SNPnotes

SNPnotes annotates and prioritizes functional variants in the non-coding genome using tissue-specific regulatory data and clinical and GWAS knowledge for whole-genome sequencing (WGS)-based research and diagnostics.

Key Features:

• Tissue-Specific Annotation: Prioritizes variants using user-defined tissue-specific epigenetic maps and genome regulation maps, including application with 12 gut-specific eQTL maps.
• Integration of Multiple Data Sources: Integrates ClinVar, GTEx, and the NHGRI-EBI GWAS catalogue to combine clinical pathogenicity, tissue-specific gene regulation, and disease-association evidence.
• Non-coding Variant Prioritization: Targets functional variants in the non-coding genome by leveraging open chromatin data, gene expression modulation (eQTLs), and GWAS literature.
• High-Throughput Processing: Processes large-scale variant sets (demonstrated on over 6 million SNPs) to identify high-priority variants overlapping genes with known pathogenicity and disease associations.
• WGS-Compatible Input: Accepts variant calls derived from whole-genome sequencing (WGS) for clinical and research analyses.
• Customization and Flexibility: Permits software-level modifications to tailor the pipeline and tissue-specific annotation maps for diverse biomedical applications.

Scientific Applications:

• Clinical WGS Variant Prioritization: Supports prioritization of WGS-derived variants for diagnostic interpretation by emphasizing tissue-relevant and clinically associated variants.
• Mechanistic Hypothesis Generation: Facilitates generation of hypotheses about mechanisms driving tissue-specific clinical symptoms by focusing on variants that modulate gene expression and have GWAS or ClinVar associations.
• Disease-Specific Investigation: Enables investigation of gastrointestinal and metabolic disorder genetics using gut-specific eQTL maps and GWAS associations.

Methodology:

Input variant calls from patient data; prioritize variants using integrated databases such as ClinVar, GTEx, and the NHGRI-EBI GWAS catalogue; and focus on tissue-specific regulatory elements and eQTL maps to rank variants.