Chebyshev’s Inequality for Nonparametric Testing with Small N and α in Microarray Research
Abstract
Summary: Microarrays are a powerful new technology that allow for the measurement of the expression of thousands of genes simultaneously. Owing to relatively high costs, sample sizes tend to be quite small. If investigators apply a correction for multiple testing, a very small p-value will be required to declare significance. We use modifications to Chebyshev’s inequality to develop a testing procedure that is nonparametric and yields p-values on the interval [0, 1]. We evaluate its properties via simulation and show that it both holds the type I error rate below nominal levels in almost all conditions and can yield p-values denoting significance even with very small sample sizes and stringent corrections for multiple testing.
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When the number of clusters, K, per treatment group is small, the maximum number of different bootstrap samples is also small, resulting in a problem of a limited number of 'distinct' p-values.
“When the number of clusters, K, per treatment group is small, the maximum number of different bootstrap samples is also small, resulting in a problem of a limited number of “distinct” p-values [31].”
Cites
An Introduction to the Bootstrap
Efron, B., & Tibshirani, R. J. (1994) · doi:10.1201/9780429246593 · Cited by 40,500 · see citing works
An Introduction to the Bootstrap
Efron, B., & Tibshirani, R. J. (1993) · doi:10.1007/978-1-4899-4541-9 · Cited by 21,230 · see citing works
In silico prediction of protein-protein interactions in human macrophages
Souiai, O., Guerfali, F. Z., Miled, S. B., Brun, C., & Benkahla, A. (2014) · BMC Research Notes · doi:10.1186/1756-0500-7-157 · Cited by 10,785 · see citing works
Significance analysis of microarrays applied to the ionizing radiation response
Tusher, V. G., Tibshirani, R., & Chu, G. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.091062498 · Cited by 10,568 · see citing works
Scheffé, H. (1960) · Soil Science · doi:10.1097/00010694-196006000-00016 · Cited by 5,625 · see citing works
Multiple comparisons among means
Dunn, O. J. (1961) · Journal of the American Statistical Association · doi:10.1080/01621459.1961.10482090 · Cited by 5,006 · see citing works
An Approximate Distribution of Estimates of Variance Components
Satterthwaite, F. E. (1946) · Biometrics Bulletin · doi:10.2307/3002019 · Cited by 4,373 · see citing works
Rectangular Confidence Regions for the Means of Multivariate Normal Distributions
Šidák, Z. (1967) · Journal of the American Statistical Association · doi:10.1080/01621459.1967.10482935 · Cited by 2,904 · see citing works
Introduction to Robust Estimation and Hypothesis Testing
Wilcox, R. R. (2012) · Elsevier eBooks · doi:10.1016/c2010-0-67044-1 · Cited by 2,086 · see citing works
Distribution-Free Statistical Tests
Bell, C. B. (1970) · Technometrics · doi:10.1080/00401706.1970.10488744 · Cited by 1,699 · see citing works
Dominance statistics: Ordinal analyses to answer ordinal questions.
Cliff, N. (1993) · Psychological Bulletin · doi:10.1037/0033-2909.114.3.494 · Cited by 1,542 · see citing works
Rectangular Confidence Regions for the Means of Multivariate Normal Distributions
Šidák, Z. (1967) · Journal of the American Statistical Association · doi:10.2307/2283989 · Cited by 1,455 · see citing works
Permutation Tests: A Practical Guide to Resampling Methods for Testing Hypotheses
Niknian, M., & Good, P. (1995) · Technometrics · doi:10.2307/1269919 · Cited by 1,406 · see citing works
On the adaptive control of the false discovery rate in multiple testing with independent statistics
Benjamini, Y., & Hochberg, Y. (2000) · Journal of Educational and Behavioral Statistics · doi:10.3102/10769986025001060 · Cited by 1,349 · see citing works
Gene-expression profile of the ageing brain in mice
Lee, C.-K., Weindruch, R., & Prolla, T. A. (2000) · Nature Genetics · doi:10.1038/77046 · Cited by 1,055 · see citing works
Distribution-Free Statistical Tests.
