Bioinformatics Vol. 18 no. 9 2002
Pages 1207-1215
© 2002 Oxford University Press
Ratio statistics of gene expression levels and applications to microarray data analysis
1 Cancer Genetics Branch, National Human Genome Research Institute,
National Institutes of Health, Building 50, Room 5154,
50 South Drive, MSC 8000, Bethesda, MD 20892, USA
2 Department of Electrical Engineering,
Texas A&M University, 3128 TAMU, College Station, TX 77843-3128, USA
Received on November 19, 2001
; revised on March 4, 2002
; accepted on March 19, 2002
Motivation: Expression-based analysis for large families of genes has recently become possible owing to the development of cDNA microarrays, which allow simultaneous measurement of transcript levels for thousands of genes. For each spot on a microarray, signals in two channels must be extracted from their backgrounds. This requires algorithms to extract signals arising from tagged mRNA hybridized to arrayed cDNA locations and algorithms to determine the significance of signal ratios.
Results: This paper focuses on estimation of signal ratios from the two channels, and the significance of those ratios. The key issue is the determination of whether a ratio is significantly high or low in order to conclude whether the gene is upregulated or downregulated. The paper builds on an earlier study that involved a hypothesis test based on a ratio statistic under the supposition that the measured fluorescent intensities subsequent to image processing can be assumed to reflect the signal intensities. Here, a refined hypothesis test is considered in which the measured intensities forming the ratio are assumed to be combinations of signal and background. The new method involves a signal-to-noise ratio, and for a high signal-to-noise ratio the new test reduces (with close approximation) to the original test. The effect of low signal-to-noise ratio on the ratio statistics constitutes the main theme of the paper. Finally, and in this vein, a quality metric is formulated for spots. This measure can be used to decide whether or not a spot ratio should be deleted, or to adjust various measurements to reflect confidence in the quality of the measurement.
Contact: e-dougherty{at}tamu.edu
* To whom correspondence should be addressed.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Liu, M. C. Casimiro, C. Wang, L. A. Shirley, X. Jiao, S. Katiyar, X. Ju, Z. Li, Z. Yu, J. Zhou, et al. p21CIP1 attenuates Ras- and c-Myc-dependent breast tumor epithelial mesenchymal transition and cancer stem cell-like gene expression in vivo PNAS, November 10, 2009; 106(45): 19035 - 19039. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Carroll and Y. Wang Nonparametric variance estimation in the analysis of microarray data: a measurement error approach Biometrika, June 1, 2008; 95(2): 437 - 449. [Abstract] [PDF]
|
|
|
|
 |
|
 S. A. Amundson, K. T. Do, L. C. Vinikoor, R. A. Lee, C. A. Koch-Paiz, J. Ahn, M. Reimers, Y. Chen, D. A. Scudiero, J. N. Weinstein, et al. Integrating Global Gene Expression and Radiation Survival Parameters across the 60 Cell Lines of the National Cancer Institute Anticancer Drug Screen Cancer Res., January 15, 2008; 68(2): 415 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Thouennon, A. G. Elkahloun, J. Guillemot, A.-P. Gimenez-Roqueplo, J. Bertherat, A. Pierre, H. Ghzili, L. Grumolato, M. Muresan, M. Klein, et al. Identification of Potential Gene Markers and Insights into the Pathophysiology of Pheochromocytoma Malignancy J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4865 - 4872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 J. Zhang, W. Wright, D. A. Bernlohr, S. W. Cushman, and X. Chen Alterations of the classic pathway of complement in adipose tissue of obesity and insulin resistance Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1433 - E1440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Whiteford, S. Bilke, B. T. Greer, Q. Chen, T. A. Braunschweig, N. Cenacchi, J. S. Wei, M. A. Smith, P. Houghton, C. Morton, et al. Credentialing Preclinical Pediatric Xenograft Models Using Gene Expression and Tissue Microarray Analysis Cancer Res., January 1, 2007; 67(1): 32 - 40. