Co Scientist Rare Disease Genetics

Rare disease genetics

Rare disease genetics skill. Rare variant prioritization, exome/genome sequencing analysis, phenotype-driven gene ranking, and diagnostic yield optimization.

Use This Skill When

• Rare variant prioritization.
• Exome/genome sequencing analysis.
• Phenotype-driven gene ranking.
• Diagnostic yield optimization.

Required Inputs

• Research objective, decision target, or hypothesis.
• Available data, source constraints, and domain assumptions.
• Required outputs, success metrics, and deadline or reproducibility constraints.

Workflow

1. Confirm scope, assumptions, and the exact artifact set to save.
2. Apply the narrowest domain method that answers the request with defensible evidence.
3. Save code, tables, figures, and intermediate outputs to files instead of chat-only output.
4. State limitations, uncertainty, and any validation or sensitivity checks performed.
5. Append skill selection, handoff I/O, and file writes to logs/process-log.jsonl.

Deliverables

• report.md: concise method, results, interpretation, and file inventory in the user's language.
• results/: structured outputs, metrics, model artifacts, or extracted findings.
• figures/: English-only charts, diagrams, or panels when visual output is needed.
• data/: processed or derived datasets when transformation occurs.

Available Tools (MCP)

External tools available via ToolUniverse MCP server. Falls back to Python requests + public REST APIs when MCP is unavailable.

Quality Gates

• The selected method matches the scientific question and stated assumptions.
• Outputs are reproducible, saved to files, and traceable from inputs to conclusions.
• Missing data, uncertainty, bias, and hard limits are made explicit.
• report.md and logs/process-log.jsonl reference the generated artifacts.
• No essential result remains chat-only.

If any gate fails: identify the specific failing check, fix the issue, and re-validate before proceeding.

Gotchas

• Reference genome version (hg19 vs hg38) must be confirmed before analysis. Mixing versions produces invalid coordinates
• FASTQ quality scores can use different encoding (Phred+33 vs Phred+64). Verify encoding before alignment
• Batch effects between sequencing runs must be assessed. Combine technical replicates only after batch correction

Validation Loop

1. Execute analysis and generate outputs
2. Check:
   • Method selection matches the research question and stated assumptions
   • All outputs are saved to files (no chat-only results)
   • Limitations and uncertainty are explicitly stated
   • logs/process-log.jsonl is updated with execution trace
3. If any check fails:
   • Identify the failing gate
   • Fix the specific issue
   • Re-run validation
4. Proceed only after all gates pass