Gastwirth, J. L., & Bradley, J. V. (1969) · Journal of the American Statistical Association · doi:10.2307/2283492 · Cited by 1,002 · see citing works
The effects of violations of assumptions underlying the t test.
Boneau, C. A. (1960) · Psychological Bulletin · doi:10.1037/h0041412 · Cited by 791 · see citing works
Bradley, J. V. (1978) · British Journal of Mathematical and Statistical Psychology · doi:10.1111/j.2044-8317.1978.tb00581.x · Cited by 743 · see citing works
Empirical Bayes methods and false discovery rates for microarrays
Efron, B., & Tibshirani, R. (2002) · Genetic Epidemiology · doi:10.1002/gepi.1124 · Cited by 684 · see citing works
The Nonparametric Behrens-Fisher Problem: Asymptotic Theory and a Small-Sample Approximation
Brunner, E., & Munzel, U. (2000) · Biometrical Journal · doi:10.1002/(sici)1521-4036(200001)42:1 · Cited by 630 · see citing works
Good, P. (2000) · Springer series in statistics · doi:10.1007/978-1-4757-3235-1 · Cited by 578 · see citing works
Statistical design and the analysis of gene expression microarray data
Kerr, K. F., & Churchill, G. A. (2007) · Genetics Research · doi:10.1017/s0016672308009713 · Cited by 559 · see citing works
Introduction to Robust Estimation and Hypothesis Testing
Horn, P. S., & Wilcox, R. R. (1998) · Technometrics · doi:10.2307/1271402 · Cited by 521 · see citing works
Statistical design and the analysis of gene expression microarray data
Kerr, K. F., & Churchill, G. A. (2001) · Genetics Research · doi:10.1017/s0016672301005055 · Cited by 482 · see citing works
Kayo, T., Allison, D. B., Weindruch, R., & Prolla, T. A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.081061898 · Cited by 384 · see citing works
Self-citationIdentification of differentially expressed genes in pancreatic cancer cells using cDNA microarray.
Han, H., Bearss, D. J., Browne, L. W., Calaluce, R., Nagle, R. B., & Hoff, D. D. V. (2002) · PubMed · Cited by 380 · see citing works
A mixture model approach for the analysis of microarray gene expression data
Allison, D. B., Gadbury, G. L., Heo, M., Fernández, J. R., Lee, C., Prolla, T. A., & Weindruch, R. H. (2002) · Computational Statistics & Data Analysis · doi:10.1016/s0167-9473(01)00046-9 · Cited by 358 · see citing works
Self-citationHow to Use the Two Sample t‐Test
Cressie, N., & Whitford, H. J. (1986) · Biometrical Journal · doi:10.1002/bimj.4710280202 · Cited by 222 · see citing works
Chebyshev Inequality with Estimated Mean and Variance
Saw, J. G., Yang, M. C. K., & Mo, T. C. (1984) · The American Statistician · doi:10.1080/00031305.1984.10483182 · Cited by 210 · see citing works
Karian, Z. A., & Dudewicz, E. J. (2019) · Thammasat University Digital Collections · Cited by 203 · see citing works
Microarrays in ecology and evolution: a preview
Gibson, G. C. (2002) · Molecular Ecology · doi:10.1046/j.0962-1083.2001.01425.x · Cited by 192 · see citing works
Chasing the dream: plant EST microarrays
Richmond, T., & Somerville, S. C. (2000) · Current Opinion in Plant Biology · doi:10.1016/s1369-5266(99)00049-7 · Cited by 185 · see citing works
Fitting Statistical Distributions
Karian, Z. A., & Dudewicz, E. J. (2000) · Chapman & Hall/CRC eBooks · doi:10.1201/9781420038040 · Cited by 179 · see citing works
ERBB2 up-regulates S100A4 and several other prometastatic genes in medulloblastoma.
