Extended Data Fig. 4: Structure-based velocity estimation.

a, b, For genes that are observed only outside of the steady state, such as genes upregulated late in the chromaffin differentiation (a) or downregulated early in the Schwann cell precursors (b), gene-relative γ fit is likely to deviate from its steady-state value. c, d, To correct for such effects, a structure-based γ fit will first predict γ for every gene based on its structural parameters, and then use the k most correlated genes in the dataset to adjust M value (\(M={\mathrm{log}}_{2}({u}_{{\rm{o}}}/{u}_{{\rm{s}}{\rm{s}}})\), where uss is the unspliced counts predicted from spliced counts under steady-state, and uo is the observed unspliced count) using robust mean, and re-estimate γ. e, Scatter plot comparing gene-relative and structure-based γ estimates, with coloured circles highlighting γ adjustments for genes downregulated early in SCPs (blue) and upregulated late in chromaffin cells (green). The values are shown on a natural log scale. f–i, Cell expression velocity in the chromaffin E12.5 dataset, based on the structure-based γ estimates, shown on the first five PCs.