Significance tests for analyzing gene expression data with small sample sizes

Journal article

Ullah, Insha, Paul, Sudhir, Hong, Zhenjie and Wang, You-Gan. (2019). Significance tests for analyzing gene expression data with small sample sizes. Bioinformatics. 35(20), pp. 3996-4003. https://doi.org/10.1093/bioinformatics/btz189
AuthorsUllah, Insha, Paul, Sudhir, Hong, Zhenjie and Wang, You-Gan
Abstract

Motivation: Under two biologically different conditions, we are often interested in identifying differentially expressed genes. It is usually the case that the assumption of equal variances on the two groups is violated for many genes where a large number of them are required to be filtered or ranked. In these cases, exact tests are unavailable and the Welch's approximate test is most reliable one. The Welch's test involves two layers of approximations: approximating the distribution of the statistic by a t-distribution, which in turn depends on approximate degrees of freedom. This study attempts to improve upon Welch's approximate test by avoiding one layer of approximation.

Results: We introduce a new distribution that generalizes the t-distribution and propose a Monte Carlo based test that uses only one layer of approximation for statistical inferences. Experimental results based on extensive simulation studies show that the Monte Carol based tests enhance the statistical power and performs better than Welch's t-approximation, especially when the equal variance assumption is not met and the sample size of the sample with a larger variance is smaller. We analyzed two gene-expression datasets, namely the childhood acute lymphoblastic leukemia gene-expression dataset with 22 283 genes and Golden Spike dataset produced by a controlled experiment with 13 966 genes. The new test identified additional genes of interest in both datasets. Some of these genes have been proven to play important roles in medical literature.

Availability and implementation: R scripts and the R package mcBFtest is available in CRAN and to reproduce all reported results are available at the GitHub repository, https://github.com/iullah1980/MCTcodes.

Supplementary information: Supplementary data is available at Bioinformatics online.

