a LinTIMaT reconstructs a cell lineage tree by integrating CRISPR-Cas9 mutations and transcriptomic data. In Step 1, LinTIMaT infers top scoring lineage trees built on barcodes using only mutation likelihood. In Step 2, for all cells carrying the same barcode, LinTIMaT reconstructs a cellular subtree based on expression likelihood. In Step 3, cellular subtrees are attached to barcode lineages to obtain cell lineage trees and the tree with the best combined likelihood is selected. Finally, LinTIMaT uses a hill-climbing search for refining the cell lineage tree by optimizing the combined likelihood (Step 4). b To reconstruct a species-invariant lineage, LinTIMaT first identifies cell clusters that are preserved in all individual lineages and then performs an iterative search that attempts to minimize the distance between individual lineage trees and the invariant tree topology. As part of the iterative process, LinTIMaT matches preserved clusters in one individual tree to preserved clusters in other individual tree(s) such that leaves in the resulting invariant tree contain cells from all individual studies. See Methods for complete details.