title: A Dual Model for Prioritizing Cancer Mutations in the Non-coding Genome Based on Germline and Somatic Events.
abstract: We address here the issue of prioritizing non-coding mutations in the tumoral genome. To this aim, we created two independent computational models. The first (germline) model estimates purifying selection based on population SNP data. The second (somatic) model estimates tumor mutation density based on whole genome tumor sequencing. We show that each model reflects a different set of constraints acting either on the normal or tumor genome, and we identify the specific genome features that most contribute to these constraints. Importantly, we show that the somatic mutation model carries independent functional information that can be used to narrow down the non-coding regions that may be relevant to cancer progression. On this basis, we identify positions in non-coding RNAs and the non-coding parts of mRNAs that are both under purifying selection in the germline and protected from mutation in tumors, thus introducing a new strategy for future detection of cancer driver elements in the expressed non-coding genome.
authors.affiliation: Institute for Integrative Biology of the Cell, CNRS, CEA, Université Paris-Sud, Gif-sur-Yvette, France.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Laboratoire de Mathématique, Université Paris-Sud, Paris, France.
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Poursat
authors.affiliation: Service de Biostatistique et d'Epidémiologie, Gustave Roussy, Villejuif, France.|INSERM U1018, CESP, Université Paris-Sud, Villejuif, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Drubay
authors.affiliation: Institute for Integrative Biology of the Cell, CNRS, CEA, Université Paris-Sud, Gif-sur-Yvette, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Motz
authors.affiliation: RNA, epigenetics and genome fluidity, Institut Curie, PSL Research University, CNRS UMR3244, Université Pierre et Marie Curie, Paris, France.
authors.forename: Zohra
authors.initials: Z
authors.lastname: Saci
authors.affiliation: RNA, epigenetics and genome fluidity, Institut Curie, PSL Research University, CNRS UMR3244, Université Pierre et Marie Curie, Paris, France.
authors.forename: Antonin
authors.initials: A
authors.lastname: Morillon
authors.affiliation: Service de Biostatistique et d'Epidémiologie, Gustave Roussy, Villejuif, France.|INSERM U1018, CESP, Université Paris-Sud, Villejuif, France.
authors.forename: Stefan
authors.initials: S
authors.lastname: Michiels
authors.affiliation: Institute for Integrative Biology of the Cell, CNRS, CEA, Université Paris-Sud, Gif-sur-Yvette, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gautheret
mesh_terms: D019295:Computational Biology / Q000379:methods*; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D022661:RNA, Untranslated / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D022661:RNA, Untranslated