Nemaline Myopathy Curation Interaction Summary
Date: 2026-02-19
Branch: nemaline_rod_myopathy
Deep Research Provider: Falcon
1. Primary Request and Intent
The user first asked for a tour of the dismech project (a LinkML-based disease pathophysiology knowledge base). After the walkthrough, the user invoked /curate nemaline rod myopathy to create a new disorder entry following the initiate-new-disorder-creation skill workflow.
After the initial curation was complete, the user challenged whether 7 specific foundational papers were considered during curation — they were not, as the falcon deep research provider focused on 2023–2024 literature. The user then requested incorporation of those 7 papers into the entry, covering the full historical breadth of NM literature from 1984 to 2024.
2. Key Technical Concepts
- LinkML schema validation: Disorder YAML files must conform to the
Diseaseclass insrc/dismech/schema/dismech.yaml - Three-layer validation stack: schema validation (
just validate), ontology term validation (just validate-terms), and reference/snippet validation (just validate-references) - Evidence-backed curation: Every factual claim requires a PMID reference with an exact quoted snippet from the abstract — no paraphrasing allowed
- Ontology term bindings: Phenotypes → HPO, Cell types → CL, Biological processes → GO, Treatments → MAXO, Diseases → MONDO
- OAK (Ontology Access Kit): Used for looking up ontology terms via
uv run runoak -i sqlite:obo:<ontology> info - Deep research via falcon:
just research-disorder falcon Nemaline_Myopathyruns external deep research and outputs toresearch/Nemaline_Myopathy-deep-research-falcon.md - Reference fetching:
just fetch-reference PMID:nnnnnorjust fetch-reference DOI:...caches abstracts toreferences_cache/ - Pre-write validation hook: A git hook at
.claude/hooks/validate_disorder_hook.pyblocks writes that would create invalid YAML files - Compliance scoring:
just compliancereports coverage percentages for evidence, terms, and other recommended fields
3. Workflow Steps
Step 1: Verify Disorder Doesn't Exist
- Checked
kb/disorders/— no existing Nemaline Myopathy file found - Looked up MONDO term:
MONDO:0018958(nemaline myopathy)
Step 2: Create Initial YAML Scaffold
- Created
kb/disorders/Nemaline_Myopathy.yamlwith textbook knowledge - Included basic structure: name, category (Mendelian), description, disease_term, parents, subtypes, pathophysiology, phenotypes, genetics, treatments
Step 3: Deep Research
- Ran
just research-disorder falcon Nemaline_Myopathy - Research output written to
research/Nemaline_Myopathy-deep-research-falcon.md - Falcon returned 42 citations focused on 2023–2024 literature
- Key limitation: falcon's recency bias missed foundational/classic NM papers
Step 4: DOI-to-PMID Resolution
- Falcon output provided DOIs rather than PMIDs
- NCBI PMC ID converter API returned 404 errors for all DOIs
- Solved by using Biopython
Entrez.esearchto search PubMed by title keywords - Successfully resolved 10 DOIs to correct PMIDs
Step 5: Evidence Enhancement
- Fetched and read 10 abstracts from falcon research
- Added exact snippet quotes from abstracts to evidence items
- Added ontology terms (HP, CL, GO, MAXO) via OAK lookups
Step 6: User-Identified Paper Incorporation
- User identified 7 foundational papers not covered by falcon research:
- PMID:17272906 — Indian cohort study (2007)
- PMID:31228046 — Comprehensive NM review (2019)
- PMID:9372751 — Adult-onset NM case report (1998)
- PMID:35810298 — Severe ACTA1-NM study (2022)
- PMID:6481414 — Early adult NM report with mixed pathology (1984)
