BubbleTree

BubbleTree estimates cancer cell purity, tumor ploidy, allele-specific copy number, and clonality from next-generation sequencing (NGS) data to characterize intratumoral heterogeneity and identify subclonal populations.

Key Features:

• Comprehensive clonality characterization: Estimates cancer cell purity, tumor ploidy, allele-specific copy number, and clonality from NGS data.
• BubbleTree graph visualization: Represents results as a BubbleTree graph to visualize intratumoral heterogeneity and subclonal structure.
• Automated interpretation heuristic: Applies a three-step heuristic divide-and-conquer method to automate interpretation of the BubbleTree graph.
• Subclone and polyploidy detection: Demonstrated superior performance over THetA2, ABSOLUTE, AbsCN-seq, and ASCAT for identifying subclonal populations and detecting polyploidy in simulated and patient-derived data.
• Clonality tracking: Tracks changes in clonality between primary and metastatic tumor samples.
• Variant timing: Dates somatic single nucleotide variants (SNVs) and copy number variants along tumor clonal evolution trajectories.

Scientific Applications:

• Intratumoral heterogeneity analysis: Characterizes heterogeneous tumor karyotypes and allele-specific copy number landscapes.
• Clonal evolution studies: Reconstructs clonal trajectories and dates somatic SNVs and copy number events along those trajectories.
• Treatment response assessment: Assesses clonal dynamics to evaluate responses to therapy.
• Metastasis research: Investigates clonality changes and the genetic basis of metastatic progression.

Methodology:

Implemented in R; analyzes NGS data to estimate allele-specific copy number, purity, ploidy, and clonality; uses a three-step heuristic divide-and-conquer procedure for automated interpretation and produces BubbleTree graph visualizations.