Fig. 4: Transcriptomic changes in human microglia treated with Lecanemab.
a, Volcano plots showing a gene expression comparison between Lecanemab-treated and IgG1-treated human microglia (n = 6 mice per condition). The number of significant genes per condition is reported in brackets. Padj threshold < 0.05 (two-sided Wilcoxon rank-sum test, P values adjusted with Bonferroni correction based on the total number of genes in the dataset, NS). b, UMAP plot visualizing 22,420 (10,850 IgG1, 11,570 Lecanemab) human microglial cells after the removal of macrophages. Cells are colored according to clusters identified. The assignment of different clusters to distinct cell types or states is based on the previous experimental data from our laboratory14. c, OR and 95% CI for the differential abundance of cell states between Lecanemab-treated (n = 6 mice) and IgG1-treated group (n = 6 mice) using MASC analysis. Points indicate the estimated OR, with horizontal lines representing the 95% CI. Two-sided tests were performed, and exact P values are shown. No significant changes in the proportion of cell states are detected between IgG1 and Lecanemab-treated microglia. d, NES of significantly enriched (Padj < 0.05) WGCNA modules between IgG1 and Lecanemab-treated cells, as identified by GSEA with Padj values indicated. Two-sided P values were adjusted using the BH correction (**Padj < 0.01, ***Padj < 0.001). e, Functional annotations based on GO pathway analyses (MF and BP) using an overrepresentation analysis (one-sided hypergeometric test). Enrichment for a given ontology is shown by q score, with thresholds indicated by red line (q < 0.1) and black line (q < 0.05). The top ten hub genes are shown based on the module eigengene-based connectivity (kME). P values were adjusted using the BH correction. OR, odds ratio; CI, confidence interval; MF, molecular function; BP, biological process; MASC, mixed-effects modeling association of single cells.
