Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter April 24, 2023

A Bayesian model to identify multiple expression patterns with simultaneous FDR control for a multi-factor RNA-seq experiment

  • Yuanyuan Bian , Chong He and Jing Qiu EMAIL logo

Abstract

It is often of research interest to identify genes that satisfy a particular expression pattern across different conditions such as tissues, genotypes, etc. One common practice is to perform differential expression analysis for each condition separately and then take the intersection of differentially expressed (DE) genes or non-DE genes under each condition to obtain genes that satisfy a particular pattern. Such a method can lead to many false positives, especially when the desired gene expression pattern involves equivalent expression under one condition. In this paper, we apply a Bayesian partition model to identify genes of all desired patterns while simultaneously controlling their false discovery rates (FDRs). Our simulation studies show that the common practice fails to control group specific FDRs for patterns involving equivalent expression while the proposed Bayesian method simultaneously controls group specific FDRs at all settings studied. In addition, the proposed method is more powerful when the FDR of the common practice is under control for identifying patterns only involving DE genes. Our simulation studies also show that it is an inherently more challenging problem to identify patterns involving equivalent expression than patterns only involving differential expression. Therefore, larger sample sizes are required to obtain the same target power to identify the former types of patterns than the latter types of patterns.


Corresponding author: Jing Qiu, Department of Applied Economics and Statistics, University of Delaware, Newark, DE, USA, E-mail:

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was partially done with the use of the BIOMIX compute cluster at University of Delaware, which was made possible through funding from Delaware INBRE (NIGMS P20GM103446), the State of Delaware and the Delaware Biotechnology Institute.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

References

Abramowitz, M. and Stegun, I.A. (1964). Hypergeometric functions. In: Handbook of mathematical functions: with formulas, graphs, and mathematical tables, Vol. 55, chap. 15. Courier Corporation, Dover, New York, pp. 555–566.Search in Google Scholar

Bian, Y., He, C., Hou, J., Cheng, J., and Qiu, J. (2019). PairedFB: a full hierarchical Bayesian model for paired RNA-seq data with heterogeneous treatment effects. Bioinformatics 35: 787–797. https://doi.org/10.1093/bioinformatics/bty731.Search in Google Scholar PubMed PubMed Central

Choi, J., Tanaka, K., Cao, Y., Qi, Y., Qiu, J., Liang, Y., Lee, S.Y., and Stacey, G. (2014). Identification of a plant receptor for extracellular ATP. Science 343: 290–294. https://doi.org/10.1126/science.343.6168.290.Search in Google Scholar PubMed

Chung, L.M., Ferguson, J.P., Zheng, W., Qian, F., Bruno, V., Montgomery, R.R., and Zhao, H. (2013). Differential expression analysis for paired RNA-seq data. BMC Bioinf. 14: 110. https://doi.org/10.1186/1471-2105-14-110.Search in Google Scholar PubMed PubMed Central

Cui, S., Ji, T., Li, J., Cheng, J., and Qiu, J. (2016). What if we ignore the random effects when analyzing RNA-seq data in a multifactor experiment. Stat. Appl. Genet. Mol. Biol. 15: 87–105. https://doi.org/10.1515/sagmb-2015-0011.Search in Google Scholar PubMed

Eddelbuettel, D. and François, R. (2011). Rcpp: seamless R and C++++ integration. J. Stat. Software 40: 1–18. https://doi.org/10.18637/jss.v040.i08.Search in Google Scholar

Gough, B. (2009). GNU scientific library reference manual, 3rd ed. Godalming, Surrey, England: Network Theory Ltd.Search in Google Scholar

Guo, W., Sarkar, S.K., and Peddada, S.D. (2010). Controlling false discoveries in multidimensional directional decisions, with applications to gene expression data on ordered categories. Biometrics 66: 485–492. https://doi.org/10.1111/j.1541-0420.2009.01292.x.Search in Google Scholar PubMed PubMed Central

Hardcastle, T.J. and Kelly, K.A. (2013). Empirical Bayesian analysis of paired high-throughput sequencing data with a beta-binomial distribution. BMC Bioinf. 14: 135. https://doi.org/10.1186/1471-2105-14-135.Search in Google Scholar PubMed PubMed Central

Johnson, V.E. and Rossell, D. (2010). On the use of non-local prior densities in Bayesian hypothesis tests. J. Roy. Stat. Soc. B 72: 143–170. https://doi.org/10.1111/j.1467-9868.2009.00730.x.Search in Google Scholar

Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15: 1. https://doi.org/10.1186/s13059-014-0550-8.Search in Google Scholar PubMed PubMed Central

McCarthy, D.J., Chen, Y., and Smyth, G.K. (2012). Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Res. 40: 4288–4297, https://doi.org/10.1093/nar/gks042.Search in Google Scholar PubMed PubMed Central

Müller, P., Parmigiani, G., Robert, C., and Rousseau, J. (2004). Optimal sample size for multiple testing: the case of gene expression microarrays. J. Am. Stat. Assoc. 99: 990–1001. https://doi.org/10.1198/016214504000001646.Search in Google Scholar

Newton, M.A., Noueiry, A., Sarkar, D., and Ahlquist, P. (2004). Detecting differential gene expression with a semiparametric hierarchical mixture method. Biostatistics 5: 155–176. https://doi.org/10.1093/biostatistics/5.2.155.Search in Google Scholar PubMed

Qiu, J. and Cui, X. (2010). Evaluation of a statistical equivalence test applied to microarray data. J. Biopharm. Stat. 20: 240–266. https://doi.org/10.1080/10543400903572738.Search in Google Scholar PubMed

Robinson, M.D. and Oshlack, A. (2010). A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol. 11: 1. https://doi.org/10.1186/gb-2010-11-3-r25.Search in Google Scholar PubMed PubMed Central

Scott, J.G. and Berger, J.O. (2010). Bayes and empirical-Bayes multiplicity adjustment in the variable-selection problem. Ann. Stat. 38: 2587–2619, https://doi.org/10.1214/10-aos792.Search in Google Scholar

Tuke, J., Glonek, G., and Solomon, P. (2008). Gene profiling for determining pluripotent genes in a time course microarray experiment. Biostatistics 10: 80–93. https://doi.org/10.1093/biostatistics/kxn017.Search in Google Scholar PubMed

Valdés-López, O., Khan, S.M., Schmitz, R.J., Cui, S., Qiu, J., Joshi, T., Xu, D., Diers, B., Ecker, J.R., and Stacey, G. (2014). Genotypic variation of gene expression during the soybean innate immunity response. Plant Genet. Resour. 12: S27–S30. https://doi.org/10.1017/s1479262114000197.Search in Google Scholar


Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/sagmb-2022-0025).


Received: 2022-05-10
Accepted: 2023-02-13
Published Online: 2023-04-24

© 2023 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 7.5.2024 from https://www.degruyter.com/document/doi/10.1515/sagmb-2022-0025/html
Scroll to top button