Nucleic Acids Research, 2002, Vol. 30, No. 4 e15
© 2002 Oxford University Press
Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation
1Department of Statistics, 2Division of Biostatistics, 3Department of Molecular and Cell Biology, 4Functional Genomics Laboratory and 5Neurogenomics Center, Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720-3860, USA and 6Division of Genetics and Bioinformatics, The Walter and Eliza Hall Institute, Melbourne, Australia
There are many sources of systematic variation in cDNA microarray experiments which affect the measured gene expression levels (e.g. differences in labeling efficiency between the two fluorescent dyes). The term normalization refers to the process of removing such variation. A constant adjustment is often used to force the distribution of the intensity log ratios to have a median of zero for each slide. However, such global normalization approaches are not adequate in situations where dye biases can depend on spot overall intensity and/or spatial location within the array. This article proposes normalization methods that are based on robust local regression and account for intensity and spatial dependence in dye biases for different types of cDNA microarray experiments. The selection of appropriate controls for normalization is discussed and a novel set of controls (microarray sample pool, MSP) is introduced to aid in intensity-dependent normalization. Lastly, to allow for comparisons of expression levels across slides, a robust method based on maximum likelihood estimation is proposed to adjust for scale differences among slides.
* To whom correspondence should be addressed at: Department of Statistics, University of California, 367 Evans Hall, #3860 Berkeley, CA 94720-3860, USA. Tel: +1 510 642 2781; Fax: +1 510 642 7892; Email: terry{at}stat.berkeley.eduThe authors wish it to be known that, in their opinion, the first three authors should be regarded as joint First Authors
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R. B. Scharpf, C. A. Iacobuzio-Donahue, J. B. Sneddon, and G. Parmigiani When should one subtract background fluorescence in 2-color microarrays? Biostat., October 1, 2007; 8(4): 695 - 707. [Abstract] [Full Text] [PDF] |
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J. Davidsson, A. Andersson, K. Paulsson, M. Heidenblad, M. Isaksson, A. Borg, J. Heldrup, M. Behrendtz, I. Panagopoulos, T. Fioretos, et al. Tiling resolution array comparative genomic hybridization, expression and methylation analyses of dup(1q) in Burkitt lymphomas and pediatric high hyperdiploid acute lymphoblastic leukemias reveal clustered near-centromeric breakpoints and overexpression of genes in 1q22-32.3 Hum. Mol. Genet., September 15, 2007; 16(18): 2215 - 2225. [Abstract] [Full Text] [PDF] |
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C Espinoza, C Medina, S Somerville, and P Arce-Johnson Senescence-associated genes induced during compatible viral interactions with grapevine and Arabidopsis J. Exp. Bot., September 4, 2007; (2007) erm165v2. [Abstract] [Full Text] [PDF] |
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J. H. Kim, S. M. Dhanasekaran, R. Mehra, S. A. Tomlins, W. Gu, J. Yu, C. Kumar-Sinha, X. Cao, A. Dash, L. Wang, et al. Integrative Analysis of Genomic Aberrations Associated with Prostate Cancer Progression Cancer Res., September 1, 2007; 67(17): 8229 - 8239. [Abstract] [Full Text] [PDF] |
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L. Marisa, J.-L. Ichante, N. Reymond, L. Aggerbeck, H. Delacroix, and M.-H. Mucchielli-Giorgi MAnGO: an interactive R-based tool for two-colour microarray analysis Bioinformatics, September 1, 2007; 23(17): 2339 - 2341. [Abstract] [Full Text] [PDF] |
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A. Morozov, S. J. Lee, Z.-K. Zhang, V. Cimica, D. Zagzag, and G. V. Kalpana INI1 Induces Interferon Signaling and Spindle Checkpoint in Rhabdoid Tumors Clin. Cancer Res., August 15, 2007; 13(16): 4721 - 4730. [Abstract] [Full Text] [PDF] |
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Y. Zhou, C. Cras-Meneur, M. Ohsugi, G. D. Stormo, and M. Alan. Permutt A global approach to identify differentially expressed genes in cDNA (two-color) microarray experiments Bioinformatics, August 15, 2007; 23(16): 2073 - 2079. [Abstract] [Full Text] [PDF] |
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L. Knoops, R. Haas, S. de Kemp, D. Majoor, A. Broeks, E. Eldering, J. P. de Boer, M. Verheij, C. van Ostrom, A. de Vries, et al. In vivo p53 response and immune reaction underlie highly effective low-dose radiotherapy in follicular lymphoma Blood, August 15, 2007; 110(4): 1116 - 1122. [Abstract] [Full Text] [PDF] |
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M. Cuadros, S. S. Dave, E. S. Jaffe, E. Honrado, R. Milne, J. Alves, J. Rodriguez, M. Zajac, J. Benitez, L. M. Staudt, et al. Identification of a Proliferation Signature Related to Survival in Nodal Peripheral T-Cell Lymphomas J. Clin. Oncol., August 1, 2007; 25(22): 3321 - 3329. [Abstract] [Full Text] [PDF] |
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D. Wang, H.-M. Sung, T.-Y. Wang, C.-J. Huang, P. Yang, T. Chang, Y.-C. Wang, D.-L. Tseng, J.-P. Wu, T.-C. Lee, et al. Expression evolution in yeast genes of single-input modules is mainly due to changes in trans-acting factors Genome Res., August 1, 2007; 17(8): 1161 - 1169. [Abstract] [Full Text] [PDF] |
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B. Asselbergh, K. Curvers, S. C. Franca, K. Audenaert, M. Vuylsteke, F. Van Breusegem, and M. Hofte Resistance to Botrytis cinerea in sitiens, an Abscisic Acid-Deficient Tomato Mutant, Involves Timely Production of Hydrogen Peroxide and Cell Wall Modifications in the Epidermis Plant Physiology, August 1, 2007; 144(4): 1863 - 1877. [Abstract] [Full Text] [PDF] |
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S. Rottenberg, A. O. H. Nygren, M. Pajic, F. W. B. van Leeuwen, I. van der Heijden, K. van de Wetering, X. Liu, K. E. de Visser, K. G. Gilhuijs, O. van Tellingen, et al. Selective induction of chemotherapy resistance of mammary tumors in a conditional mouse model for hereditary breast cancer PNAS, July 17, 2007; 104(29): 12117 - 12122. [Abstract] [Full Text] [PDF] |
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K. T. Pilobello, D. E. Slawek, and L. K. Mahal A ratiometric lectin microarray approach to analysis of the dynamic mammalian glycome PNAS, July 10, 2007; 104(28): 11534 - 11539. [Abstract] [Full Text] [PDF] |
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D. Stygar, B. Masironi, H. Eriksson, and L. Sahlin Studies on estrogen receptor (ER) {alpha} and {beta} responses on gene regulation in peripheral blood leukocytes in vivo using selective ER agonists J. Endocrinol., July 1, 2007; 194(1): 101 - 119. [Abstract] [Full Text] [PDF] |
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