Hernán, R., Fasheh, R., Calabrese, C. R., Frank, A. J., Maclean, K. H., Allard, D., Barraclough, R., & Gilbertson, R. J. (2003) · PubMed · Cited by 170 · see citing works
Chen, C., Li, M., de Graaf, D., Monti, S., Göttgens, B., Sánchez, M. J., Lander, E. S., Golub, T. R., Green, A. R., & Lodish, H. F. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.202614899 · Cited by 167 · see citing works
DNA Microarray Analysis of Genes Differentially Expressed in Diet‐Induced (Cafeteria) Obese Rats
López, I. P., Martí, A., Milagro, F. I., Zulet, M. Á., Moreno-Aliaga, M. J., Martínez, J. A., & de Miguel, C. (2003) · Obesity Research · doi:10.1038/oby.2003.30 · Cited by 154 · see citing works
Robustness to non-normality of regression tests
BOX, G. E. P., & WATSON, G. S. (1962) · Biometrika · doi:10.1093/biomet/49.1-2.93 · Cited by 149 · see citing works
Sustained Expression of Homeobox D10 Inhibits Angiogenesis
Myers, C. A., Charboneau, A. L., Cheung, I., Hanks, D. K., & Boudreau, N. J. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64488-4 · Cited by 147 · see citing works
Li, W., Liang, X., Leu, J. I., Kovalovich, K., Ciliberto, G., & Taub, R. (2001) · Hepatology · doi:10.1053/jhep.2001.24431 · Cited by 114 · see citing works
DNA array profiling of gene expression changes during maize embryo development
Lee, J.-M., Williams, M. E., Tingey, S. V., et al. (2002) · Functional & Integrative Genomics · doi:10.1007/s10142-002-0046-6 · Cited by 90 · see citing works
Algina, J. J., Oshima, T. C., & Lin, W.-Y. (1994) · Journal of Educational and Behavioral Statistics · doi:10.3102/10769986019003275 · Cited by 76 · see citing works
Discovery and analysis of hepatocellular carcinoma genes using cDNA microarrays
Li, Y., Li, Y., Tang, R., et al. (2002) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-002-0347-0 · Cited by 70 · see citing works
Miyazawa, K., Mori, A., Yamamoto, K., & Okudaira, H. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.13.7620 · Cited by 69 · see citing works
MONTE CARLO COMPARISON OF FOUR NORMALITY TESTS USING DIFFERENT ENTROPY ESTIMATES
Esteban, M. D., Castellanos, M. E., Morales, D., et al. (2001) · Communications in Statistics - Simulation and Computation · doi:10.1081/sac-100107780 · Cited by 63 · see citing works
Generalizations of Tchebycheff’s Inequalities
Mallows, C. L. (1956) · Journal of the Royal Statistical Society Series B (Statistical Methodology) · doi:10.1111/j.2517-6161.1956.tb00220.x · Cited by 54 · see citing works
DNA Microarray Profiling to Identify Angiotensin-Responsive Genes in Vascular Smooth Muscle Cells
Campos, A. H., Zhao, Y., Pollman, M. J., et al. (2003) · Circulation Research · doi:10.1161/01.res.0000049100.22673.f6 · Cited by 52 · see citing works
The Behavior of Some Standard Statistical Tests under Nonstandard Conditions
Hotelling, H. (1961) · NCSU Libraries Repository (North Carolina State University Libraries) · Cited by 51 · see citing works
Combinatorics, computer algebra and the Wilcoxon-Mann-Whitney test
Bucchianico, A. D. (1999) · Journal of Statistical Planning and Inference · doi:10.1016/s0378-3758(98)00261-4 · Cited by 40 · see citing works
A Note on Homogeneity of Variance of Scores and Ranks
Zimmerman, D. W. (1996) · The Journal of Experimental Education · doi:10.1080/00220973.1996.10806603 · Cited by 35 · see citing works
