A New Test Statistic Based on Shrunken Sample Variance for Identifying Differentially Expressed Genes in Small Microarray Experiments

Choosing an appropriate statistic and precisely evaluating the false discovery rate (FDR) are both essential for devising an effective method for identifying differentially expressed genes in microarray data. The t-type score proposed by Pan et al. (2003) succeeded in suppressing false positives by...

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Main Authors: Isao Yoshimura, Chikuma Hamada, Yasunori Sato, Akihiro Hirakawa
Format: Article
Language:English
Published: SAGE Publishing 2008-01-01
Series:Bioinformatics and Biology Insights
Subjects:
Online Access:http://la-press.com/article.php?article_id=575
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author Isao Yoshimura
Chikuma Hamada
Yasunori Sato
Akihiro Hirakawa
author_facet Isao Yoshimura
Chikuma Hamada
Yasunori Sato
Akihiro Hirakawa
author_sort Isao Yoshimura
collection DOAJ
description Choosing an appropriate statistic and precisely evaluating the false discovery rate (FDR) are both essential for devising an effective method for identifying differentially expressed genes in microarray data. The t-type score proposed by Pan et al. (2003) succeeded in suppressing false positives by controlling the underestimation of variance but left the overestimation uncontrolled. For controlling the overestimation, we devised a new test statistic (variance stabilized t-type score) by placing shrunken sample variances of the James-Stein type in the denominator of the t-type score. Since the relative superiority of the mean and median FDRs was unclear in the widely adopted Significance Analysis of Microarrays (SAM), we conducted simulation studies to examine the performance of the variance stabilized t-type score and the characteristics of the two FDRs. The variance stabilized t-type score was generally better than or at least as good as the t-type score, irrespective of the sample size and proportion of differentially expressed genes. In terms of accuracy, the median FDR was superior to the mean FDR when the proportion of differentially expressed genes was large. The variance stabilized t-type score with the median FDR was applied to actual colorectal cancer data and yielded a reasonable result.
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spelling doaj.art-da2308d4af3143e0ac00793bc39b2e302022-12-21T19:19:15ZengSAGE PublishingBioinformatics and Biology Insights1177-93222008-01-012145156A New Test Statistic Based on Shrunken Sample Variance for Identifying Differentially Expressed Genes in Small Microarray ExperimentsIsao YoshimuraChikuma HamadaYasunori SatoAkihiro HirakawaChoosing an appropriate statistic and precisely evaluating the false discovery rate (FDR) are both essential for devising an effective method for identifying differentially expressed genes in microarray data. The t-type score proposed by Pan et al. (2003) succeeded in suppressing false positives by controlling the underestimation of variance but left the overestimation uncontrolled. For controlling the overestimation, we devised a new test statistic (variance stabilized t-type score) by placing shrunken sample variances of the James-Stein type in the denominator of the t-type score. Since the relative superiority of the mean and median FDRs was unclear in the widely adopted Significance Analysis of Microarrays (SAM), we conducted simulation studies to examine the performance of the variance stabilized t-type score and the characteristics of the two FDRs. The variance stabilized t-type score was generally better than or at least as good as the t-type score, irrespective of the sample size and proportion of differentially expressed genes. In terms of accuracy, the median FDR was superior to the mean FDR when the proportion of differentially expressed genes was large. The variance stabilized t-type score with the median FDR was applied to actual colorectal cancer data and yielded a reasonable result.http://la-press.com/article.php?article_id=575differentially expressed genesfalse discovery ratemicroarrayshrunken sample variancesignificance analysis of microarrayt-type score
spellingShingle Isao Yoshimura
Chikuma Hamada
Yasunori Sato
Akihiro Hirakawa
A New Test Statistic Based on Shrunken Sample Variance for Identifying Differentially Expressed Genes in Small Microarray Experiments
Bioinformatics and Biology Insights
differentially expressed genes
false discovery rate
microarray
shrunken sample variance
significance analysis of microarray
t-type score
title A New Test Statistic Based on Shrunken Sample Variance for Identifying Differentially Expressed Genes in Small Microarray Experiments
title_full A New Test Statistic Based on Shrunken Sample Variance for Identifying Differentially Expressed Genes in Small Microarray Experiments
title_fullStr A New Test Statistic Based on Shrunken Sample Variance for Identifying Differentially Expressed Genes in Small Microarray Experiments
title_full_unstemmed A New Test Statistic Based on Shrunken Sample Variance for Identifying Differentially Expressed Genes in Small Microarray Experiments
title_short A New Test Statistic Based on Shrunken Sample Variance for Identifying Differentially Expressed Genes in Small Microarray Experiments
title_sort new test statistic based on shrunken sample variance for identifying differentially expressed genes in small microarray experiments
topic differentially expressed genes
false discovery rate
microarray
shrunken sample variance
significance analysis of microarray
t-type score
url http://la-press.com/article.php?article_id=575
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