Bioinformatics Vol. 19 no. 3 2003
Pages 368-375
© 2003 Oxford University Press
Identifying differentially expressed genes using false discovery rate controlling procedures
Department of Statistics and Operations Research, The Sackler Faculty of Exact Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel
Received on August 14, 2001
; revised on June 20, 2002 and September 5, 2002
; accepted on September 9, 2002
Motivation: DNA microarrays have recently been used for the purpose of monitoring expression levels of thousands of genes simultaneously and identifying those genes that are differentially expressed. The probability that a false identification (type I error) is committed can increase sharply when the number of tested genes gets large. Correlation between the test statistics attributed to gene co-regulation and dependency in the measurement errors of the gene expression levels further complicates the problem. In this paper we address this very large multiplicity problem by adopting the false discovery rate (FDR) controlling approach. In order to address the dependency problem, we present three resampling-based FDR controlling procedures, that account for the test statistics distribution, and compare their performance to that of the naïve application of the linear step-up procedure in Benjamini and Hochberg (1995). The procedures are studied using simulated microarray data, and their performance is examined relative to their ease of implementation.
Results: Comparative simulation analysis shows that all four FDR controlling procedures control the FDR at the desired level, and retain substantially more power then the family-wise error rate controlling procedures. In terms of power, using resampling of the marginal distribution of each test statistics substantially improves the performance over the naïve one. The highest power is achieved, at the expense of a more sophisticated algorithm, by the resampling-based procedures that resample the joint distribution of the test statistics and estimate the level of FDR control.
Availability: An R program that adjusts p-values using FDR controlling procedures is freely available over the Internet at www.math.tau.ac.il/~ybenja
Contact: anatr{at}post.tau.ac.il
* To whom correspondence should be addressed.
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
M. E. Andersen, H. J. Clewell III, E. Bermudez, G. A. Willson, and R. S. Thomas Genomic Signatures and Dose-Dependent Transitions in Nasal Epithelial Responses to Inhaled Formaldehyde in the Rat Toxicol. Sci., October 1, 2008; 105(2): 368 - 383. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Decramer, A. G. de Peredo, B. Breuil, H. Mischak, B. Monsarrat, J.-L. Bascands, and J. P. Schanstra Urine in Clinical Proteomics Mol. Cell. Proteomics, October 1, 2008; 7(10): 1850 - 1862. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Okabe, G. Szakacs, M. A. Reimers, T. Suzuki, M. D. Hall, T. Abe, J. N. Weinstein, and M. M. Gottesman Profiling SLCO and SLC22 genes in the NCI-60 cancer cell lines to identify drug uptake transporters Mol. Cancer Ther., September 1, 2008; 7(9): 3081 - 3091. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Farcomeni A review of modern multiple hypothesis testing, with particular attention to the false discovery proportion Statistical Methods in Medical Research, August 1, 2008; 17(4): 347 - 388. [Abstract] [PDF] |
||||
![]() |
F. Yi, L. Pereira, and B. J. Merrill Tcf3 Functions as a Steady-State Limiter of Transcriptional Programs of Mouse Embryonic Stem Cell Self-Renewal Stem Cells, August 1, 2008; 26(8): 1951 - 1960. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. M. Smith, M. A. Cake, P. Ghosh, A. Schiavinato, R. A. Read, and C. B. Little Significant synovial pathology in a meniscectomy model of osteoarthritis: modification by intra-articular hyaluronan therapy Rheumatology, August 1, 2008; 47(8): 1172 - 1178. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Wang, J. You, K. G. Bemis, T. J. Tegeler, and D. P. G. Brown Label-free mass spectrometry-based protein quantification technologies in proteomic analysis Brief Funct Genomic Proteomic, June 25, 2008; (2008) eln031v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. S. Roberts, R. S. Thomas, and D. C. Dorman Gene Expression Changes Following Acute Hydrogen Sulfide (H2S)-induced Nasal Respiratory Epithelial Injury Toxicol Pathol, June 1, 2008; 36(4): 560 - 567. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Dragin, Z. Shi, R. Madan, C. L. Karp, M. A. Sartor, C. Chen, F. J. Gonzalez, and D. W. Nebert Phenotype of the Cyp1a1/1a2/1b1(-/-) Triple-Knockout Mouse Mol. Pharmacol., June 1, 2008; 73(6): 1844 - 1856. