Computational Prediction of Genetic Drivers in Cancer

Abstract

Cancer is a complex genetic disease driven by somatic mutations in the genomes of cancer cells. Distinguishing pathogenic ‘driver’ mutations from non‐pathogenic ‘passenger’ mutations is a central task for functionalising cancer genomics in patient care. With the outpouring of genomic information from next‐generation sequencing, predictive algorithms have become relevant to filter the outnumbered pathogenic driver mutations from non‐pathogenic passenger mutations. Computational approaches are available for predicting cancer drivers at mutation, gene and pathway levels. These algorithms use statistical approaches that have their advantages and drawbacks. The current trend is to use multiple and complementary methods for a more accurate prioritisation of cancer driver candidates available for targeted therapy at the clinical level.

Key Concepts

  • Cancer is a disease driven by mutations in the genome.
  • Only a small fraction of mutations are drivers that are responsible for cancer initiation and progression.
  • Distinguishing drivers from passengers is essential for genomic medicine.
  • Computational prediction of drivers is challenging due to the complexity of biology and genomics.
  • Statistical and machine learning approaches have been applied to discover the signature of drivers.
  • A mutation can affect the function of multiple genes and pathways.
  • The function of a mutation is context‐dependent and can vary in different diseases.

Keywords: cancer; driver; genomics; function; predictor; computational; mutation; tools; bioinformatics

Figure 1. An overview of three broader approaches for predicting potential candidate driver (mutations, genes and pathways) from somatic mutations.
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Djotsa Nono, Alice B, Chen, Ken, and Liu, Xiaoming(Feb 2016) Computational Prediction of Genetic Drivers in Cancer. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0025331]