title: TiMEx: a waiting time model for mutually exclusive cancer alterations.
abstract: 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/TiMEx
  
  
  
  niko.beerenwinkel@bsse.ethz.ch
  
  
  
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zürich, Swiss Institute of Bioinformatics, Basel 4058, Switzerland and.
authors.forename: Simona
authors.initials: S
authors.lastname: Constantinescu
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zürich, Swiss Institute of Bioinformatics, Basel 4058, Switzerland and.
authors.forename: Ewa
authors.initials: E
authors.lastname: Szczurek
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zürich, Swiss Institute of Bioinformatics, Basel 4058, Switzerland and.
authors.forename: Pejman
authors.initials: P
authors.lastname: Mohammadi
authors.affiliation: Faculty of Statistics, Technische Universität Dortmund, Dortmund 44221, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Rahnenführer
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zürich, Swiss Institute of Bioinformatics, Basel 4058, Switzerland and.
authors.forename: Niko
authors.initials: N
authors.lastname: Beerenwinkel
mesh_terms: D000465:Algorithms; D023281:Genomics; D006801:Humans; D008962:Models, Theoretical; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D012984:Software