The LMA workflow consists of the following steps. First, all possible cell fate patterns are enumerated. Second, the occurrence of each pattern within the observed lineage trees is counted (triplet pattern E is shown here as an example). Third, the cell fate labels at the leaves of the trees are randomly shuffled to obtain a resampled set of trees with no fate correlations. This process is then repeated across many resamples. To identify the higher-order motifs that span multiple cell divisions, the shuffling process is done in a manner that preserves sub-pattern frequency (STAR Methods). The occurrence of each cell fate pattern is then counted for each resample. Fourth, the count in the observed lineage trees is compared with the distribution of counts across resamples, whose average is approximately equal to the expected count if there were no fate correlations. Finally, overrepresented patterns are classified as lineage motifs, which represent possible committed progenitors or extrinsic interactions.
