Mengyin Lu1, Matthew Stephens1,2. 1. Department of Statistics, University of Chicago, Chicago, 60637, USA. 2. Department of Human Genetics, University of Chicago, Chicago, 60637, USA.
Abstract
MOTIVATION: Genomic studies often involve estimation of variances of thousands of genes (or other genomic units) from just a few measurements on each. For example, variance estimation is an important step in gene expression analyses aimed at identifying differentially expressed genes. A common approach to this problem is to use an Empirical Bayes (EB) method that assumes the variances among genes follow an inverse-gamma distribution. This distributional assumption is relatively inflexible; for example, it may not capture 'outlying' genes whose variances are considerably bigger than usual. Here we describe a more flexible EB method, capable of capturing a much wider range of distributions. Indeed, the main assumption is that the distribution of the variances is unimodal (or, as an alternative, that the distribution of the precisions is unimodal). We argue that the unimodal assumption provides an attractive compromise between flexibility, computational tractability and statistical efficiency. RESULTS: We show that this more flexible approach provides competitive performance with existing methods when the variances truly come from an inverse-gamma distribution, and can outperform them when the distribution of the variances is more complex. In analyses of several human gene expression datasets from the Genotype Tissues Expression consortium, we find that our more flexible model often fits the data appreciably better than the single inverse gamma distribution. At the same time we find that in these data this improved model fit leads to only small improvements in variance estimates and detection of differentially expressed genes. AVAILABILITY AND IMPLEMENTATION: Our methods are implemented in an R package vashr available from http://github.com/mengyin/vashr CONTACT: mstephens@uchicago.eduSupplementary information: Supplementary data are available at Bioinformatics online.
MOTIVATION: Genomic studies often involve estimation of variances of thousands of genes (or other genomic units) from just a few measurements on each. For example, variance estimation is an important step in gene expression analyses aimed at identifying differentially expressed genes. A common approach to this problem is to use an Empirical Bayes (EB) method that assumes the variances among genes follow an inverse-gamma distribution. This distributional assumption is relatively inflexible; for example, it may not capture 'outlying' genes whose variances are considerably bigger than usual. Here we describe a more flexible EB method, capable of capturing a much wider range of distributions. Indeed, the main assumption is that the distribution of the variances is unimodal (or, as an alternative, that the distribution of the precisions is unimodal). We argue that the unimodal assumption provides an attractive compromise between flexibility, computational tractability and statistical efficiency. RESULTS: We show that this more flexible approach provides competitive performance with existing methods when the variances truly come from an inverse-gamma distribution, and can outperform them when the distribution of the variances is more complex. In analyses of several human gene expression datasets from the Genotype Tissues Expression consortium, we find that our more flexible model often fits the data appreciably better than the single inverse gamma distribution. At the same time we find that in these data this improved model fit leads to only small improvements in variance estimates and detection of differentially expressed genes. AVAILABILITY AND IMPLEMENTATION: Our methods are implemented in an R package vashr available from http://github.com/mengyin/vashr CONTACT: mstephens@uchicago.eduSupplementary information: Supplementary data are available at Bioinformatics online.