GREEN-DB

GREEN-DB provides annotation and prioritization of non-coding regulatory variants from whole-genome sequencing to support interpretation of regulatory elements, controlled genes, tissue activity, and disease relevance.

Key Features:

• Extensive Regulatory Element Collection: GREEN-DB catalogs approximately 2.4 million human regulatory regions annotated with controlled genes, tissues of activity, and associated phenotypes where available.
• Integration of Regulatory Information: The framework integrates regulatory element annotations with prediction scores and Human Phenotype Ontology (HPO)-based prioritization to enable systematic annotation of non-coding variants.
• Variation Constraint Metric: GREEN-DB includes a variation constraint metric that identifies regulatory regions under evolutionary constraint and associates these regions with disease-associated genes and essential genes from mouse knock-out screens.
• Non-Coding Impact Prediction Scores Comparison: The resource evaluates 19 non-coding impact prediction scores to guide prioritization of variants based on predicted regulatory effects.
• VCF Annotation Tool (GREEN-VARAN): GREEN-VARAN annotates variants in Variant Call Format (VCF) files with the framework's regulatory annotations and prioritization metrics.

Scientific Applications:

• Capture of disease-associated non-coding variants: GREEN-DB enables identification and capture of previously published disease-associated non-coding variants.
• Candidate gene discovery in WGS trios: The framework supports identification of additional candidate disease genes through whole-genome sequencing trio analyses by integrating regulatory annotations and HPO-based prioritization.
• Study of regulatory contributions to complex disease: GREEN-DB facilitates linking regulatory regions to phenotypes to investigate the genetic underpinnings of complex diseases.

Methodology:

Curation of a large regulatory-element database, calculation of variation constraint metrics, comparison of non-coding impact prediction scores, and development of the GREEN-VARAN VCF annotation tool.