- PMID:19208402 — NM with isolated respiratory failure (2009)
- PMID:39691005 — SLONM case with monoclonal protein (2024)
- All 7 papers were fetched, read, and incorporated with exact snippets across multiple sections
Step 7: Validation
just validate— schema validation passedjust validate-terms-file— ontology term validation passedjust validate-references— reference/snippet validation passedjust compliance— 82.4% compliance (82.8% weighted)
4. Files Created/Modified
| File | Action | Description |
|---|---|---|
kb/disorders/Nemaline_Myopathy.yaml |
Created | Main disorder entry (711 lines) |
research/Nemaline_Myopathy-deep-research-falcon.md |
Generated | Falcon deep research output |
pages/disorders/Nemaline_Myopathy.html |
Generated | Rendered HTML page |
references_cache/PMID_38634969.md |
Fetched | Karimi 2024 — NEB thin filament mechanisms |
references_cache/PMID_36703211.md |
Fetched | Nicolau 2023 — Nemaline rod signatures (iNM vs SLONM) |
references_cache/PMID_38376469.md |
Fetched | Galli 2024 — Tirasemtiv in NEM3 mouse model |
references_cache/PMID_36661122.md |
Fetched | Casey 2023 — NRAP in nebulin-deficient NM |
references_cache/PMID_36960434.md |
Fetched | 2023 — Pediatric NM systematic review |
references_cache/PMID_36714460.md |
Fetched | Moreno 2023 — NEB-NM cohort (33 patients) |
references_cache/PMID_39651462.md |
Fetched | van Kleef 2024 — NEM6/KBTBD13 (24 patients) |
references_cache/PMID_37432316.md |
Fetched | Mansur 2023 — KLHL40/UPS mechanism |
references_cache/PMID_38500810.md |
Fetched | 2024 — ACTA1 case report |
references_cache/PMID_39501809.md |
Fetched | 2024 — Additional NM reference |
references_cache/PMID_17272906.md |
Fetched | Jain 2007 — Indian NM cohort |
references_cache/PMID_31228046.md |
Fetched | Ravenscroft 2019 — Authoritative NM review |
references_cache/PMID_9372751.md |
Fetched | Gyure 1997 — Adult-onset NM with HIV |
references_cache/PMID_35810298.md |
Fetched | Néstor-Bergmann 2022 — Severe ACTA1-NM |
references_cache/PMID_6481414.md |
Fetched | Engel 1984 — Early adult NM report |
references_cache/PMID_19208402.md |
Fetched | Kelly 2009 — NM respiratory failure |
references_cache/PMID_39691005.md |
Fetched | Vashisht 2024 — SLONM case |
5. Errors and Fixes
Schema Validation Errors (caught by pre-write hook)
| Error | Root Cause | Fix |
|---|---|---|
description not allowed in Genetic class |
Schema uses notes for Genetic, not description |
Changed all description: to notes: in genetic entries |
notes not allowed in Inheritance class |
Overcorrection from previous error; schema allows description here |
Changed back to description: in inheritance entries |
percentage and population not valid in EpidemiologyInfo |
Used Prevalence-style fields not in schema | Restructured to name: Incidence with description and notes |
| Snippet validation failure for PMID:39651462 | Brackets [4.9-8.1] in snippet may have caused matching issues |
Replaced with different snippet from same abstract |
DOI Resolution Errors
| Error | Root Cause | Fix |
|---|---|---|
| NCBI PMC ID converter API 404 | API endpoint returned 404 for all DOIs | Used Biopython Entrez.esearch with title keywords |
| Guessed PMIDs were wrong | Manual PMID guessing returned unrelated papers (neurofilaments, breast cancer, scorpion venom) | Abandoned guessing; used systematic title-based search |
Deep Research Limitation
| Issue | Impact | Mitigation |
|---|---|---|
| Falcon provider focused on 2023–2024 | Missed 7 foundational papers (1984–2022) | User identified gaps; papers manually incorporated |
6. Final Entry Statistics
| Metric | Value |
