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.
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.
Sutter
Thomas R
TR
W. Harry Feinstone Center for Genomic Research, University of Memphis, Memphis, Tennessee 38152, USA. tsutter@memphis.edu
He
Xiao-Rui
XR
Dimitrov
Peter
P
Xu
Lijing
L
Narasimhan
Giri
G
George
E Olusegun
EO
Sutter
Carrie Hayes
CH
Grubbs
Clinton
C
Savory
Richard
R
Stephan-Gueldner
Markus
M
Kreder
Dirk
D
Taylor
Michael J
MJ
Lubet
Ronald
R
Patterson
Tricia A
TA
Kensler
Thomas W
TW
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
D016588:Anticarcinogenic Agents; D012313:RNA