and genotyping errors.
• Implementation: Implemented in R and C.

Scientific Applications:

• Oncology research: Models mechanisms of cancer progression and genotype evolution to inform studies of tumor development.
• Evolutionary biology: Analyzes the accumulation of genetic events over time in evolving populations.
• Hypothesis generation and testing: Facilitates hypothesis generation and testing via simulation and fitted-model analyses.
• Therapeutic development: Supports preclinical investigations relevant to targeted therapy development by characterizing evolutionary trajectories.

Methodology:

Constructs directed acyclic graphs representing restrictions on evolutionary paths, defines matrices of mutual hazards to capture genotype interactions, specifies genotype compositions, fits models to produce fitted models, transition matrices and path probabilities, and generates synthetic data with observational and genotyping errors.