Fig. 2: Electrophysiological features of neuronal stimulation captured by transcriptome-based activity score.

a Activity score distributions compared between stimulated Patch-seq neurons (gold) and unstimulated SMART-seq neurons (violet). The number of cells in each comparison are given as text annotations for each density plot. b Observed D statistics (red line) and empirical distribution from Kolmogorov–Smirnov tests (two-sided) between activity score distributions of Patch-seq and SMART-seq datasets, using permutations of shuffled expression values (n = 1000 permutations per cell type) from all cells represented in a. Boxplots depict median value, box bounds denote interquartile range (IQR), whiskers denote values within ±1.5 x IQR, and points outside of whisker range denote outliers with values ≥1.5 x IQR. c Associations between electrophysiological (e-phys) features and predicted activity (n = 1277 cells). Heatmap shows feature value columns ordered by the mean bootstrap coefficient, and individual neuron rows ordered by ephys-based lasso model prediction of NEUROeSTIMator output (top). Predicted and observed NEUROeSTIMator output shown to the right. Colors represent z-scaled values, with red colors indicating higher values and blue indicating lower values. The dot plot (bottom) shows a summary of coefficients estimated by fitting lasso-regularized linear models between electrophysiology feature value and NEUROeSTIMator output (n = 10,000 bootstrap permutations per feature). Dots represent the mean coefficient estimate across bootstraps, lines indicate standard error across bootstraps. P-values were estimated by counting the number of bootstrap permutations where the coefficient was zero or the opposite sign of coefficients observed from the lasso model fit to all data. Significant features with standard errors that do not cross zero (p < 0.05, unadjusted) are depicted by green-colored dots (bottom). See source data for full statistics and feature descriptions. d Spike train comparison of two Vip/Ptprt/Pkp2 neurons exhibiting representative electrophysiological features of high (red) and low (blue) NEUROeSTIMator predictions (ramp current injected - top panel, membrane potential - bottom panel). e Patch-seq validation of the positive association between input resistance and NEUROeSTIMator predictions in a novel set of human excitatory neurons (n = 25 cells). Pearson’s correlation test (two-sided) statistics annotated; linear fit (orange line). Source data are provided as a Source Data file.