title: Multiple comparisons model-based clustering and ternary pattern tree numerical display of gene response to treatment: procedure and application to the preclinical evaluation of chemopreventive agents.
abstract: Microarray technology has greatly aided the identification of genes that are expressed differentially. Statistical analysis of such data by multiple comparisons procedures has been slow to develop, in part, because methods to cluster the results of such comparisons in biologically meaningful ways have not been available. We isolated and analyzed, by Northern blot and GeneChip, replicate liver RNA samples (n = 4/group) from rats fed with control diet or diet containing one of three chemopreventive compounds, selected because their pharmacological activities, including RNA expression response, are relatively well understood. We report on a classification tree, based on the results of nonparametric multiple comparisons, which results in the bipolar hierarchical clustering of genes in relation to their response to treatment. In addition to identifying treatment-responsive genes, application of this procedure to our test study identified the known pharmacological relationships among the treatment groups without supervision. Also, small treatment-specific subsets of genes were identified that may be indicative of additional pharmacophores present in the test compounds.
authors.affiliation: W. Harry Feinstone Center for Genomic Research, University of Memphis, Memphis, Tennessee 38152, USA. tsutter@memphis.edu
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Sutter
authors.forename: Xiao-Rui
authors.initials: XR
authors.lastname: He
authors.forename: Peter
authors.initials: P
authors.lastname: Dimitrov
authors.forename: Lijing
authors.initials: L
authors.lastname: Xu
authors.forename: Giri
authors.initials: G
authors.lastname: Narasimhan
authors.forename: E Olusegun
authors.initials: EO
authors.lastname: George
authors.forename: Carrie Hayes
authors.initials: CH
authors.lastname: Sutter
authors.forename: Clinton
authors.initials: C
authors.lastname: Grubbs
authors.forename: Richard
authors.initials: R
authors.lastname: Savory
authors.forename: Markus
authors.initials: M
authors.lastname: Stephan-Gueldner
authors.forename: Dirk
authors.initials: D
authors.lastname: Kreder
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Taylor
authors.forename: Ronald
authors.initials: R
authors.lastname: Lubet
authors.forename: Tricia A
authors.initials: TA
authors.lastname: Patterson
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Kensler
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008956:Models, Chemical; D015233:Models, Statistical; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012313:RNA / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012984:Software; D013223:Statistics as Topic / Q000379:methods; D015854:Up-Regulation
chemical_list: D016588:Anticarcinogenic Agents; D012313:RNA