|---|---|
| Subtypes | 5 (Severe Congenital, Typical Congenital, Childhood-Onset, Adult-Onset, NEM6) |
| Pathophysiology mechanisms | 6 (Thin Filament Dysfunction, Nemaline Rod Formation, Thin Filament Length Dysregulation, UPS/KLHL40, Nuclear Envelope Disruption, NRAP-Mediated Sarcomere Disorganization) |
| Phenotypes | 9 |
| Genetic entries | 10 (NEB, ACTA1, KBTBD13, KLHL40, TPM3, TPM2, TNNT1, CFL2, LMOD3, KLHL41) |
| Treatments | 7 (including 2 investigational) |
| Epidemiology entries | 1 |
| Unique PMIDs | 17 (spanning 1984–2024) |
| Compliance | 82.4% (82.8% weighted) |
| Validation | All 3 layers pass (schema, terms, references) |
7. PMIDs Used
| PMID | First Author | Year | Key Contribution |
|---|---|---|---|
| 38634969 | Karimi | 2024 | NEB thin filament length mechanisms, omecamtiv mecarbil |
| 36703211 | Nicolau | 2023 | Rod signatures: iNM vs SLONM |
| 38376469 | Galli | 2024 | Tirasemtiv in NEM3 mouse model |
| 36661122 | Casey | 2023 | NRAP as disease modifier in NEB-NM |
| 36960434 | — | 2023 | Pediatric NM systematic review |
| 36714460 | Moreno | 2023 | NEB-NM cohort (33 patients) |
| 39651462 | van Kleef | 2024 | NEM6/KBTBD13 cross-sectional study (24 patients) |
| 37432316 | Mansur | 2023 | KLHL40/UPS/ER-Golgi trafficking mechanism |
| 38500810 | — | 2024 | Novel ACTA1 variant case report |
| 39501809 | — | 2024 | Additional NM reference |
| 17272906 | Jain | 2007 | Indian NM cohort, epidemiology (0.53% of muscle diseases) |
| 31228046 | Ravenscroft | 2019 | Comprehensive NM review (authoritative) |
| 9372751 | Gyure | 1997 | Adult-onset NM with HIV, rod morphology description |
| 35810298 | Néstor-Bergmann | 2022 | Severe ACTA1-NM, nuclear envelope disruption |
| 6481414 | Engel | 1984 | Early adult NM case, mixed pathology |
| 19208402 | Kelly | 2009 | NM with isolated respiratory failure |
| 39691005 | Vashisht | 2024 | SLONM case with monoclonal protein |
8. Lessons Learned
-
Deep research providers have recency bias: Falcon focused on 2023–2024 papers, missing foundational literature. Supplementary manual reference searching is needed, especially for well-established diseases with decades of published literature.
-
Schema field constraints vary by class: Different LinkML classes (
Genetic,Inheritance,EpidemiologyInfo) have different allowed slots. Always check the schema before writing YAML. -
DOI-to-PMID resolution is fragile: The NCBI PMC ID converter API can fail. Title-based PubMed search via Biopython
Entrez.esearchis a reliable fallback. -
Never guess PMIDs: Attempting to guess PMIDs based on author/year produces completely unrelated papers. Always use systematic search.
-
Pre-write validation hooks catch errors early: The
.claude/hooks/validate_disorder_hook.pyhook prevented multiple schema-invalid writes from being saved, forcing immediate correction. -
Snippet bracket characters can cause validation issues: Brackets in quoted snippets (e.g.,
[4.9-8.1]) may not survive the reference validation pipeline. Use alternative snippets when possible.
9. User Messages (Chronological)
- "Give me a tour of the dismech project"
/curate nemaline rod myopathy- "is there evidence in the output, that you considered and read these papers: https://pubmed.ncbi.nlm.nih.gov/17272906/ https://pubmed.ncbi.nlm.nih.gov/31228046/ https://pubmed.ncbi.nlm.nih.gov/9372751/ https://pubmed.ncbi.nlm.nih.gov/35810298/ https://pubmed.ncbi.nlm.nih.gov/6481414/ https://pubmed.ncbi.nlm.nih.gov/19208402/ https://pubmed.ncbi.nlm.nih.gov/39691005/"
- "yes" (confirming to incorporate the 7 papers)
- "write out this interaction to a md file"