Analysis of dose-response effects on gene expression data with comparison of two microarray platforms.
BACKGROUND
The problems of analyzing dose effects on gene expression are gaining attention in biomedical research. A specific challenge is to detect genes with expression levels that change according to dose levels in a non-random manner, but nonetheless may be considered as potential biomarkers.


METHODS
We are among the first to formally apply a tool that uses an isotonic (monotonic) regression approach to this area of study. We introduce a test statistic to select genes with significant dose-response expression in a monotonic fashion based on a permutation procedure. We then compare the results with those achieved from the application of a likelihood ratio-based test.


RESULTS
We apply the isotonic regression approach to a study of gene expression in the RKO colon carcinoma cell line in response to varying dosage levels of the chemotherapeutic agent 5-fluorouracil. A feature of both Affymetrix and printed 75mer oligomer cDNA arrays produced from the same samples provides an opportunity to compare the two microarray platforms.


BACKGROUND
Statistical software S-plus Code to implement the method is available from the authors.


BACKGROUND
kcoombes@mdanderson.org
Hu
Jianhua
J
Department of Biostatistics and Applied Mathematics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Kapoor
Mini
M
Zhang
Wei
W
Hamilton
Stanley R
SR
Coombes
Kevin R
KR
D000465:Algorithms; D000970:Antineoplastic Agents / Q000008:administration & dosage; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000008:administration & dosage*; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D005472:Fluorouracil