Extended Data Fig. 3: Mass spectrometry analysis of neuronal cultures of C57BL/6J, Ddhd2^−/− and Ddhd2^−/− treated with fatty acyl-CoA supplements.

Global proteomic shifts and rescue effects in Ddhd2^−/− neurons revealed by PCA, hierarchical clustering, and GO enrichment. a, Principal component analysis (PCA) of batch-corrected protein abundance data from C57BL/6J, Ddhd2^−/−, and Ddhd2^−/− neurons treated with either S-CoA or M:P:S-CoA. Each point represents an individual sample, with the outer square indicating replicate identity and inner fill denoting treatment group. PC1 and PC2 account for the greatest variance in the dataset and show clear separation by condition. b, Hierarchical clustering based on Euclidean distance and complete linkage, using normalized and batch-corrected protein abundance data. Samples cluster by experimental group, with M:P:S-CoA-treated Ddhd2^−/− neurons displaying the closest proximity to wild-type samples. c, Gene Ontology (GO) enrichment analysis (cellular component category) of significantly up- or down-regulated proteins in Ddhd2^−/− ± S-CoA or M:P:S-CoA relative to C57BL/6J. Dot size represents the number of enriched proteins; color scale reflects statistical significance (adjusted p-value); and GeneRatio corresponds to the fraction of significant proteins per GO term. N = 5 biologically independent experiments in each condition.