Portal de Periódicos da CAPES

TiMEx: a waiting time model for mutually exclusive cancer alterations

2015; Oxford University Press; Volume: 32; Issue: 7 Linguagem: Inglês

10.1093/bioinformatics/btv400

1367-4811

Simona Constantinescu, Ewa Szczurek, Pejman Mohammadi, Jörg Rahnenführer, Niko Beerenwinkel,

Genomics and Chromatin Dynamics

Despite recent technological advances in genomic sciences, our understanding of cancer progression and its driving genetic alterations remains incomplete.We introduce TiMEx, a generative probabilistic model for detecting patterns of various degrees of mutual exclusivity across genetic alterations, which can indicate pathways involved in cancer progression. TiMEx explicitly accounts for the temporal interplay between the waiting times to alterations and the observation time. In simulation studies, we show that our model outperforms previous methods for detecting mutual exclusivity. On large-scale biological datasets, TiMEx identifies gene groups with strong functional biological relevance, while also proposing new candidates for biological validation. TiMEx possesses several advantages over previous methods, including a novel generative probabilistic model of tumorigenesis, direct estimation of the probability of mutual exclusivity interaction, computational efficiency and high sensitivity in detecting gene groups involving low-frequency alterations.TiMEx is available as a Bioconductor R package at www.bsse.ethz.ch/cbg/software/TiMExniko.beerenwinkel@bsse.ethz.chSupplementary data are available at Bioinformatics online.