Section 9 Reproducible pathway and enrichment analyses

Pathway and enrichment analyses of the milk effects in Sections 4 and 5, run offline for each trial, visit, contrast, and direction of effect, with the features at P < 0.05 as input. Negative enrichment ratios mark down-regulated pathways.

9.1 Interactive pathway explorer

Every enrichment table in the supplementary materials (Tables S2–S7), including the arm-stratified runs, as a dot plot and table, filtered by analysis, trial, and visit. The app runs R in the browser, so the first load takes a moment. Open it in a new tab.

9.2 Targeted-metabolome enrichment (Table S3)

Table S3 in full: over-representation of the SMPDB small-molecule and lipid metabolite sets among the targeted metabolites, computed in MetaboAnalystR against the whole measured human metabolome as background (table_s3_tertiary_msea_full.csv). fdr_native is the Benjamini–Hochberg FDR that MetaboAnalystR reports for each run.

9.3 Pathways enriched on both metabolomics platforms

Pathways with Q < 0.05 in the targeted (Table S3) or untargeted (Table S5) enrichment and P < 0.05 in the other, listing every trial, visit, contrast, and direction with P < 0.05 on either platform.

9.4 Untargeted-metabolome Mummichog enrichment (Table S6)

Table S6 in full: Mummichog pathway enrichment of the untargeted milk features, matched to the human_mfn network at 10 ppm, by trial, visit, contrast, direction, and ionization mode, for the pathways with P < 0.05 (table_s6_mummichog_full.csv). FDR is Benjamini–Hochberg-adjusted within each run.

9.4.1 Putative feature annotations

Mass-based putative names (MSI level 3) of the FDR-significant untargeted milk features.

9.5 Proteome Gene Ontology enrichment (Table S7)

Table S7 in full: over-representation of Gene Ontology Biological Process terms among the proteins with P < 0.05, using clusterProfiler::enricher with each measured UniProt protein counted once and all proteins measured in the trial and contrast as background, for the terms with P < 0.05 and Storey q < 0.20 (table_s7_proteomics_go_full.csv). fdr is Benjamini–Hochberg-adjusted. The second table repeats the terms with Q < 0.05 with the contributing UniProt accessions.