Format

Send to:

Choose Destination
See comment in PubMed Commons below
Bioinformatics. 2013 Jun 15;29(12):1504-10. doi: 10.1093/bioinformatics/btt182. Epub 2013 Apr 25.

Predicting the functional consequences of cancer-associated amino acid substitutions.

Author information

  • 1Bristol Centre for Systems Biomedicine and MRC CAiTE Centre, School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK.

Abstract

MOTIVATION:

The number of missense mutations being identified in cancer genomes has greatly increased as a consequence of technological advances and the reduced cost of whole-genome/whole-exome sequencing methods. However, a high proportion of the amino acid substitutions detected in cancer genomes have little or no effect on tumour progression (passenger mutations). Therefore, accurate automated methods capable of discriminating between driver (cancer-promoting) and passenger mutations are becoming increasingly important. In our previous work, we developed the Functional Analysis through Hidden Markov Models (FATHMM) software and, using a model weighted for inherited disease mutations, observed improved performances over alternative computational prediction algorithms. Here, we describe an adaptation of our original algorithm that incorporates a cancer-specific model to potentiate the functional analysis of driver mutations.

RESULTS:

The performance of our algorithm was evaluated using two separate benchmarks. In our analysis, we observed improved performances when distinguishing between driver mutations and other germ line variants (both disease-causing and putatively neutral mutations). In addition, when discriminating between somatic driver and passenger mutations, we observed performances comparable with the leading computational prediction algorithms: SPF-Cancer and TransFIC.

AVAILABILITY AND IMPLEMENTATION:

A web-based implementation of our cancer-specific model, including a downloadable stand-alone package, is available at http://fathmm.biocompute.org.uk.

PMID:
23620363
[PubMed - indexed for MEDLINE]
PMCID:
PMC3673218
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk