Fig. 2: MorphDiff predicts changes in cell morphology with genetic perturbations. | Nature Communications

Fig. 2: MorphDiff predicts changes in cell morphology with genetic perturbations.

From: Prediction of cellular morphology changes under perturbations with a transcriptome-guided diffusion model

Fig. 2

a Visualization of the generated outputs from MorphDiff and baseline methods for the SREBF1. The corresponding information for the original channels and fluorophores can be found in Supplementary Table 1, and the weights of composition are detailed in the Evaluation Setup part of the Methods section. The scale bar is 20 μm. b Performance benchmarking on the JUMP OOD set. Each method was evaluated 10 times for robust assessment. Methods requiring reference control DMSO morphology as input used 10 distinct control image groups from independent plates (n = 10 biological replicates), while methods without this requirement used 10 sampling iterations with different random seeds. Linear normalization was conducted on the reciprocals of FID, CMMD, and on the other three metrics separately to convert their values to the range of 0–1. A larger value indicates better performance. One-sided Wilcoxon signed-rank test with Bonferroni correction was conducted between MorphDiff(I2I) and other methods. “*” indicates that MorphDiff(I2I) surpasses the baseline method with a p value <0.05. The “ns” represents the situation of no significant difference. Data are presented as mean values ± SD. c UMAP visualization of CellProfiler features for IMPA and MorphDiff(G2I) under two genetic perturbations. DMSO (Dimethyl sulfoxide) serves as the untreated control. d CellProfiler feature distributions comparing ground truth with IMPA, MorphDiff(G2I), and MorphDiff(I2I) outputs for RAC1 perturbation. Abbreviations: E ERSyto, EB ERSytoBleed, H Hoechst, Pg Ph_golgi, LQ lower quartile, Var variance, Tex texture, Corr correlation, Int intensity. e The two-sided Wilcoxon signed-rank test results to test the difference between the generated and ground-truth CellProfiler features. The y-axis indicates the proportion of generated CellProfiler features not significantly differ from the ground-truth CellProfiler features through a Wilcoxon signed-rank test (p  value >0.05). 232 features are tested in total. f The heatmap of the correlation between the CellProfiler features of the ground-truth morphology, MorphDiff(G2I)-generated morphology, and IMPA-generated morphology with L1000 gene expression. Source data are provided as a Source data file for (b–f).

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