A modified maximum contrast method for unequal sample sizes in pharmacogenomic studies

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Publication:139986

DOI10.2202/1544-6115.1560zbMATH Open1296.92057arXiv2012.03475OpenAlexW3112480960WikidataQ45922307 ScholiaQ45922307MaRDI QIDQ139986FDOQ139986

Kengo Nagashima, Yasunori Sato, Chikuma Hamada

Publication date: 7 January 2011

Published in: Statistical Applications in Genetics and Molecular Biology (Search for Journal in Brave)

Abstract: In pharmacogenomic studies, biomedical researchers commonly analyze the association between genotype and biological response by using the Kruskal--Wallis test or one-way analysis of variance (ANOVA) after logarithmic transformation of the obtained data. However, because these methods detect unexpected biological response patterns, the power for detecting the expected pattern is reduced. Previously, we proposed a combination of the maximum contrast method and the permuted modified maximum contrast method for unequal sample sizes in pharmacogenomic studies. However, we noted that the distribution of the permuted modified maximum contrast statistic depends on a nuisance parameter sigma2, which is the population variance. In this paper, we propose a modified maximum contrast method with a statistic that does not depend on the nuisance parameter. Furthermore, we compare the performance of these methods via simulation studies. The simulation results showed that the modified maximum contrast method gave the lowest false-positive rate; therefore, this method is powerful for detecting the true response patterns in some conditions. Further, it is faster and more accurate than the permuted modified maximum contrast method. On the basis of these results, we suggest a rule of thumb to select the appropriate method in a given situation.


Full work available at URL: https://arxiv.org/abs/2012.03475






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