Title | ||
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Benchmarking association analyses of continuous exposures with RNA-seq in observational studies |
Abstract | ||
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Large datasets of hundreds to thousands of individuals measuring RNA-seq in observational studies are becoming available. Many popular software packages for analysis of RNA-seq data were constructed to study differences in expression signatures in an experimental design with well-defined conditions (exposures). In contrast, observational studies may have varying levels of confounding transcript-exposure associations; further, exposure measures may vary from discrete (exposed, yes/no) to continuous (levels of exposure), with non-normal distributions of exposure. We compare popular software for gene expression-DESeq2, edgeR and limma-as well as linear regression-based analyses for studying the association of continuous exposures with RNA-seq. We developed a computation pipeline that includes transformation, filtering and generation of empirical null distribution of association P-values, and we apply the pipeline to compute empirical P-values with multiple testing correction. We employ a resampling approach that allows for assessment of false positive detection across methods, power comparison and the computation of quantile empirical P-values. The results suggest that linear regression methods are substantially faster with better control of false detections than other methods, even with the resampling method to compute empirical P-values. We provide the proposed pipeline with fast algorithms in an R package Olivia, and implemented it to study the associations of measures of sleep disordered breathing with RNA-seq in peripheral blood mononuclear cells in participants from the Multi-Ethnic Study of Atherosclerosis. |
Year | DOI | Venue |
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2021 | 10.1093/bib/bbab194 | BRIEFINGS IN BIOINFORMATICS |
Keywords | DocType | Volume |
observational studies, continuous exposure, non-normality, RNA-seq, empirical P-values | Journal | 22 |
Issue | ISSN | Citations |
6 | 1467-5463 | 0 |
PageRank | References | Authors |
0.34 | 0 | 13 |
Name | Order | Citations | PageRank |
---|---|---|---|
Tamar Sofer | 1 | 7 | 1.79 |
Nuzulul Kurniansyah | 2 | 0 | 0.34 |
François Aguet | 3 | 0 | 0.34 |
Kristin Ardlie | 4 | 0 | 0.34 |
Peter Durda | 5 | 0 | 0.34 |
Deborah A Nickerson | 6 | 14 | 2.83 |
Joshua D Smith | 7 | 0 | 0.34 |
Yongmei Liu | 8 | 0 | 0.34 |
Sina A Gharib | 9 | 4 | 0.83 |
Susan Redline | 10 | 0 | 0.34 |
Stephen S Rich | 11 | 20 | 3.44 |
Jerome I. Rotter | 12 | 1 | 1.05 |
Kent D. Taylor | 13 | 1 | 0.71 |