SASE-hunter

SASE-hunter identifies genomic loci with accelerated somatic mutation rates in cancer genomes, prioritizing non-coding regulatory regions that may contribute to oncogenesis.

Key Features:

• SASE detection: Identifies the Signature of Accelerated Somatic Evolution (SASE) as loci with significant excesses of somatic mutations.
• Non-coding focus: Targets SASE events particularly outside protein-coding regions, emphasizing regulatory loci.
• Multi-sample analysis: Compares somatic mutation patterns across multiple cancer samples to detect loci recurrent across patients.
• Dataset scale: Applied to 906 samples from 12 tumor types for discovery and validation of SASE loci.
• Nucleotide substitution patterns: Detects substitution spectra indicative of oxidative DNA damage and local somatic hypermutation.
• Prioritization: Ranks loci carrying SASE across multiple patients even when individual base-pair mutations are rare.
• Expression and clinical associations: Reports correlations between SASE loci and gene over-expression, age of cancer onset, disease aggressiveness, and patient survival.
• Promoter discoveries: Identified SASE in promoters of MYC, BCL2, RBM5, and WWOX.

Scientific Applications:

• Non-coding driver discovery: Identifying regulatory mutations outside coding regions that may drive oncogenesis.
• Functional prioritization: Prioritizing candidate regulatory loci for follow-up functional validation based on recurrence and mutation patterns.
• Clinical correlation: Linking SASE loci to gene expression changes and clinical parameters such as age of onset, aggressiveness, and survival.
• Pan-cancer comparison: Comparing SASE occurrence across tumor types using cohorts including 12 tumor types and 906 samples.

Methodology:

Performs comparative analysis of somatic mutation frequencies across samples (906 samples from 12 tumor types) to identify loci with excess mutations (SASE), characterizes nucleotide substitution patterns indicative of oxidative DNA damage and local somatic hypermutation, and prioritizes loci recurrent across patients.