SBSA: an online service for somatic binding sequence annotation.

Area of Science:

• Genomics
• Bioinformatics
• Molecular Biology

Background:

• Efficient annotation of altered binding sequences is crucial for understanding molecular mechanisms and developing therapeutic strategies.
• Existing tools have limitations in supporting diverse genomic variants and molecular regulators.

Purpose of the Study:

• To develop Somatic Binding Sequence Annotator (SBSA), a comprehensive online tool for annotating altered binding motifs/sequences.
• To support a wide range of genomic variants (e.g., somatic mutations, SNPs, RNA editing) and molecular regulators (e.g., TFs, RNA-binding proteins, miRNA targets).

Main Methods:

• SBSA supports diverse genomic variants and molecular regulators, including miRNA seeds and miRNA-mRNA 3'-UTR binding targets.
• The tool implements a personalized genome approach for joint adjacent variants and supports numerous species.
• Annotation of multi-omics data from over 30,890 human subjects was performed.

Main Results:

• Millions of somatic binding sequences were identified, including significant ones with known biological impacts.
• A somatic mutation in the TERT promoter region, creating a novel binding site for ETS1, was identified.
• The functional impact of the TERT mutation was experimentally validated in cancer cells.

Conclusions:

• SBSA is a powerful and versatile tool for annotating altered binding sequences across various genomic contexts and molecular regulators.
• The identified TERT promoter mutation and its functional consequence highlight SBSA's utility in discovering disease mechanisms.