MuSiCal

MuSiCal provides a rigorous analytical framework with algorithms that solve major problems in mutational signature discovery and assignment, outperforming state-of-the-art methods to enable enhanced understanding of mutational forces driving tumorigenesis.

Key Features:

• Signature Discovery: MuSiCal improves the discovery of new mutational signatures, including nine indel signatures absent in the current catalog.
• Signature Assignment: MuSiCal assigns proper weights to existing signatures with greater accuracy and sensitivity than state-of-the-art algorithms.
• Ambiguous Signature Resolution: MuSiCal resolves long-standing issues with ambiguous 'flat' signatures.
• Improved Catalog Generation: MuSiCal produces an improved catalog of signatures and their assignments by reanalyzing more than 2,700 cancer genomes.

Scientific Applications:

• Cancer Genomics: MuSiCal enhances understanding of mutational forces driving tumorigenesis through analysis of somatic mutations in cancer genomes.
• Clinical Informatics: MuSiCal advances the potential of mutational signature analysis to inform prognosis and treatment decisions by addressing methodological challenges that hinder broader clinical applications.
• Etiological Investigation: MuSiCal provides insights into signatures with unknown etiologies.

Methodology:

MuSiCal employs algorithms for signature discovery and assignment validated through simulation studies; the framework was applied to reanalyze more than 2,700 cancer genomes to generate an improved catalog of signatures.