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sergeeeysergeeey/Claude-cod-top-2026/skills/extensions/archcode-genomics/SKILL.md

archcode-genomics

Skill9 starsChanged 6 months agoMITView on GitHub

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  1. Distinctive:

    USE when working with genomic data, variant analysis, or chromatin structure.

    line 12

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SKILL.md
<!-- BSV — Brief Skill View | поиск: BSV Скил : archcode-genomics TL;DR : Патогенность геномных вариантов (биоинформатика) Вызов : 'геномный анализ', 'archcode' НЕ для : Клинические решения -->

name: archcode-genomics description: > [STATUS: review] [CONFIDENCE: high] [REVIEWED: 2026-03-13] USE when working with genomic data, variant analysis, or chromatin structure. Triggers: ClinVar, chromatin, variant, extrusion, loop, locus, HBB, SpliceAI, pathogenicity, genomics, ARCHCODE, structural variant, pearl. paths: "/variant,/vcf,/clinvar,/extrusion,**/chromatin" effort: max

ARCHCODE Genomics Skill

Project Context

ARCHCODE is a physics-based method for predicting pathogenicity of non-coding variants through simulation of chromatin loop extrusion. It detects "pearl variants" — variants invisible to sequence-based methods (VEP, CADD, SpliceAI).

Key Data

  • 9 validated loci: HBB, HBA, BCL11A, CTCF-rich, GATA1, beta-globin LCR, SHH-ZRS, SOX9-KCNJ, MYC-TAD
  • # YOUR_VARIANT_COUNT ClinVar variants analyzed
  • # YOUR_PEARL_COUNT pearl variants detected (pathogenic, invisible to VEP/SpliceAI)

Pearl Variant — Definition

A variant that:

  1. VEP = benign/modifier (not pathogenic)
  2. SpliceAI delta = 0 (no splicing effect)
  3. MPRA enrichment = null (no functional data)
  4. BUT: disrupts 3D chromatin structure (CTCF binding, loop anchor, TAD boundary)

Pipeline

ClinVar VCF → VEP annotation → SpliceAI filtering →
ARCHCODE simulation (loop extrusion) →
Structural impact scoring → Pearl detection

Competitors (for Discussion section)

  • ncVarPred-1D3D (PMID 37669132) — sequence + 3D, but without ClinVar pearl detection
  • PRISMR (PMID 29662163) — polymer modeling, but without clinical validation
  • Sei — sequence-only, does not see structural blind spots

MCP Servers

Switch to SCIENCE profile: switch-profile.ps1 science

  • ncbi-datasets: gene info, sequences
  • uniprot: protein features, variants, domains
  • pubmed-mcp: literature search

Gotchas

  • VEP/CADD miss non-coding variants — always check 3D chromatin context
  • Pearl variants require loop extrusion simulation — sequence-only methods fail

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