C. elegans surveillance immunity

Reviewing GO annotations for 18 genes of a nematode immune system

AI Gene Review · projects/CAEEL_SURVEILLANCE_IMMUNITY · 2025–2026

Bottom line

  • Worms have no NF-kB, inflammasome or adaptive immunity; they detect infection by sensing damage to their own translation, mitochondria and proteasome.
  • We reviewed every GO annotation on 18 genes (p38 MAPK cascade, ZIP-2/CEBP-2, DAF-16, DBL-1, epidermal STA-2/NIPI-3, effectors): 680 GOA rows + 11 NEW.
  • 85% accepted. The errors that remained were mammalian biology transferred to the worm: adaptive immunity, JAK-STAT, TLR, hormone receptor, and catalysis by a pseudokinase.

Why this system

  • Surveillance immunity: the host asks "what is wrong with my cell?" rather than "what is the pathogen?"
  • P. aeruginosa exotoxin A blocks translation → ZIP-2 protein accumulates → ZIP-2 + CEBP-2 induce irg-1.
  • The NSY-1 → SEK-1 → PMK-1 p38 cascade is the central hub; ATF-7 and SKN-1 are its transcriptional outputs.
  • A pathway without pattern recognition is where annotations inherited from mammalian orthologs are most likely to be wrong.

The pathways, and what the review corrected

Scope: three tiers, 18 genes

Tier Genes GOA rows
p38 MAPK core pmk-1, sek-1, nsy-1, tir-1, atf-7, skn-1 303
Surveillance zip-2, cebp-2, irg-1, elt-2, hlh-30, fshr-1 151
Other pathways daf-16, dbl-1, sta-2, nipi-3, lys-7, clec-60 226

Counts are non-NEW rows in genes/worm/<gene>/<gene>-ai-review.yaml. The project page's "549+" predates the final reviews.

Decisions per gene

Bar totals include proposed NEW rows, so they run higher than the non-NEW tier counts on the previous slide (e.g. surveillance tier 158 here vs 151).

A pseudokinase is not a kinase

NIPI-3 review: ATP binding is kept (pseudokinases often retain it); protein kinase activity (GO:0004672, IEA from the InterPro kinase domain) is removed.

Findings

  1. Ortholog transfer: STA-2 JAK-STAT signalling REMOVE (no JAKs in worms); TIR-1 TLR-pathway term REMOVE; FSHR-1 hormone rows REMOVE; DAF-16 adaptive immune response → innate (MODIFY).
  2. Inactive enzymes: NIPI-3 protein kinase activity REMOVE; LYS-7 lysozyme activity over-annotated (no active site).
  3. protein binding: ZIP-2, CEBP-2, DAF-16, SKN-1, TIR-1, STA-2 rows → specific MF (e.g. GO:0046983 dimerization).
  4. Gaps filled: 3 NEW rows on CLEC-60 (1 GOA row), 6 on HLH-30.

The six satellite documents

  • Priority 2 (zip-2 … fshr-1): gene-by-gene review + line-level edit list.
  • Priority 3 (daf-16 … clec-60): detailed analysis, executive findings, checklist.
  • All 18: consolidated recommendations by action.
  • Written 2025-12-29, before the YAML was finalised. Only part was adopted: ELT-2 and HLH-30 generic transcription terms stayed ACCEPT; the pseudoenzyme, JAK-STAT and CLEC-60 calls were adopted.

Status and next steps

  • ✅ 18/18 reviews written and rendered; pathway summary in projects/CAEEL_SURVEILLANCE_IMMUNITY/.
  • ⬜ Reconcile the pathway summary with the reviews (it still calls LYS-7 an active lysozyme and NIPI-3 a Ser/Thr kinase).
  • ⬜ Decide the open satellite calls (ELT-2/HLH-30 generic terms, TIR-1 NADase UNDECIDED).
  • ⬜ Refresh stale counts and UniProt IDs on the project page.

Read more: projects/CAEEL_SURVEILLANCE_IMMUNITY.md · genes/worm/<gene>/