Session 5: Mutational Signatures

Lecture

  • Types of signatures, flat signatures, endogenous/exogenous processes, mSigPortal, Kataegis
  • De novo identification of mutational signatures
  • Signature decomposition based on known reference signatures
  • Emerging mutational signatures in cancer genomic studies
  • Downstream analysis for mutational signature data

Practical

  • Mutational signature analysis using SigProfiler
  • De-novo analysis using SigProfilerExtractor
  • Explore mutational signatures data portals (mSigPortal, Signal, COSMIC)
  • Explore reference signatures in mSigPortal (mSigPortal Catalog)

In this session we will provide a comprehensive overview of mutational signatures as well as the methods to study them. We will begin by highlighting the history and concepts for mutational signatures. Most importantly, we will emphasize the findings of emerging mutational signature analyses used in cancer genomic studies to elucidate cancer etiology. Then we will introduce the algorithms, databases, and web portals for deciphering mutational signatures in cancer genomic studies, including de-novo extraction, decomposition to known reference signatures, analysis of clustered mutational signatures, topography analysis of mutational signatures, and evolution of mutational signatures within tumors. Finally, we will also show a few common experimental methods for validation of mutational signatures.

In the practical section, we will provide a tutorial to comprehensively study mutational signatures using web-based data portals. This tutorial will cover most of the basic knowledge of mutational signatures introduced in the lecture. In addition, we will also practice deciphering mutational signatures from example datasets. This practice will show how to perform de-novo and reference-based decomposition of mutational signatures using state-of-the-art algorithms.