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. C. Lopez-Martin, M. Becana, L. C. Romero, and C. Gotor Knocking Out Cytosolic Cysteine Synthesis Compromises the Antioxidant Capacity of the Cytosol to Maintain Discrete Concentrations of Hydrogen Peroxide in Arabidopsis Plant Physiology, June 1, 2008; 147(2): 562 - 572. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Inada, A. Follenzi, K. Cheng, M. Surana, B. Joseph, D. Benten, S. Bandi, H. Qian, and S. Gupta Phenotype reversion in fetal human liver epithelial cells identifies the role of an intermediate meso-endodermal stage before hepatic maturation J. Cell Sci., April 1, 2008; 121(7): 1002 - 1013. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. G. Lavery, E. A. Walker, N. Turan, D. Rogoff, J. W. Ryder, J. M. Shelton, J. A. Richardson, F. Falciani, P. C. White, P. M. Stewart, et al. Deletion of Hexose-6-phosphate Dehydrogenase Activates the Unfolded Protein Response Pathway and Induces Skeletal Myopathy J. Biol. Chem., March 28, 2008; 283(13): 8453 - 8461. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. J. Campbell, H. S. Deshmukh, C. L. Nelson, I.-G. Bae, M. E. Stryjewski, J. J. Federspiel, G. T. Tonthat, T. H. Rude, S. L. Barriere, R. Corey, et al. Genotypic Characteristics of Staphylococcus aureus Isolates from a Multinational Trial of Complicated Skin and Skin Structure Infections J. Clin. Microbiol., February 1, 2008; 46(2): 678 - 684. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. N. Anderson, F. Roncaroli, A. Hodges, M. Deprez, and F. E. Turkheimer Chromosomal profiles of gene expression in Huntington's disease Brain, February 1, 2008; 131(2): 381 - 388. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Cordero, M. Botta, and R. A. Calogero Microarray data analysis and mining approaches Brief Funct Genomic Proteomic, January 22, 2008; (2008) elm034v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Nettleton, J. Recknor, and J. M. Reecy Identification of differentially expressed gene categories in microarray studies using nonparametric multivariate analysis Bioinformatics, January 15, 2008; 24(2): 192 - 201. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Hindre, H. Bruggemann, C. Buchrieser, and Y. Hechard Transcriptional profiling of Legionella pneumophila biofilm cells and the influence of iron on biofilm formation Microbiology, January 1, 2008; 154(1): 30 - 41. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. J. Loor, R. E. Everts, M. Bionaz, H. M. Dann, D. E. Morin, R. Oliveira, S. L. Rodriguez-Zas, J. K. Drackley, and H. A. Lewin Nutrition-induced ketosis alters metabolic and signaling gene networks in liver of periparturient dairy cows Physiol Genomics, December 19, 2007; 32(1): 105 - 116. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. E. Counts, B. He, S. Che, M. D. Ikonomovic, S. T. DeKosky, S. D. Ginsberg, and E. J. Mufson {alpha}7 Nicotinic Receptor Up-regulation in Cholinergic Basal Forebrain Neurons in Alzheimer Disease Arch Neurol, December 1, 2007; 64(12): 1771 - 1776. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. M. Levin, R. P. de Vries, A. Conesa, C. de Bekker, M. Talon, H. H. Menke, N. N. M. E. van Peij, and H. A. B. Wosten Spatial Differentiation in the Vegetative Mycelium of Aspergillus niger Eukaryot. Cell, December 1, 2007; 6(12): 2311 - 2322. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Rottscheidt and B. Harr Extensive Additivity of Gene Expression Differentiates Subspecies of the House Mouse Genetics, November 1, 2007; 177(3): 1553 - 1567. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Bodyak, J. C. Ayus, S. Achinger, V. Shivalingappa, Q. Ke, Y.-S. Chen, D. L. Rigor, I. Stillman, H. Tamez, P. E. Kroeger, et al. Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals PNAS, October 23, 2007; 104(43): 16810 - 16815. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. D. Moffat, P. C. Boutros, T. Celius, J. Linden, R. Pohjanvirta, and A. B. Okey microRNAs in Adult Rodent Liver Are Refractory to Dioxin Treatment Toxicol. Sci., October 1, 2007; 99(2): 470 - 487. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Fan and Y. Niu Selection and validation of normalization methods for c-DNA microarrays using within-array replications Bioinformatics, September 15, 2007; 23(18): 2391 - 2398. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. V. de Sa, M. L. Correa-Giannella, M. C. Machado, K. Krogh, M. Q. de Almeida, M. A. Albergaria Pereira, S. A. Coelho Siqueira, R. A. Patzina, F. S. Ibuki, M. C. Sogayar, et al. Serpin Peptidase Inhibitor Clade A Member 1 as a Potential Marker for Malignancy in Insulinomas Clin. Cancer Res., September 15, 2007; 13(18): 5322 - 5330. