Extended Data Fig. 6: TOME edges nominated by k-NN versus RNA velocity-based heuristics are largely concordant.

a, Histogram of all potential edge weights calculated by RNA velocity. The y-axis is on a log2 scale. Edges with weights above 0.2 (red line) were retained. b, After calculating the transition probability for individual cells between adjacent time points using scVelo⁹⁷, the same strategy of creating the edges was performed after randomly shuffling the cell-state annotations for cells within each time point, followed by repeating this process 1,000 times, resulting in a null distribution of edge weights. After permutation, less than 1% of potential edges are assigned weights greater than 0.2 (red line). c, Ignoring edges prior to E6.5 as well as between E8.5a and E8.5b (see text), out of 15,261 potential edges, there were 123 edges nominated by the k-NN strategy only (weight > 0.2), and 75 edges nominated by the RNA velocity strategy only (weight > 0.2), and 392 nominated by both strategies. d, Directed acyclic graph showing inferred relationships between cell states across early mouse development. Layout identical to Fig. 2c. Each row corresponds to one of 94 cell-type annotations, columns to developmental stages spanning E3.5 to E13.5, nodes to cell states, and node colors to germ layers. Edges nominated with weights above 0.2 by RNA velocity only are shown in red, by k-NN in blue, and by both strategies in purple. ExE: extraembryonic. PNS: peripheral nervous system. MHB: midbrain–hindbrain boundary. Di: diencephalon.