cyberneticlibrary

Research disease mechanisms with genomics

disease-researchskillsetup L235
ammawla/encode-toolkit
What it does

Connect GWAS variants to ENCODE regulatory elements for disease mechanism discovery

Best for

Disease mechanism research where non-coding variants need interpretation, or identifying therapeutic targets from epigenomic evidence rather than coding-only databases.

Inputs
  • · GWAS variant list (SNPs, effect sizes)
  • · disease/trait phenotype
  • · disease-relevant tissue(s)
Outputs
  • · variant-to-cCRE mapping
  • · enrichment statistics (S-LDSC heritability partition)
  • · drug target candidates (Open Targets integration)
Requires
  • · ENCODE (926,535 cCREs)
  • · GWAS Catalog
  • · Open Targets Platform
  • · SCREEN portal
  • · ClinicalTrials.gov
  • · PubMed
Preconditions

90% of disease variants are non-coding; correct tissue selection critical (disease-tissue-mapping table required)

Failure modes
  • · wrong tissue chosen → regulatory elements miss disease mechanism
  • · heritability enrichment inverted if control regions misspecified
  • · drug target not druggable (no chemical matter) → false positive
Trust signals
  • · Maurano et al. 2012 cited (76.6% GWAS SNPs in DNase hotspots)
  • · S-LDSC partitioning (Finucane 2015)
  • · ABC model for enhancer-gene links (Nasser 2021)