MOTIVATION: 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. METHOD: 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. AVAILABILITY: Statistical software S-plus Code to implement the method is available from the authors. CONTACT: kcoombes@mdanderson.org
MOTIVATION: 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. METHOD: 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. AVAILABILITY: Statistical software S-plus Code to implement the method is available from the authors. CONTACT: kcoombes@mdanderson.org
Authors: Kévin Le Brigand; Roslin Russell; Chimène Moreilhon; Jean-Marie Rouillard; Bernard Jost; Franck Amiot; Virginie Magnone; Christine Bole-Feysot; Philippe Rostagno; Virginie Virolle; Virginie Defamie; Philippe Dessen; Gary Williams; Paul Lyons; Géraldine Rios; Bernard Mari; Erdogan Gulari; Philippe Kastner; Xavier Gidrol; Tom C Freeman; Pascal Barbry Journal: Nucleic Acids Res Date: 2006-07-19 Impact factor: 16.971
Authors: Joshua A Harrill; Zhen Li; Fred A Wright; Nicholas M Radio; William R Mundy; Rogelio Tornero-Velez; Kevin M Crofton Journal: BMC Genomics Date: 2008-11-18 Impact factor: 3.969
Authors: William O Ward; Carol D Swartz; Steffen Porwollik; Sarah H Warren; Nancy M Hanley; Geremy W Knapp; Michael McClelland; David M DeMarini Journal: BMC Bioinformatics Date: 2007-10-09 Impact factor: 3.169