Metabolomics with GO and GO-CAM

Bridging metabolite lists to GO functions and processes through ChEBI and Rhea

AI Gene Review · projects/METABOLOMICS · 2026

Bottom line

  • A working bridge: metabolite → Rhea → GO MF → human enzymes → GO BP, with closure-aware enrichment.
  • The obstacle is identifiers: exact ChEBI matching connects 8/64 MTBLS1 metabolites; protonation + structure normalization reaches 58/64.
  • Four MetaboLights studies: 53–91% coverage, study-specific GO processes. Gaps: complex lipids, GO-CAM causal tracing, Reactome cross-check.

Why GO is absent from metabolomics

  • Standard interpretation: KEGG / SMPDB pathway ORA, MSEA, mummichog for untargeted MS (packaged in MetaboAnalyst).
  • GO annotates gene products, so it says nothing about a list of ChEBI ids out of the box.
  • But GO MF terms are enzyme activities, and Rhea reactions are written in ChEBI. ChEBI is the bridge.

The bridge and where it breaks

Normalization is decisive in every study

What GO adds over KEGG (MTBLS1, same test)

KEGG pathway GO molecular function GO biological process
Ala, Asp & Glu metabolism amino-acid transaminase amino acid metabolic process (4.3×, FDR 9e-44)
Citrate cycle (TCA) L-/D-amino-acid oxidase dicarboxylic acid metabolic process (6.0×)
Pyruvate metabolism amino-acid racemase amino acid transport (5–7×)
Nicotinate & nicotinamide primary methylamine oxidase proteinogenic amino acid metabolism (4.2×)

Serum LC-MS study MTBLS90 instead returns lipid metabolic process (2.9×, FDR 3e-89). GO resolves specific activities and processes, not only pathway buckets.

Status and next steps

  • Done: probe pipeline (projects/METABOLOMICS/probe/), two-tier normalization, KEGG / GO-MF / GO-BP enrichment, 4 studies.
  • Next: complex lipids (LIPID MAPS / SwissLipids); Reactome as a curated BP cross-check; GO-CAM causal trace (Approach B); feed implicated reactions to Reactome black-box gap filling.
  • Planned: interactive demo (static showcase + FastAPI app), see DEMO-PLAN.md.

Read more: projects/METABOLOMICS.md · projects/METABOLOMICS/CROSS-STUDY.md