KeywordsBiometry; Gene Expression; Monte Carlo Method; Sample Size; Statistical Distributions
Year01 Jan 2019
JournalBioinformatics
Journal citation35 (20), pp. 3996-4003
PublisherOxford University Press
ISSN1367-4803
Digital Object Identifier (DOI)https://doi.org/10.1093/bioinformatics/btz189
PubMed ID30874796
Web address (URL)https://academic.oup.com/bioinformatics/article/35/20/3996/5381541
Open accessPublished as non-open access
Research or scholarlyResearch
Page range3996-4003
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Output statusPublished
Publication dates
Online15 Mar 2019
Publication process dates
Accepted13 Mar 2019
Deposited11 Jan 2023
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© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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Place of publicationUnited Kingdom
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Xu, Ancha, Wang, You-Gan, Zheng, Shurong and Cai, Fengjing. (2020). Bias reduction in the two-stage method for degradation data analysis. Applied Mathematical Modelling. 77(Part 2), pp. 1413-1424. https://doi.org/10.1016/j.apm.2019.08.024
Exact algorithms for energy-efficient virtual machine placement in data centers
Wei, Chen, Hu, Zhi-Hua and Wang, You-Gan. (2020). Exact algorithms for energy-efficient virtual machine placement in data centers. Future Generation Computer Systems. 106, pp. 77-91. https://doi.org/10.1016/j.future.2019.12.043
A working likelihood approach for robust regression
Fu, Liya, Wang, You-Gan and Cai, Fengjing. (2020). A working likelihood approach for robust regression. Statistical Methods in Medical Research. 29(12), pp. 3641-3652. https://doi.org/10.1177/0962280220936310
Maritime convection and fluctuation between Vietnam and China : A data-driven study
Hu, Zhi-Hua, Liu, Chan-Juan, Chen, Wanting, Wang, You-Gan and Wei, Chen. (2020). Maritime convection and fluctuation between Vietnam and China : A data-driven study. Research in Transportation Business and Management. 34, pp. 1-15. https://doi.org/10.1016/j.rtbm.2019.100414
Identifying barley pan-genome sequence anchors using genetic mapping and machine learning
Gao, Shang, Wu, Ryan, Stiller, Jiri, Zheng, Zhi, Zhou, Meixue, Wang, You-Gan and Liu, Chunji. (2020). Identifying barley pan-genome sequence anchors using genetic mapping and machine learning. Theoretical and Applied Genetics. 133(9), pp. 2535-2544. https://doi.org/10.1007/s00122-020-03615-y
Natural mortality estimation using tree-based ensemble learning models
Liu, Chanjuan, Zhou, Shijie, Wang, You-Gan and Hu, Zhi-Hua. (2020). Natural mortality estimation using tree-based ensemble learning models. ICES Journal of Marine Science. 77(4), pp. 1414-1426. https://doi.org/10.1093/icesjms/fsaa058
Profile-guided three-phase virtual resource management for energy efficiency of data centers
Ding, Zhe, Tian, Yu-Chu, Tang, Maolin, Li, Yuefeng, Wang, You-Gan and Zhou, Chunjie. (2020). Profile-guided three-phase virtual resource management for energy efficiency of data centers. IEEE Transactions on Industrial Electronics. 67(3), pp. 2460-2468. https://doi.org/10.1109/TIE.2019.2902786
Response of water quality to land use and sewage outfalls in different seasons
Xu, Jing, Jin, Guangqiu, Tang, Hongwu, Mo, Yuming, Wang, You-Gan and Li, Ling. (2019). Response of water quality to land use and sewage outfalls in different seasons. Science of the Total Environment. 696, p. Article 134014. https://doi.org/10.1016/j.scitotenv.2019.134014
A new hybrid model to predict the electrical load in five states of Australia
Wu, Jinran, Cui, Zhesen, Chen, Yanyan, Kong, Demeng and Wang, You-Gan. (2019). A new hybrid model to predict the electrical load in five states of Australia. Energy. 166, pp. 598-609. https://doi.org/10.1016/j.energy.2018.10.076
Sweepstakes reproductive success is absent in a New Zealand snapper (Chrysophrus auratus) population protected from fishing despite “tiny” Ne/N ratios elsewhere
Jones, Andy, Lavery, Shane D., Le Port, Agnès, Wang, You-Gan, Blower, Dean and Ovenden, Jennifer. (2019). Sweepstakes reproductive success is absent in a New Zealand snapper (Chrysophrus auratus) population protected from fishing despite “tiny” Ne/N ratios elsewhere. Molecular Ecology. 28(12), pp. 2986-2995. https://doi.org/10.1111/mec.15130
A review of the Behrens–Fisher problem and some of its analogs : Does the same size fit all?
Paul, Sudhir, Wang, You-Gan and Ullah, Insha. (2019). A review of the Behrens–Fisher problem and some of its analogs : Does the same size fit all? Revstat Statistical Journal. 17(4), p. 563–597.
Incorporating social objectives in evaluating sustainable fisheries harvest strategy
Wu, Jiafeng, Wang, Na, Hu, Zhi-Hua, Hong, Zhenjie and Wang, You-Gan. (2019). Incorporating social objectives in evaluating sustainable fisheries harvest strategy. Environmental Modeling and Assessment. 24(4), pp. 381-386. https://doi.org/10.1007/s10666-019-9651-9
Robust Estimation Using Modified Huber’s Functions With New Tails
Jiang, Yunlu, Wang, You-Gan, Fu, Liya and Wang, Xueqin. (2019). Robust Estimation Using Modified Huber’s Functions With New Tails. Technometrics. 61(1), pp. 111-122. https://doi.org/10.1080/00401706.2018.1470037
Variable selection in rank regression for analyzing longitudinal data
Fu, Liya and Wang, You-Gan. (2018). Variable selection in rank regression for analyzing longitudinal data. Statistical Methods in Medical Research. 27(8), pp. 2447-2458. https://doi.org/10.1177/0962280216681347
Assessing temporal variations of Ammonia Nitrogen concentrations and loads in the Huaihe River Basin in relation to policies on pollution source control
