MACH2

MACH2 systematically enumerates all plausible migration histories of metastatic cancer cells by exactly solving the Parsimonious Migration History with Tree Refinement (PMH-TR) problem from clone phylogeny and the location of extant clones.

Key Features:

• Exact enumeration: MACH2 exactly solves PMH-TR to enumerate all plausible migration histories rather than returning a single optimal solution or probabilistic approximations.
• Configurable parsimony criteria: MACH2 allows specification of both the order and the set of criteria to include during optimization, including migration count, comigration count, and a novel criterion minimizing clones unobserved in their inferred location of origin.
• Summary graph: MACH2 includes a summary graph to identify high-confidence migrations across the solution space.
• Visualization companion: MACH2-viz provides interactive visualization and exploration of MACH2 solution spaces.

Scientific Applications:

• Metastasis research: MACH2 advances understanding of cancer cell migration history to support metastasis research and therapy development.
• Uncertainty quantification: MACH2 detects extensive uncertainty in migration history inference for non-small cell lung, ovarian, and prostate cancers.
• Validation against orthogonal data: MACH2 infers migration histories consistent with orthogonal experimental data on real tumor datasets.
• Method benchmarking: MACH2 outperforms existing parsimony-based methods on simulated tumors with known ground truth, particularly when prioritizing the unobserved clone criterion.

Methodology:

MACH2 exactly solves the Parsimonious Migration History with Tree Refinement (PMH-TR) problem through systematic enumeration of all plausible migration histories from clone phylogeny and extant clone locations, with configurable optimization criteria including migration minimization, comigration minimization, and minimization of clones unobserved in their inferred location of origin.