Bioinformatics Vol. 18 no. 90001 2002
Pages S96-S104
© 2002 Oxford University Press
Variance stabilization applied to microarray data calibration and to the quantification of differential expression
1 Department of Molecular Genome Analysis, German Cancer Research Center,
INF 280, Heidelberg, 69120, Germany
2 Department of Computational Molecular Biology, Max-Planck-Institute for Molecular Genetics,
Dahlem, Berlin, 14195, Germany
Received on January 24, 2002
; revised on March 30, 2002
; accepted on March 30, 2002
We introduce a statistical model for microarray gene expression data
that comprises data calibration, the quantification of differential
expression, and the quantification of measurement error.
In particular, we derive a transformation h for intensity measurements,
and a difference statistic 
h whose variance is approximately constant
along the whole intensity range.
This forms a basis for statistical inference from microarray data,
and provides a rational data pre-processing strategy for multivariate
analyses.
For the transformation h, the parametric form h(x)=arsinh(a+bx)
is derived from a model of the variance-versus-mean dependence for
microarray intensity data, using the method of variance stabilizing
transformations.
For large intensities, h coincides with the logarithmic transformation,
and h with the log-ratio.
The parameters of h together with those of the calibration between experiments
are estimated with a robust variant of maximum-likelihood estimation.
We demonstrate our approach on data sets from different experimental
platforms, including two-colour cDNA arrays and a series of
Affymetrix oligonucleotide arrays.
Availability: Software is freely available for academic use as an R package at http://www.dkfz.de/abt0840/whuber
Contact: w.huber{at}dkfz.de
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Dierlamm, E. M. Murga Penas, S. Bentink, S. Wessendorf, H. Berger, M. Hummel, W. Klapper, D. Lenze, A. Rosenwald, E. Haralambieva, et al. Gain of chromosome region 18q21 including the MALT1 gene is associated with the activated B-cell-like gene expression subtype and increased BCL2 gene dosage and protein expression in diffuse large B-cell lymphoma Haematologica, May 1, 2008; 93(5): 688 - 696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Van Vlierberghe, M. van Grotel, J. Tchinda, C. Lee, H. B. Beverloo, P. J. van der Spek, A. Stubbs, J. Cools, K. Nagata, M. Fornerod, et al. The recurrent SET-NUP214 fusion as a new HOXA activation mechanism in pediatric T-cell acute lymphoblastic leukemia Blood, May 1, 2008; 111(9): 4668 - 4680. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Petropoulos, N. Arseni, C. Schessl, C. R. Stadler, V. P.S. Rawat, A. J. Deshpande, B. Heilmeier, W. Hiddemann, L. Quintanilla-Martinez, S. K. Bohlander, et al. A novel role for Lef-1, a central transcription mediator of Wnt signaling, in leukemogenesis J. Exp. Med., March 17, 2008; 205(3): 515 - 522. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bak, A. Silahtaroglu, M. Moller, M. Christensen, M. F. Rath, B. Skryabin, N. Tommerup, and S. Kauppinen MicroRNA expression in the adult mouse central nervous system RNA, March 1, 2008; 14(3): 432 - 444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Lin, P. Du, W. Huber, and W. A. Kibbe Model-based variance-stabilizing transformation for Illumina microarray data Nucleic Acids Res., February 2, 2008; 36(2): e11 - e11. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Mitko, S. E Ulbrich, H. Wenigerkind, F. Sinowatz, H. Blum, E. Wolf, and S. Bauersachs Dynamic changes in messenger RNA profiles of bovine endometrium during the oestrous cycle Reproduction, February 1, 2008; 135(2): 225 - 240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kelley, H. Feizi, and T. Ideker Correcting for gene-specific dye bias in DNA microarrays using the method of maximum likelihood Bioinformatics, January 1, 2008; 24(1): 71 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. P. S. Rawat, S. Thoene, V. M. Naidu, N. Arseni, B. Heilmeier, K. Metzeler, K. Petropoulos, A. Deshpande, L. Quintanilla-Martinez, S. K. Bohlander, et al. Overexpression of CDX2 perturbs HOX gene expression in murine progenitors depending on its N-terminal domain and is closely correlated with deregulated HOX gene expression in human acute myeloid leukemia Blood, January 1, 2008; 111(1): 309 - 319. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. F. Sempere, M. Christensen, A. Silahtaroglu, M. Bak, C. V. Heath, G. Schwartz, W. Wells, S. Kauppinen, and C. N. Cole Altered MicroRNA Expression Confined to Specific Epithelial Cell Subpopulations in Breast Cancer Cancer Res., December 15, 2007; 67(24): 11612 - 11620. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Hornan, S. N. Peirson, A. J. Hardcastle, R. S. Molday, M. E. Cheetham, and A. R. Webster Novel Retinal and Cone Photoreceptor Transcripts Revealed by Human Macular Expression Profiling Invest. Ophthalmol. Vis. Sci., December 1, 2007; 48(12): 5388 - 5396. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Brazas, E. B. M. Breidenstein, J. Overhage, and R. E. W. Hancock Role of Lon, an ATP-Dependent Protease Homolog, in Resistance of Pseudomonas aeruginosa to Ciprofloxacin Antimicrob. Agents Chemother., December 1, 2007; 51(12): 4276 - 4283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Pan, X. Luo, T. Toloubeydokhti, and N. Chegini The expression profile of micro-RNA in endometrium and endometriosis and the influence of ovarian steroids on their expression Mol. Hum. Reprod., November 1, 2007; 13(11): 797 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Ritchie, J. Silver, A. Oshlack, M. Holmes, D. Diyagama, A. Holloway, and G. K. Smyth A comparison of background correction methods for two-colour microarrays Bioinformatics, October 15, 2007; 23(20): 2700 - 2707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Thomassen, Q. Tan, F. Eiriksdottir, M. Bak, S. Cold, and T. A. Kruse Comparison of Gene Sets for Expression Profiling: Prediction of Metastasis from Low-Malignant Breast Cancer Clin. Cancer Res., September 15, 2007; 13(18): 5355 - 5360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Dubouzet, A. Ishihara, F. Matsuda, H. Miyagawa, H. Iwata, and K. Wakasa Integrated metabolomic and transcriptomic analyses of high-tryptophan rice expressing a mutant anthranilate synthase alpha subunit J. Exp. Bot., September 4, 2007; (2007) erm179v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bauersachs, K. Mitko, H. Blum, and E. Wolf Technical Note: Bovine Oviduct and Endometrium Array Version 1: A Tailored Tool for Studying Bovine Endometrium Biology and Pathophysiology J Dairy Sci, September 1, 2007; 90(9): 4420 - 4423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Westermann, K.-O. Henrich, J. S. Wei, W. Lutz, M. Fischer, R. Konig, R. Wiedemeyer, V. Ehemann, B. Brors, K. Ernestus, et al. High Skp2 Expression Characterizes High-Risk Neuroblastomas Independent of MYCN Status Clin. Cancer Res., August 15, 2007; 13(16): 4695 - 4703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Thum, P. Galuppo, C. Wolf, J. Fiedler, S. Kneitz, L. W. van Laake, P. A. Doevendans, C. L. Mummery, J. Borlak, A. Haverich, et al. MicroRNAs in the Human Heart: A Clue to Fetal Gene Reprogramming in Heart Failure Circulation, July 17, 2007; 116(3): 258 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sundaresh, A. Randall, B. Unal, J. M. Petersen, J. T. Belisle, M. Gill Hartley, M. Duffield, R. W. Titball, D. H. Davies, P. L. Felgner, et al. From protein microarrays to diagnostic antigen discovery: a study of the pathogen Francisella tularensis Bioinformatics, July 1, 2007; 23(13): i508 - i518. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Schultze and D. Eggle IlluminaGUI: Graphical User Interface for analyzing gene expression data generated on the Illumina platform Bioinformatics, June 1, 2007; 23(11): 1431 - 1433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Chuchana, D. Marchand, M. Nugoli, C. Rodriguez, N. Molinari, and J. A. Garcia-Sanz An adaptation of the LMS method to determine expression variations in profiling data Nucleic Acids Res., May 14, 2007; 35(9): e71 - e71. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Quackenbush Extracting biology from high-dimensional biological data J. Exp. Biol., May 1, 2007; 210(9): 1507 - 1517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. E. Tissing, M. L. den Boer, J. P. P. Meijerink, R. X. Menezes, S. Swagemakers, P. J. van der Spek, S. E. Sallan, S. A. Armstrong, and R. Pieters Genomewide identification of prednisolone-responsive genes in acute lymphoblastic leukemia cells Blood, May 1, 2007; 109(9): 3929 - 3935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Davey, G. Savva, J. Dicks, and I. N. Roberts MPP: a microarray-to-phylogeny pipeline for analysis of gene and marker content datasets Bioinformatics, April 15, 2007; 23(8): 1023 - 1025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nacu, R. Critchley-Thorne, P. Lee, and S. Holmes Gene expression network analysis and applications to immunology Bioinformatics, April 1, 2007; 23(7): 850 - 858. