Motivation: RNA sequencing is now widely performed to study differential expression among experimental conditions. As tests are performed on a large number of genes, stringent false-discovery rate control is required at the expense of detection power. Ad hoc filtering techniques are regularly used to moderate this correction by removing genes with low signal, with little attention paid to their impact on downstream analyses.Results: We propose a data-driven method based on the Jaccard similarity index to calculate a filtering threshold for replicated RNA sequencing data. In comparisons with alternative data filters regularly used in practice, we demonstrate the effectiveness of our proposed method to correctly filter lowly expressed genes, leading to increased detection power for moderately to highly expressed genes. Interestingly, this data-driven threshold varies among experiments, highlighting the interest of the method proposed here.Availability: The proposed filtering method is implemented in the package available on Bioconductor.Contact:
andrea.rau@jouy.inra.frSupplementary information:
Supplementary data are available at Bioinformatics online.
Abstract. Gaussian graphical models are widely utilized to infer and visualize networks of dependencies between continuous variables. However, inferring the graph is difficult when the sample size is small compared to the number of variables. To reduce the number of parameters to estimate in the model, we propose a non-asymptotic model selection procedure supported by strong theoretical guarantees based on an oracle type inequality and a minimax lower bound. The covariance matrix of the model is approximated by a block-diagonal matrix. The structure of this matrix is detected by thresholding the sample covariance matrix, where the threshold is selected using the slope heuristic. Based on the block-diagonal structure of the covariance matrix, the estimation problem is divided into several independent problems: subsequently, the network of dependencies between variables is inferred using the graphical lasso algorithm in each block. The performance of the procedure is illustrated on simulated data. An application to a real gene expression dataset with a limited sample size is also presented: the dimension reduction allows attention to be objectively focused on interactions among smaller subsets of genes, leading to a more parsimonious and interpretable modular network.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.