Estimation of cell lineage trees by maximum-likelihood phylogenetics
Jean Feng, William S. DeWitt III, Aaron McKenna, Noah Simon, Amy D. Willis, Frederick A. Matsen IV
CRISPR technology has enabled cell lineage tracing for complex multicellular organisms through insertion-deletion mutations of synthetic genomic barcodes during organismal development.
This research proposes a statistical framework for the mutation process and develops methodology to estimate tree topology, branch lengths, and mutation parameters using penalized maximum likelihood estimation applied iteratively.
A key advancement involves assuming barcode evolution follows a molecular clock, enabling inference of relative ordering across parallel lineages — a capability exceeding existing techniques that only order nodes within single lineages.
Analysis of transgenic zebrafish data validated the approach, demonstrating consistency across samples while confirming recognized developmental patterns.