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. McRae, N. A. Matigian, L. Vadlamudi, J. C. Mulley, B. Mowry, N. G. Martin, S. F. Berkovic, N. K. Hayward, and P. M. Visscher Replicated effects of sex and genotype on gene expression in human lymphoblastoid cell lines Hum. Mol. Genet., February 15, 2007; 16(4): 364 - 373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Reah, M. O'Gorman, A. Borthwick, D. Miller, and D. Bramwell P15-T SameSpots: Validating a Novel Approach to 2D Electrophoresis Image Analysis J. Biomol. Tech., February 1, 2007; 18(1): 6 - 6. [Abstract] [PDF]
|
|
|
|
|
|
M. Friedmann, S. G. Ralph, D. Aeschliman, J. Zhuang, K. Ritland, B. E. Ellis, J. Bohlmann, and C. J. Douglas Microarray gene expression profiling of developmental transitions in Sitka spruce (Picea sitchensis) apical shoots J. Exp. Bot., February 1, 2007; 58(3): 593 - 614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Jaeger, D. Koczan, H.-J. Thiesen, S. M. Ibrahim, G. Gross, R. Spang, and M. Kunz Gene Expression Signatures for Tumor Progression, Tumor Subtype, and Tumor Thickness in Laser-Microdissected Melanoma Tissues Clin. Cancer Res., February 1, 2007; 13(3): 806 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Lo and R. Gottardo Flexible empirical Bayes models for differential gene expression Bioinformatics, February 1, 2007; 23(3): 328 - 335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Yuan and R. A. Irizarry High-resolution spatial normalization for microarrays containing embedded technical replicates Bioinformatics, December 15, 2006; 22(24): 3054 - 3060. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Vogel, L. Guelen, E. de Wit, D. P. Hupkes, M. Loden, W. Talhout, M. Feenstra, B. Abbas, A.-K. Classen, and B. van Steensel Human heterochromatin proteins form large domains containing KRAB-ZNF genes Genome Res., December 1, 2006; 16(12): 1493 - 1504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yoon, Y. Yang, J. Choi, and J. Seong Large scale data mining approach for gene-specific standardization of microarray gene expression data Bioinformatics, December 1, 2006; 22(23): 2898 - 2904. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Deeken, J. C. Engelmann, M. Efetova, T. Czirjak, T. Muller, W. M. Kaiser, O. Tietz, M. Krischke, M. J. Mueller, K. Palme, et al. An Integrated View of Gene Expression and Solute Profiles of Arabidopsis Tumors: A Genome-Wide Approach PLANT CELL, December 1, 2006; 18(12): 3617 - 3634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Marsit, K. Eddy, and K. T. Kelsey MicroRNA Responses to Cellular Stress. Cancer Res., November 15, 2006; 66(22): 10843 - 10848. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Oberthuer, F. Berthold, P. Warnat, B. Hero, Y. Kahlert, R. Spitz, K. Ernestus, R. Konig, S. Haas, R. Eils, et al. Customized Oligonucleotide Microarray Gene Expression-Based Classification of Neuroblastoma Patients Outperforms Current Clinical Risk Stratification J. Clin. Oncol., November 1, 2006; 24(31): 5070 - 5078. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-Q. Yin, M. Kim, J.-H. Kim, G. Kong, M.-O. Lee, K.-S. Kang, B.-I. Yoon, H.-L. Kim, and B.-H. Lee Hepatic Gene Expression Profiling and Lipid Homeostasis in Mice Exposed to Steatogenic Drug, Tetracycline Toxicol. Sci., November 1, 2006; 94(1): 206 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Barth, R. Kuner, A. Buness, M. Ruschhaupt, S. Merk, L. Zwermann, S. Kaab, E. Kreuzer, G. Steinbeck, U. Mansmann, et al. Identification of a Common Gene Expression Signature in Dilated Cardiomyopathy Across Independent Microarray Studies J. Am. Coll. Cardiol., October 17, 2006; 48(8): 1610 - 1617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. S. Motakis, G. P. Nason, P. Fryzlewicz, and G. A. Rutter Variance stabilization and normalization for one-color microarray data using a data-driven multiscale approach Bioinformatics, October 15, 2006; 22(20): 2547 - 2553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Manoli, N. Gretz, H.-J. Grone, M. Kenzelmann, R. Eils, and B. Brors Group testing for pathway analysis improves comparability of different microarray datasets Bioinformatics, October 15, 2006; 22(20): 2500 - 2506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Roldo, E. Missiaglia, J. P. Hagan, M. Falconi, P. Capelli, S. Bersani, G. A. Calin, S. Volinia, C.