title: A novel tree-based procedure for deciphering the genomic spectrum of clinical disease entities.
abstract: BACKGROUND
  Dissecting the genomic spectrum of clinical disease entities is a challenging task. Recursive partitioning (or classification trees) methods provide powerful tools for exploring complex interplay among genomic factors, with respect to a main factor, that can reveal hidden genomic patterns. To take confounding variables into account, the partially linear tree-based regression (PLTR) model has been recently published. It combines regression models and tree-based methodology. It is however computationally burdensome and not well suited for situations for which a large number of exploratory variables is expected.
  
  
  METHODS
  We developed a novel procedure that represents an alternative to the original PLTR procedure, and considered different selection criteria. A simulation study with different scenarios has been performed to compare the performances of the proposed procedure to the original PLTR strategy.
  
  
  RESULTS
  The proposed procedure with a Bayesian Information Criterion (BIC) achieved good performances to detect the hidden structure as compared to the original procedure. The novel procedure was used for analyzing patterns of copy-number alterations in lung adenocarcinomas, with respect to Kirsten Rat Sarcoma Viral Oncogene Homolog gene (KRAS) mutation status, while controlling for a cohort effect. Results highlight two subgroups of pure or nearly pure wild-type KRAS tumors with particular copy-number alteration patterns.
  
  
  CONCLUSIONS
  The proposed procedure with a BIC criterion represents a powerful and practical alternative to the original procedure. Our procedure performs well in a general framework and is simple to implement.
authors.affiliation: Abirisk consortium WP4, 14-16 Avenue Paul-Vaillant-Couturier, 94807 Villejuif, France ; Inserm U669, 14-16 Avenue Paul-Vaillant-Couturier, 94807 Villejuif, France.
authors.forename: Cyprien
authors.initials: C
authors.lastname: Mbogning
authors.affiliation: Inserm U669, 14-16 Avenue Paul-Vaillant-Couturier, 94807 Villejuif, France ; Faculty of Medicine Paris-Sud, 63 rue Gabriel Peri, 94276 Le Kremlin-Bicêtre, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Perdry
authors.affiliation: Inserm U669, 14-16 Avenue Paul-Vaillant-Couturier, 94807 Villejuif, France ; Faculty of Medicine Paris-Sud, 63 rue Gabriel Peri, 94276 Le Kremlin-Bicêtre, France.
authors.forename: Wilson
authors.initials: W
authors.lastname: Toussile
authors.affiliation: Abirisk consortium WP4, 14-16 Avenue Paul-Vaillant-Couturier, 94807 Villejuif, France ; Inserm U669, 14-16 Avenue Paul-Vaillant-Couturier, 94807 Villejuif, France ; Faculty of Medicine Paris-Sud, 63 rue Gabriel Peri, 94276 Le Kremlin-Bicêtre, France ; Assistance Publique - Hôpitaux de Paris, Hôpital Paul Brousse, Villejuif, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Broët
keywords: Disease taxonomy; Genomic; Lung cancer; Recursive partitioning; Tree-based regression
references.citation: J Clin Oncol. 2013 Mar 10;31(8):1112-21
references.pmid: 23401440
references.citation: Genet Epidemiol. 2007 Apr;31(3):238-51
references.pmid: 17266115
references.citation: J Clin Bioinforma. 2012 May 22;2(1):13
references.pmid: 22616791
references.citation: J Biomed Inform. 2011 Dec;44(6):936-42
references.pmid: 21703362
references.citation: BMC Bioinformatics. 2006 Jan 06;7:3
references.pmid: 16398926
references.citation: Biometrics. 2010 Mar;66(1):89-96
references.pmid: 19432770
references.citation: Clin Cancer Res. 2011 Jun 1;17(11):3542-50
references.pmid: 21521776
references.citation: Nature. 2004 Nov 18;432(7015):338-41
references.pmid: 15549096