Remus

Remus prioritizes regulatory regions and variants associated with monogenic diseases to facilitate identification of pathogenic noncoding alterations in disease-relevant tissues.

Key Features:

• Integration of comprehensive databases: Leverages tissue-specific regulatory loci from ENCODE and FANTOM and miRNA–gene interactions from miRTarBase and miRWalk to map regulatory regions relevant to specific phenotypes.
• Tissue-specific analysis: Filters regulatory features and variants by activity status in tissues affected by the disorder, reducing the number of considered variants by 82.5% versus tissue-agnostic searches.
• Evaluation on curated pathogenic mutations: In an assessment of 146 regulatory mutations across 68 monogenic disorders, the regulator containing the pathogenic mutation was identified in 89.7% of cases.

Scientific Applications:

• Regulatory variant prioritization: Prioritizes noncoding regulatory variants for follow-up in genetic studies of monogenic diseases.
• Complementing coding variant analysis: Supplements analyses of coding variation by highlighting tissue-relevant regulatory elements linked to disease-associated genes.
• Genomic diagnostic support: Enhances interpretation of whole-genome sequencing experiments by narrowing candidate noncoding variants in disease-relevant tissues.

Methodology:

Systematic search for regulatory features linked to known disease-associated genes, using curated data on tissues affected by specific disorders and filtering variants by tissue relevance.