-G. Liu, A. Scarpa, et al. MicroRNA Expression Abnormalities in Pancreatic Endocrine and Acinar Tumors Are Associated With Distinctive Pathologic Features and Clinical Behavior J. Clin. Oncol., October 10, 2006; 24(29): 4677 - 4684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. N. Moens, K. van der Ven, P. Van Remortel, J. Del-Favero, and W. M. De Coen Expression Profiling of Endocrine-Disrupting Compounds Using a Customized Cyprinus carpio cDNA Microarray Toxicol. Sci., October 1, 2006; 93(2): 298 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Saris, P. A.C. 't Hoen, I. M. Garrelds, D. H.W. Dekkers, J. T. den Dunnen, J. M.J. Lamers, and A.H. Jan Danser Prorenin Induces Intracellular Signaling in Cardiomyocytes Independently of Angiotensin II Hypertension, October 1, 2006; 48(4): 564 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Papana and H. Ishwaran CART variance stabilization and regularization for high-throughput genomic data Bioinformatics, September 15, 2006; 22(18): 2254 - 2261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Huber, J. Toedling, and L. M. Steinmetz Transcript mapping with high-density oligonucleotide tiling arrays Bioinformatics, August 15, 2006; 22(16): 1963 - 1970. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kirschner-Schwabe, C. Lottaz, J. Todling, P. Rhein, L. Karawajew, C. Eckert, A. von Stackelberg, U. Ungethum, D. Kostka, A. E. Kulozik, et al. Expression of Late Cell Cycle Genes and an Increased Proliferative Capacity Characterize Very Early Relapse of Childhood Acute Lymphoblastic Leukemia Clin. Cancer Res., August 1, 2006; 12(15): 4553 - 4561. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Lee, D.-H. Jun, C.-I. Hwang, S. S. Park, J. J. Kang, H.-S. Park, J. Kim, J. H. Kim, J.-S. Seo, and W.-Y. Park Selection of Neural Differentiation-Specific Genes by Comparing Profiles of Random Differentiation Stem Cells, August 1, 2006; 24(8): 1946 - 1955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sundaresh, D. L. Doolan, S. Hirst, Y. Mu, B. Unal, D. H. Davies, P. L. Felgner, and P. Baldi Identification of humoral immune responses in protein microarrays using DNA microarray data analysis techniques Bioinformatics, July 15, 2006; 22(14): 1760 - 1766. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hummel, S. Bentink, H. Berger, W. Klapper, S. Wessendorf, T. F.E. Barth, H.-W. Bernd, S. B. Cogliatti, J. Dierlamm, A. C. Feller, et al. A biologic definition of Burkitt's lymphoma from transcriptional and genomic profiling. N. Engl. J. Med., June 8, 2006; 354(23): 2419 - 2430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Steinhoff and M. Vingron Normalization and quantification of differential expression in gene expression microarrays Brief Bioinform, June 1, 2006; 7(2): 166 - 177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bauer, J. D. Katzenberger, A. C. Hamm, M. Bonaus, I. Zinke, J. Jaekel, and M. J. Pankratz Purine and folate metabolism as a potential target of sex-specific nutrient allocation in Drosophila and its implication for lifespan-reproduction tradeoff Physiol Genomics, May 16, 2006; 25(3): 393 - 404. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Engelen, B. Naudts, B. De Moor, and K. Marchal A calibration method for estimating absolute expression levels from microarray data Bioinformatics, May 15, 2006; 22(10): 1251 - 1258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. David, W. Huber, M. Granovskaia, J. Toedling, C. J. Palm, L. Bofkin, T. Jones, R. W. Davis, and L. M. Steinmetz A high-resolution map of transcription in the yeast genome PNAS, April 4, 2006; 103(14): 5320 - 5325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Irizarry, Z. Wu, and H. A. Jaffee Comparison of Affymetrix GeneChip expression measures Bioinformatics, April 1, 2006; 22(7): 789 - 794. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rattray, X. Liu, G. Sanguinetti, M. Milo, and N. D. Lawrence Propagating uncertainty in microarray data analysis Brief Bioinform, March 1, 2006; 7(1): 37 - 47.
|
|
|
|
|
|
J. Cardoso, L. Molenaar, R. X. de Menezes, M. van Leerdam, C. Rosenberg, G. Moslein, J. Sampson, H. Morreau, J. M. Boer, and R. Fodde Chromosomal Instability in MYH- and APC-Mutant Adenomatous Polyps. Cancer Res., March 1, 2006; 66(5): 2514 - 2519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
|