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. C. Kaizer, C. L. Glaser, D. Chaussabel, J. Banchereau, V. Pascual, and P. C. White Gene Expression in Peripheral Blood Mononuclear Cells from Children with Diabetes J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3705 - 3711. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Reiner-Benaim, D. Yekutieli, N. E. Letwin, G. I. Elmer, N. H. Lee, N. Kafkafi, and Y. Benjamini Associating quantitative behavioral traits with gene expression in the brain: searching for diamonds in the hay Bioinformatics, September 1, 2007; 23(17): 2239 - 2246. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Fadloun, D. Kobi, J.-C. Pointud, A. K. Indra, M. Teletin, C. Bole-Feysot, B. Testoni, R. Mantovani, D. Metzger, G. Mengus, et al. The TFIID subunit TAF4 regulates keratinocyte proliferation and has cell-autonomous and non-cell-autonomous tumour suppressor activity in mouse epidermis Development, August 15, 2007; 134(16): 2947 - 2958. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Juszczynski, J. Ouyang, S. Monti, S. J. Rodig, K. Takeyama, J. Abramson, W. Chen, J. L. Kutok, G. A. Rabinovich, and M. A. Shipp The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma PNAS, August 7, 2007; 104(32): 13134 - 13139. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. P Read, R A. Word, M. A Ruscheinsky, B. C Timmons, and M. S Mahendroo Cervical remodeling during pregnancy and parturition: molecular characterization of the softening phase in mice Reproduction, August 1, 2007; 134(2): 327 - 340. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Sykacek, R. Clarkson, C. Print, R. Furlong, and G. Micklem Bayesian modelling of shared gene function Bioinformatics, August 1, 2007; 23(15): 1936 - 1944. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Diaz-Uriarte, A. Alibes, E. R. Morrissey, A. Canada, O. M. Rueda, and M. L. Neves Asterias: integrated analysis of expression and aCGH data using an open-source, web-based, parallelized software suite Nucleic Acids Res., July 13, 2007; 35(suppl_2): W75 - W80. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. L. Volger, J. O. Fledderus, N. Kisters, R. D. Fontijn, P. D. Moerland, J. Kuiper, T. J. van Berkel, A.-P. J.J. Bijnens, M. J.A.P. Daemen, H. Pannekoek, et al. Distinctive Expression of Chemokines and Transforming Growth Factor-{beta} Signaling in Human Arterial Endothelium during Atherosclerosis Am. J. Pathol., July 1, 2007; 171(1): 326 - 337. [Abstract] [Full Text] [PDF] |
||||
![]() |
C.-F. Chen and C.-H. Cheng Regulation of Cellular Metabolism and Cytokines by the Medicinal Herb Feverfew in the Human Monocytic THP-1 Cells Evid. Based Complement. Altern. Med., June 11, 2007; (2007) nem061v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Sanchez-Carbayo, N. D. Socci, T. Kirchoff, N. Erill, K. Offit, B. H. Bochner, and C. Cordon-Cardo A Polymorphism in HDM2 (SNP309) Associates with Early Onset in Superficial Tumors, TP53 Mutations, and Poor Outcome in Invasive Bladder Cancer Clin. Cancer Res., June 1, 2007; 13(11): 3215 - 3220. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Shemesh, A. Tam, and D. Steinberg Differential gene expression profiling of Streptococcus mutans cultured under biofilm and planktonic conditions Microbiology, May 1, 2007; 153(5): 1307 - 1317. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. S. Thomas, L. Pluta, L. Yang, and T. A. Halsey Application of Genomic Biomarkers to Predict Increased Lung Tumor Incidence in 2-Year Rodent Cancer Bioassays Toxicol. Sci., May 1, 2007; 97(1): 55 - 64. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Lasanthi-Kudahettige, L. Magneschi, E. Loreti, S. Gonzali, F. Licausi, G. Novi, O. Beretta, F. Vitulli, A. Alpi, and P. Perata Transcript Profiling of the Anoxic Rice Coleoptile Plant Physiology, May 1, 2007; 144(1): 218 - 231. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Heguy, B.-G. Harvey, P. L. Leopold, I. Dolgalev, T. Raman, and R. G. Crystal Responses of the human airway epithelium transcriptome to in vivo injury Physiol Genomics, April 24, 2007; 29(2): 139 - 148. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. Cholet, A. Henaut, S. Casaregola, and P. Bonnarme Gene Expression and Biochemical Analysis of Cheese-Ripening Yeasts: Focus on Catabolism of L-Methionine, Lactate, and Lactose Appl. Envir. Microbiol., April 15, 2007; 73(8): 2561 - 2570. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Golland, S. Bentin, H. Gelbard, Y. Benjamini, R. Heller, Y. Nir, U. Hasson, and R. Malach Extrinsic and Intrinsic Systems in the Posterior Cortex of the Human Brain Revealed during Natural Sensory Stimulation Cereb Cortex, April 1, 2007; 17(4): 766 - 777. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Marchet, S. Mocellin, C. Belluco, A. Ambrosi, F. DeMarchi, E. Mammano, M. Digito, A. Leon, A. D'Arrigo, M. Lise, et al. Gene Expression Profile of Primary Gastric Cancer: Towards the Prediction of Lymph Node Status Ann. Surg. Oncol., March 1, 2007; 14(3): 1058 - 1064. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. S. Thomas, T. M. O'Connell, L. Pluta, R. D. Wolfinger, L. Yang, and T. J. Page A Comparison of Transcriptomic and Metabonomic Technologies for Identifying Biomarkers Predictive of Two-Year Rodent Cancer Bioassays Toxicol. Sci., March 1, 2007; 96(1): 40 - 46. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Lamant, A. d. Reynies, M.-M. Duplantier, D. S. Rickman, F. Sabourdy, S. Giuriato, L. Brugieres, P. Gaulard, E. Espinos, and G. Delsol Gene-expression profiling of systemic anaplastic large-cell lymphoma reveals differences based on ALK status and two distinct morphologic ALK+ subtypes Blood, March 1, 2007; 109(5): 2156 - 2164. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M. Polo, P. Juszczynski, S. Monti, L. Cerchietti, K. Ye, J. M. Greally, M. Shipp, and A. Melnick Transcriptional signature with differential expression of BCL6 target genes accurately identifies BCL6-dependent diffuse large B cell lymphomas PNAS, February 27, 2007; 104(9): 3207 - 3212. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Lerman, J. McQuown, A. Blais, B. D. Dynlacht, G. Chen, and B. Mishra Functional genomics via multiscale analysis: application to gene expression and ChIP-on-chip data Bioinformatics, February 1, 2007; 23(3): 314 - 320. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. T. Johnson, R. A. Harris, P. V. Blair, and R. S. Balaban Functional consequences of mitochondrial proteome heterogeneity Am J Physiol Cell Physiol, February 1, 2007; 292(2): C698 - C707. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. J. Loor, H. M. Dann, N. A. J. Guretzky, R. E. Everts, R. Oliveira, C. A. Green, N. B. Litherland, S. L. Rodriguez-Zas, H. A. Lewin, and J. K. Drackley Plane of nutrition prepartum alters hepatic gene expression and function in dairy cows as assessed by longitudinal transcript and metabolic profiling Physiol Genomics, January 12, 2007; 27(1): 29 - 41. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Voolstra, D. Tautz, P. Farbrother, L. Eichinger, and B. Harr Contrasting evolution of expression differences in the testis between species and subspecies of the house mouse Genome Res., January 1, 2007; 17(1): 42 - 49. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. R. Swindell The Association Among Gene Expression Responses to Nine Abiotic Stress Treatments in Arabidopsis thaliana Genetics, December 1, 2006; 174(4): 1811 - 1824. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. L. Getchell, H. Li, R. A. Vaishnav, A. S. Borders, J. Witta, N. Subhedar, W. de Villiers, A. J. Stromberg, and T. V. Getchell Temporal gene expression profiles of target-ablated olfactory epithelium in mice with disrupted expression of scavenger receptor A: impact on macrophages Physiol Genomics, November 21, 2006; 27(3): 245 - 263. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. O. Martinez, S. Gordon, M. Locati, and A. Mantovani Transcriptional Profiling of the Human Monocyte-to-Macrophage Differentiation and Polarization: New Molecules and Patterns of Gene Expression J. Immunol., November 15, 2006; 177(10): 7303 - 7311. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. K. Glebov, L. M. Rodriguez, P. Soballe, J. DeNobile, J. Cliatt, K. Nakahara, and I. R. Kirsch Gene Expression Patterns Distinguish Colonoscopically Isolated Human Aberrant Crypt Foci from Normal Colonic Mucosa. Cancer Epidemiol. Biomarkers Prev., November 1, 2006; 15(11): 2253 - 2262. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. A. Hannah, D. Wiese, S. Freund, O. Fiehn, A. G. Heyer, and D. K. Hincha Natural Genetic Variation of Freezing Tolerance in Arabidopsis Plant Physiology, September 1, 2006; 142(1): 98 - 112. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Pounds and C. Cheng Robust estimation of the false discovery rate Bioinformatics, August 15, 2006; 22(16): 1979 - 1987. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Fan and Y. Ren Statistical Analysis of DNA Microarray Data in Cancer Research Clin. Cancer Res., August 1, 2006; 12(15): 4469 - 4473. [Abstract] [Full Text] [PDF] |
||||
![]() |




































