/claw-methylation-cycle

name: claw-methylation-cycle
license: MIT
metadata:
  openclaw:
    requires:
      bins:
      - python3
      env: null
      config: null
    always: false
    emoji: 🧬
    homepage: https://github.com/ClawBio/ClawBio
    os:
    - darwin
    - linux
    install: 'pip install -e .

      '
    trigger_keywords:
    - methylation
    - MTHFR
    - folate cycle
    - BH4
    - homocysteine
    - methylation cycle
    - metilación
    - neurotransmitter synthesis
  author: Samuel Carmona Aguirre <samuel@unimed-consulting.es>
  demo_data_path: demo_input.txt
  dependencies_python: '>=3.9'
  guideline_doi: 10.3390/nu13030768
  input_format: 23andme, adntro, ancestry
  output_format: markdown, json
  tags:
  - genomics
  - methylation
  - MTHFR
  - neurodevelopment
  trigger_keywords:
  - methylation
  - MTHFR
  - folate cycle
  - BH4
  - homocysteine
  - methylation cycle
  - metilación
  - neurotransmitter synthesis
  validation_tier: community
  version: 0.1.3
description: Methylation cycle analysis — enzymatic activity profiles, Net Methylation Capacity, BH4 axis estimates, compound heterozygosity detection from SNP genotype data.

claw-methylation-cycle

Methylation cycle analysis skill for ClawBio. Produces enzymatic activity profiles, Net Methylation Capacity (NMC), BH4 axis estimates, compound heterozygosity detection, and clinician-review genotype findings from raw SNP genotype data.

---

Trigger

**Fire this skill when:**

• The user asks about methylation, MTHFR variants, folate cycle, or

homocysteine risk from a genotype file.

• A raw SNP file (23andMe / ADNTRO / Ancestry format) is provided and the

clinical question involves methylation, BH4, dopamine/serotonin synthesis capacity, or neurodevelopmental contexts (ADHD, depression, anxiety).

• The upstream workflow (PharmGx Reporter, NutriGx Advisor) has flagged

MTHFR or MTRR and the clinician needs the full methylation panel.

• Keywords present: `methylation`, `MTHFR`, `BH4`, `folate cycle`,

`metilación`, `ciclo de metilación`, `homocysteine`, `5-MTHF`, `methylcobalamin`, `neurotransmitter synthesis`, `dopamine upstream`.

**Do NOT fire this skill when:**

• The question is purely about folic acid supplementation without a genotype file.
• The user is asking about MTHFR in the context of thrombophilia/clotting

only — use PharmGx Reporter for warfarin/anticoagulation questions.

• Only N-GENE polygenic risk data is available (no raw SNP file) — this skill

requires genotype-level input; PRS percentiles are not sufficient.

• The SNP file format is VCF, FASTQ, BAM, or PLINK binary — these require

preprocessing before this skill can run.

• The clinical question is exclusively pharmacogenomic (CYP enzymes) — use

PharmGx Reporter instead.

---

Workflow

1. **Receive input** — Accept either a raw genotype file path or a pre-parsed `snp_dict`. If a file is provided, call `parse_genotype_file()` to extract the rsID → genotype mapping.

2. **Panel coverage check** — Compare detected rsIDs against the 9-gene methylation panel. Log missing SNPs. For any SNP absent from the input, mark the corresponding gene as `not_assessed` — do NOT silently assume normal activity (Safety Rule 6).

3. **Enzymatic activity scoring** — For each gene, map the diplotype to an estimated activity percentage. Heterozygous risk variants reduce activity by their assigned weight; homozygous variants apply the full reduction.

4. **Compound heterozygosity detection** — Check MTHFR C677T (rs1801133) and A1298C (rs1801131) simultaneously. If both are heterozygous, set `compound_heterozygosity = True` and apply the combined activity reduction (~15% of normal — more severe than either variant alone).

5. **Net Methylation Capacity (NMC)** — Compute the weighted average of all enzyme activities. Clamp to [0, 100]. Expose `coverage_pct` and `snps_missing`; flag NMC as partial if key SNPs are absent.

6. **BH4 axis capacity** — Derive BH4 from MTHFR activity and MTRR modifier. Report clinical implications for dopamine and serotonin synthesis in neurodevelopmental presentations.

7. **Prioritised recommendations** — Generate PRIORITY 1 / 2 / 3 recommendations based on active findings. Lead with highest clinical impact (compound het MTHFR or severely reduced BH4).

8. **Output** — Write `report.md` (human-readable) and `result.json` (structured, for downstream integration).

---

Example Output

╔══════════════════════════════════════════════════════════════╗
║  ClawBio · Methylation Cycle Analysis Report                 ║
║  Author: Samuel Carmona Aguirre · RUO — Not a medical device ║
╚══════════════════════════════════════════════════════════════╝

Executive Summary
─────────────────
Net Methylation Capacity : 53 / 100  🔴 Reduced
BH4 Axis Capacity        : 31 / 100  🔴 Reduced
MTHFR Compound Het.      : YES ⚠️   (C677T + A1298C)
Dopamine Synthesis       : Severely Reduced
Serotonin Synthesis      : Severely Reduced

Enzymatic Activity Profile
──────────────────────────
Gene    Activity  Status                Key Variants
MTHFR    15%     🔴 Severely reduced   C677T, A1298C
MTRR     60%     🟡 Moderately reduced A66G
MTR     100%     🟢 Normal             –
CBS     100%     🟢 Normal             –
BHMT     40%     🔴 Moderately reduced R239Q
SHMT1    80%     🟢 Mildly reduced     C1420T
COMT     55%     🟡 Moderately reduced Val158Met
AHCY    100%     🟢 Normal             –

Clinical Recommendations — FOR CLINICIAN REVIEW ONLY
──────────────────────────────────────────────────────
⚠️  The following is genotype-based information for qualified clinician use.
    Do not self-administer. All nutrients listed are reported in the peer-reviewed
    literature for the pathways indicated; dosing and indication require
    individualised clinical assessment.

Genotype findings:
  • 5-MTHF (methylfolate) preferred over synthetic folic acid (MTHFR C677T/A1298C).
    Ref: Lamers Y et al. (20