caa a22 4500 378926128 CHVBK 20180305123617.0 cr unu---uuuuu 161128e20041219xx s 000 0 eng 10.2202/1544-6115.1064 doi (NATIONALLICENCE)gruyter-10.2202/1544-6115.1064 Statistical Significance Threshold Criteria For Analysis of Microarray Gene Expression Data [Elektronische Daten] [Cheng Cheng, Stanley B. Pounds, James M. Boyett, Deqing Pei, Mei-Ling Kuo, Martine F. Roussel] The methodological advancement in microarray data analysis on the basis of false discovery rate (FDR) control, such as the q-value plots, allows the investigator to examine the FDR from several perspectives. However, when FDR control at the "customary" levels 0.01, 0.05, or 0.1 does not provide fruitful findings, there is little guidance for making the trade off between the significance threshold and the FDR level by sound statistical or biological considerations. Thus, meaningful statistical significance criteria that complement the existing FDR methods for large-scale multiple tests are desirable. Three statistical significance criteria, the profile information criterion, the total error proportion, and the guide-gene driven selection, are developed in this research. The first two are general significance threshold criteria for large-scale multiple tests; the profile information criterion is related to the recent theoretical studies of the connection between FDR control and minimax estimation, and the total error proportion is closely related to the asymptotic properties of FDR control in terms of the total error risk. The guide-gene driven selection is an approach to combining statistical significance and the existing biological knowledge of the study at hand. Error properties of these criteria are investigated theoretically and by simulation. The proposed methods are illustrated and compared using an example of genomic screening for novel Arf gene targets. Operating characteristics of q-value and the proposed significance threshold criteria are investigated and compared in a simulation study that employs a model mimicking a gene regulatory pathway. A guideline for using these criteria is provided. Splus/R code is available from the corresponding author upon request. ©2011 Walter de Gruyter GmbH & Co. KG, Berlin/Boston Statistical Theory and Methods nationallicence Microarrays nationallicence multiple tests nationallicence significance threshold selection nationallicence profile information criterion nationallicence total error proportion nationallicence false discovery rate nationallicence q-value nationallicence microarray nationallicence gene expression nationallicence Cheng Cheng Department of Biostatistics, St. Jude Children's Research Hospital aut Pounds Stanley B. Department of Biostatistics, St. Jude Children's Research Hospital aut Boyett James M. Department of Biostatistics, St. Jude Children's Research Hospital aut Pei Deqing Department of Biostatistics, St. Jude Children's Research Hospital aut Kuo Mei-Ling Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital aut Roussel Martine F. Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital aut Statistical Applications in Genetics and Molecular Biology De Gruyter 3/1(2004-12-19), 1-30 3:1<1 2004 3 sagmb https://doi.org/10.2202/1544-6115.1064 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.2202/1544-6115.1064 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Cheng Cheng Department of Biostatistics, St. Jude Children's Research Hospital aut NATIONALLICENCE 700 1- Pounds Stanley B. Department of Biostatistics, St. Jude Children's Research Hospital aut NATIONALLICENCE 700 1- Boyett James M. Department of Biostatistics, St. Jude Children's Research Hospital aut NATIONALLICENCE 700 1- Pei Deqing Department of Biostatistics, St. Jude Children's Research Hospital aut NATIONALLICENCE 700 1- Kuo Mei-Ling Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital aut NATIONALLICENCE 700 1- Roussel Martine F. Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital aut NATIONALLICENCE 773 0- Statistical Applications in Genetics and Molecular Biology De Gruyter 3/1(2004-12-19), 1-30 3:1<1 2004 3 sagmb CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter