MORFEE

MORFEE annotates single-nucleotide variants in 5' untranslated regions (5' UTRs) that create upstream AUGs (uAUGs) and upstream open reading frames (uORFs) to assess their potential impact on translation and gene expression.

Key Features:

• Target variants: Detects single nucleotide variants in 5' UTR sequences that create upstream translation initiation AUG codons (uAUGs) leading to uORFs.
• Input format: Operates on variant call format (VCF) files for genomic variant representation.
• Annotation of uORFs: Annotates resulting upstream open reading frames and their positional relationship to canonical coding sequences.
• Premature stop detection: Identifies uORFs that introduce premature stop codons within the 5' UTR-derived reading frames.
• Impact prediction: Predicts potential functional effects of uORF-creating variants on translation and gene expression.
• Implementation: Provided as an R package for computational analysis.

Scientific Applications:

• GWAS interpretation: Helps explain statistical association signals by identifying 5' UTR variants that may have functional consequences via uORF creation.
• Rare disease variant discovery: Identifies candidate non-coding variants that could underlie rare disease forms through altered translation initiation.
• Gene regulation studies: Enables investigation of how uORFs compete with canonical proteins for ribosomal machinery and affect gene expression.
• Non-coding variant annotation: Provides complementary annotation for studies focused beyond coding-region variants.

Methodology:

Analyzes VCF files to detect SNVs in 5' UTRs that create upstream AUG codons, annotates resulting uORFs and potential premature stop codons, and predicts their impact on translation and gene expression.