title: Learning smoothing models of copy number profiles using breakpoint annotations.
abstract: BACKGROUND
  Many models have been proposed to detect copy number alterations in chromosomal copy number profiles, but it is usually not obvious to decide which is most effective for a given data set. Furthermore, most methods have a smoothing parameter that determines the number of breakpoints and must be chosen using various heuristics.
  
  
  RESULTS
  We present three contributions for copy number profile smoothing model selection. First, we propose to select the model and degree of smoothness that maximizes agreement with visual breakpoint region annotations. Second, we develop cross-validation procedures to estimate the error of the trained models. Third, we apply these methods to compare 17 smoothing models on a new database of 575 annotated neuroblastoma copy number profiles, which we make available as a public benchmark for testing new algorithms.
  
  
  CONCLUSIONS
  Whereas previous studies have been qualitative or limited to simulated data, our annotation-guided approach is quantitative and suggests which algorithms are fastest and most accurate in practice on real data. In the neuroblastoma data, the equivalent pelt.n and cghseg.k methods were the best breakpoint detectors, and exhibited reasonable computation times.
authors.affiliation: INRIA Sierra Project-Team, Paris F-75013, France. toby.hocking@inria.fr
authors.forename: Toby Dylan
authors.initials: TD
authors.lastname: Hocking
authors.forename: Gudrun
authors.initials: G
authors.lastname: Schleiermacher
authors.forename: Isabelle
authors.initials: I
authors.lastname: Janoueix-Lerosey
authors.forename: Valentina
authors.initials: V
authors.lastname: Boeva
authors.forename: Julie
authors.initials: J
authors.lastname: Cappo
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.forename: Francis
authors.initials: F
authors.lastname: Bach
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Vert
mesh_terms: D000465:Algorithms; D056905:Chromosome Breakpoints; D002874:Chromosome Mapping / Q000379:methods; D018628:Gene Dosage / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008957:Models, Genetic