Xu, Jing, Jin, Guangqiu, Tang, Hongwu, Zhang, Pei, Wang, Shen, Wang, You-Gan and Li, Ling. (2018). Assessing temporal variations of Ammonia Nitrogen concentrations and loads in the Huaihe River Basin in relation to policies on pollution source control. Science of the Total Environment. 642, pp. 1386-1395. https://doi.org/10.1016/j.scitotenv.2018.05.395
Genomic prediction of breeding values using a subset of SNPs identified by three machine learning methods
Li, Bo, Zhang, Nanxi, Wang, You-Gan, George, Andrew W., Reverter, Antonio and Li, Yutao. (2018). Genomic prediction of breeding values using a subset of SNPs identified by three machine learning methods. Frontiers in Genetics. 9, p. Article 237. https://doi.org/10.3389/fgene.2018.00237
Dividend growth and equity premium predictability
Zhu, Min, Chen, Rui, Du, Ke and Wang, You-Gan. (2018). Dividend growth and equity premium predictability. International Review of Economics and Finance. 56, pp. 125-137. https://doi.org/10.1016/j.iref.2017.10.020
Robust Regression with Data-Dependent Regularization Parameters and Autoregressive Temporal Correlations
Wang, Na, Wang, You-Gan, Hu, Shuwen, Hu, Zhi-Hua, Xu, Jing, Tang, Hongwu and Jin, Guangqiu. (2018). Robust Regression with Data-Dependent Regularization Parameters and Autoregressive Temporal Correlations. Environmental Modeling and Assessment. 23(6), pp. 779-786. https://doi.org/10.1007/s10666-018-9605-7
Analysis of spatial data with a nested correlation structure
Adegboye, Oyelola, Leung, Denis and Wang, You-Gan. (2018). Analysis of spatial data with a nested correlation structure. Journal of the Royal Statistical Society Series C: Applied Statistics. 67(2), pp. 329-354. https://doi.org/10.1111/rssc.12230
Working correlation structure selection in generalized estimating equations
Fu, Liya, Hao, Yangyang and Wang, You-Gan. (2018). Working correlation structure selection in generalized estimating equations. Computational Statistics. 33(2), pp. 983-996. https://doi.org/10.1007/s00180-018-0800-4
Selection of working correlation structure in generalized estimating equations
Wang, You-Gan and Fu, Liya. (2017). Selection of working correlation structure in generalized estimating equations. Statistics in Medicine. 36(14), pp. 2206-2219. https://doi.org/10.1002/sim.7262
Blockwise AICc for model selection in generalized linear models
Song, Guofeng, Dong, Xiaogang, Wu, Jiafeng and Wang, You-Gan. (2017). Blockwise AICc for model selection in generalized linear models. Environmental Modeling and Assessment. 22(6), pp. 523-533. https://doi.org/10.1007/s10666-017-9552-8
A comment on Koh’s “The optimal design of fallible organizations : Invariance of optimal decision threshold and uniqueness of hierarchy and polyarchy structures”
Zhu, Min, Liu, Chang and Wang, You-Gan. (2017). A comment on Koh’s “The optimal design of fallible organizations : Invariance of optimal decision threshold and uniqueness of hierarchy and polyarchy structures”. Social Choice and Welfare. 48(2), pp. 385-392. https://doi.org/10.1007/s00355-016-1009-5
The Buckley–James estimator and induced smoothing
Wang, You-Gan, Zhao, Yudong and Fu, Liya. (2016). The Buckley–James estimator and induced smoothing. Australian and New Zealand Journal of Statistics. 58(2), pp. 211-225. https://doi.org/10.1111/anzs.12155
Maximum likelihood estimation of natural mortality and quantification of temperature effects on catchability of brown tiger prawn (penaeus esculentus) in Moreton Bay (Australia) using logbook data
Kienzle, Marco, Sterling, David, Zhou, Shijie and Wang, You-Gan. (2016). Maximum likelihood estimation of natural mortality and quantification of temperature effects on catchability of brown tiger prawn (penaeus esculentus) in Moreton Bay (Australia) using logbook data. Ecological Modelling. 322, pp. 1-9. https://doi.org/10.1016/j.ecolmodel.2015.11.008
Otolith morphology of four mackerel species (Scomberomorus spp.) in Australia : Species differentiation and prediction for fisheries monitoring and assessment
Zischke, Mitchell T., Litherland, Lenore, Tilyard, Benjamin R., Stratford, Nicholas J., Jones, Ebony L. and Wang, You-Gan. (2016). Otolith morphology of four mackerel species (Scomberomorus spp.) in Australia : Species differentiation and prediction for fisheries monitoring and assessment. Fisheries Research. 176, pp. 39-47. https://doi.org/10.1016/j.fishres.2015.12.003
Efficient parameter estimation via Gaussian copulas for quantile regression with longitudinal data
Fu, Liya and Wang, You-Gan. (2016). Efficient parameter estimation via Gaussian copulas for quantile regression with longitudinal data. Journal of Multivariate Analysis. 143, pp. 492-502. https://doi.org/10.1016/j.jmva.2015.07.004
Mixture of time-dependent growth models with an application to blue swimmer crab length-frequency data
Lloyd-Jones, Luke R., Nguyen, Hien D., McLachlan, Geoffrey J., Sumpton, Wayne and Wang, You-Gan. (2016). Mixture of time-dependent growth models with an application to blue swimmer crab length-frequency data. Biometrics. 72(4), pp. 1255-1265. https://doi.org/10.1111/biom.12531
Movement and growth of the coral reef holothuroids Bohadschia argus and Thelenota ananas
Purcell, Steven W., Piddocke, Toby P., Dalton, Steven J. and Wang, You-Gan. (2016). Movement and growth of the coral reef holothuroids Bohadschia argus and Thelenota ananas. Marine Ecology Progress Series. 551, pp. 201-214. https://doi.org/10.3354/meps11720
Improved confidence intervals for the linkage disequilibrium method for estimating effective population size
Jones, A. T., Ovenden, J. R. and Wang, Y.-G.. (2016). Improved confidence intervals for the linkage disequilibrium method for estimating effective population size. Heredity. 117(4), pp. 217-223. https://doi.org/10.1038/hdy.2016.19