Apoptosis and rheumatoid arthritis: Past, present, and future directions
Mountz, J. D., Hsu, H., Matsuki, Y., & Zhang, H. (2001) · Current Rheumatology Reports · doi:10.1007/s11926-001-0053-y · Cited by 32 · see citing works
Self-citationNeel, J. V., Julius, S., Weder, A. B., Yamada, M., Kardia, S. L. R., & Haviland, M. B. (1998) · Genetic Epidemiology · doi:10.1002/(sici)1098-2272(1998)15:1 · Cited by 30 · see citing works
The validity of genetic models underlying quantitative traits
Goddard, M. E. (2001) · Livestock Production Science · doi:10.1016/s0301-6226(01)00272-x · Cited by 29 · see citing works
Phadtare, S., Kato, I., & Inouye, M. (2002) · Journal of Bacteriology · doi:10.1128/jb.184.23.6725-6729.2002 · Cited by 27 · see citing works
Corominola, H., Conner, L. J., Beavers, L. S., Gadski, R. A., Johnson, D., Caro, J. F., & Rafaeloff-Phail, R. (2001) · Diabetes · doi:10.2337/diabetes.50.12.2822 · Cited by 25 · see citing works
Chebyshev Inequality with Estimated Mean and Variance
Saw, J. G., Yang, M. C. K., & Mo, T. C. (1984) · The American Statistician · doi:10.2307/2683249 · Cited by 25 · see citing works
The immune system and gene expression microarrays - new answers to old questions
Glynne, R. J., & Watson, S. R. (2001) · The Journal of Pathology · doi:10.1002/1096-9896(200109)195:1 · Cited by 24 · see citing works
Regulation of Apoptosis of Synovial Fibroblasts
Mountz, J. D., & Zhang, H.-G. (2000) · KARGER eBooks · doi:10.1159/000060524 · Cited by 23 · see citing works
Self-citationBest constants in Chebyshev inequalities with various applications
Dasgupta, A. (2000) · Metrika · doi:10.1007/s184-000-8316-9 · Cited by 18 · see citing works
Two-Stage Testing in Microarray Analysis: What Is Gained?
Allison, D. B., & Coffey, C. S. (2002) · The Journals of Gerontology Series A · doi:10.1093/gerona/57.5.b189 · Cited by 18 · see citing works
Self-citationAlgina, J. J., Oshima, T. C., & Lin, W.-Y. (1994) · Journal of Educational and Behavioral Statistics · doi:10.2307/1165297 · Cited by 18 · see citing works
Wilcox, R. R. (1993) · Cited by 16 · see citing works
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Self-citation
- Authors
- Beasley, T. M., Page, G. P., Brand, J. P. L., Gadbury, G. L., Mountz, J. D., & Allison, D. B.
- Affiliations
- University of Alabama at Birmingham (US)
- Missouri University of Science and Technology (US)
- Corresponding author
- Beasley, T. Mark
- Venue
- Journal of the Royal Statistical Society Series C: Applied Statistics
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-01-01
- Volume
- 53
- Issue
- 1
- Pages
- 95-108
- ISSN
- 0035-9254 (ISSN-L)
- 1467-9876
- OpenAlex
- W2158417484
- Cited by
- 15
- References
- 61
- Citations by year
- 2024: 1 · 2022: 1 · 2021: 1 · 2019: 1 · 2018: 1 · 2016: 2 · 2014: 1 · 2012: 1
- FWCI
- 0.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of the Royal Statistical Society Series C (Applied Statistics) (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Physical Sciences › Mathematics › Statistics and Probability › Probability and Statistical Research
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Keywords
- Chebyshev inequality, nonparametric tests, microarray data, gene expression, small sample size, multiple testing correction, p-values, type I error rate, significance testing
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