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Li, C. Wang, X. Jiao, Y. Lu, M. Fu, A. A. Quong, C. Dye, J. Yang, M. Dai, X. Ju, et al. Cyclin D1 Regulates Cellular Migration through the Inhibition of Thrombospondin 1 and ROCK Signaling. Mol. Cell. Biol., June 1, 2006; 26(11): 4240 - 4256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Innes, A. N. Heinloth, K. G. Flores, S. O. Sieber, P. B. Deming, P. R. Bushel, W. K. Kaufmann, and R. S. Paules ATM Requirement in Gene Expression Responses to Ionizing Radiation in Human Lymphoblasts and Fibroblasts Mol. Cancer Res., March 1, 2006; 4(3): 197 - 207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.R. Hansson, Y. Chen, J. Brodszki, M. Chen, E. Hernandez-Andrade, J.M. Inman, O.A. Kozhich, I. Larsson, K. Marsal, P. Medstrand, et al. Gene expression profiling of human placentas from preeclamptic and normotensive pregnancies Mol. Hum. Reprod., March 1, 2006; 12(3): 169 - 179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Seubert, F. Xu, J. P. Graves, J. B. Collins, S. O. Sieber, R. S. Paules, D. L. Kroetz, and D. C. Zeldin Differential renal gene expression in prehypertensive and hypertensive spontaneously hypertensive rats Am J Physiol Renal Physiol, September 1, 2005; 289(3): F552 - F561. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. S. Kim, E. H. Choi, J. Khan, E. Roilides, A. Francesconi, M. Kasai, T. Sein, R. L. Schaufele, K. Sakurai, C. G. Son, et al. Expression of Genes Encoding Innate Host Defense Molecules in Normal Human Monocytes in Response to Candida albicans Infect. Immun., June 1, 2005; 73(6): 3714 - 3724. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Pal, A. Datta, A. J. Fornace Jr, M. L. Bittner, and E. R. Dougherty Boolean relationships among genes responsive to ionizing radiation in the NCI 60 ACDS Bioinformatics, April 15, 2005; 21(8): 1542 - 1549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sima, U. Braga-Neto, and E. R. Dougherty Superior feature-set ranking for small samples using bolstered error estimation Bioinformatics, April 1, 2005; 21(7): 1046 - 1054. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Mutsuga, T. Shahar, J. G. Verbalis, C. C. Xiang, M. J. Brownstein, and H. Gainer Regulation of Gene Expression in Magnocellular Neurons in Rat Supraoptic Nucleus during Sustained Hypoosmolality Endocrinology, March 1, 2005; 146(3): 1254 - 1267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ohsugi, C. Cras-Meneur, Y. Zhou, E. Bernal-Mizrachi, J. D. Johnson, D. S. Luciani, K. S. Polonsky, and M. A. Permutt Reduced Expression of the Insulin Receptor in Mouse Insulinoma (MIN6) Cells Reveals Multiple Roles of Insulin Signaling in Gene Expression, Proliferation, Insulin Content, and Secretion J. Biol. Chem., February 11, 2005; 280(6): 4992 - 5003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. de Bivort, S. Huang, and Y. Bar-Yam Dynamics of cellular level function and regulation derived from murine expression array data PNAS, December 21, 2004; 101(51): 17687 - 17692. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Xiang, E. Mezey, M. Chen, S. Key, L. Ma, and M. J. Brownstein Using DSP, a reversible cross-linker, to fix tissue sections for immunostaining, microdissection and expression profiling Nucleic Acids Res., December 16, 2004; 32(22): e185 - e185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Lu, J. Suen, C. Frias, R. Pfeiffer, M.-H. Tsai, E. Chuang, and S. L. Zeichner Dissection of the Kaposi's Sarcoma-Associated Herpesvirus Gene Expression Program by Using the Viral DNA Replication Inhibitor Cidofovir J. Virol., December 15, 2004; 78(24): 13637 - 13652. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G Eisenhofer, T-T Huynh, K Pacak, F M Brouwers, M M Walther, W M Linehan, P J Munson, M Mannelli, D S Goldstein, and A G Elkahloun Distinct gene expression profiles in norepinephrine- and epinephrine-producing hereditary and sporadic pheochromocytomas: activation of hypoxia-driven angiogenic pathways in von Hippel-Lindau syndrome Endocr. Relat. Cancer, December 1, 2004; 11(4): 897 - 911. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-P. Annereau, G. Szakacs, C. J. Tucker, A. Arciello, C. Cardarelli, J. Collins, S. Grissom, B. R. Zeeberg, W. Reinhold, J. N. Weinstein, et al. Analysis of ATP-Binding Cassette Transporter Expression in Drug-Selected Cell Lines by a Microarray Dedicated to Multidrug Resistance Mol. Pharmacol., December 1, 2004; 66(6): 1397 - 1405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Wei, B. T. Greer, F. Westermann, S. M. Steinberg, C.-G. Son, Q.-R. Chen, C. C. Whiteford, S. Bilke, A. L. Krasnoselsky, N. Cenacchi, et al. Prediction of Clinical Outcome Using Gene Expression Profiling and Artificial Neural Networks for Patients with Neuroblastoma Cancer Res., October 1, 2004; 64(19): 6883 - 6891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Amundson, M. B. Grace, C. B. McLeland, M. W. Epperly, A. Yeager, Q. Zhan, J. S. Greenberger, and A. J. Fornace Jr. Human In vivo Radiation-Induced Biomarkers: Gene Expression Changes in Radiotherapy Patients Cancer Res., September 15, 2004; 64(18): 6368 - 6371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Jacobson, D. Duggan, and G. Fischbach Neuregulin induces the expression of transcription factors and myosin heavy chains typical of muscle spindles in cultured human muscle PNAS, August 17, 2004; 101(33): 12218 - 12223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Mutsuga, T. Shahar, J. G. Verbalis, M. J. Brownstein, C. C. Xiang, R. F. Bonner, and H. Gainer Selective Gene Expression in Magnocellular Neurons in Rat Supraoptic Nucleus J. Neurosci., August 11, 2004; 24(32): 7174 - 7185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B Diosdado, M C Wapenaar, L Franke, K J Duran, M J Goerres, M Hadithi, J B A Crusius, J W R Meijer, D J Duggan, C J J Mulder, et al. A microarray screen for novel candidate genes in coeliac disease pathogenesis Gut, July 1, 2004; 53(7): 944 - 951. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N. Heinloth, R. D. Irwin, G. A. Boorman, P. Nettesheim, R. D. Fannin, S. O. Sieber, M. L. Snell, C. J. Tucker, L. Li, G. S. Travlos, et al. Gene Expression Profiling of Rat Livers Reveals Indicators of Potential Adverse Effects Toxicol. Sci., July 1, 2004; 80(1): 193 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ohsugi, C. Cras-Meneur, Y. Zhou, W. Warren, E. Bernal-Mizrachi, and M. A. Permutt Glucose and Insulin Treatment of Insulinoma Cells Results in Transcriptional Regulation of a Common Set of Genes Diabetes, June 1, 2004; 53(6): 1496 - 1508. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Brodsky, A. Leontovich, M. Shtutman, and E. Feinstein Identification and handling of artifactual gene expression profiles emerging in microarray hybridization experiments Nucleic Acids Res., March 3, 2004; 32(4): e46 - e46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. E. Cunliffe, M. Ringner, S. Bilke, R. L. Walker, J. M. Cheung, Y. Chen, and P. S. Meltzer The Gene Expression Response of Breast Cancer to Growth Regulators: Patterns and Correlation with Tumor Expression Profiles Cancer Res., November 1, 2003; 63(21): 7158 - 7166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Hewitt, B. J. Deroo, K. Hansen, J. Collins, S. Grissom, C. A. Afshari, and K. S. Korach Estrogen Receptor-Dependent Genomic Responses in the Uterus Mirror the Biphasic Physiological Response to Estrogen Mol. Endocrinol., October 1, 2003; 17(10): 2070 - 2083. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Xiang, M. Chen, L. Ma, Q. N. Phan, J. M. Inman, O. A. Kozhich, and M. J. Brownstein A new strategy to amplify degraded RNA from small tissue samples for microarray studies Nucleic Acids Res., May 1, 2003; 31(9): e53 - e53. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Hedenfalk, M. Ringner, A. Ben-Dor, Z. Yakhini, Y. Chen, G. Chebil, R. Ach, N. Loman, H. Olsson, P. Meltzer, et al. Molecular classification of familial non-BRCA1/BRCA2 breast cancer PNAS, March 4, 2003; 100(5): 2532 - 2537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-Y. E. Chuang, Y. Chen, Gadisetti, V. R. Chandramouli, J. A. Cook, D. Coffin, M.-H. Tsai, W. DeGraff, H. Yan, S. Zhao, et al. Gene Expression after Treatment with Hydrogen Peroxide, Menadione, or t-Butyl Hydroperoxide in Breast Cancer Cells Cancer Res., November 1, 2002; 62(21): 6246 - 6254. [Abstract] [Full Text] [PDF]
|
|