Cassiopeia

Cassiopeia reconstructs phylogenetic trees from single-cell lineage tracing data produced by CRISPR/Cas9-based editing to infer cellular lineage relationships.

Key Features:

• Phylogeny Reconstruction: Implements multiple algorithms for tree construction, including a greedy algorithm based on multi-state compatibility, an exact Steiner-Tree solver, a combined greedy/Steiner approach (Cassiopeia), Neighbor-Joining, and Camin-Sokal Maximum Parsimony.
• Scalable Maximum Parsimony Approaches: Provides scalable maximum parsimony methods optimized for large single-cell lineage datasets.
• Simulation Framework: Includes a simulation framework to evaluate algorithm performance and to explore lineage tracer design parameters.
• Benchmarking with Complex Datasets: Has been benchmarked on an experimental dataset of 34,557 human cells traced over 15 generations.

Scientific Applications:

• Large-scale mammalian lineage tracing: Enables inference of cellular lineage relationships in large single-cell CRISPR/Cas9 lineage tracing experiments.
• Cellular evolution and development studies: Supports analysis of lineage relationships to investigate cellular evolution and developmental trajectories.

Methodology:

Uses greedy multi-state compatibility, an exact Steiner-Tree solver, a combined greedy/Steiner approach (Cassiopeia), Neighbor-Joining, Camin-Sokal maximum parsimony, scalable maximum parsimony implementations, and a simulation framework for evaluation.