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SUMMARY: Large-scale transcriptome studies with multiple samples per individual are widely used to study disease biology. Yet, current methods for differential expression are inadequate for cross-individual testing for these repeated measures designs. Most problematic, we observe across multiple datasets that current methods can give reproducible false-positive findings that are driven by genetic regulation of gene expression, yet are unrelated to the trait of interest. Here, we introduce a statistical software package, dream, that increases power, controls the false positive rate, enables multiple types of hypothesis tests, and integrates with standard workflows. In 12 analyses in 6 independent datasets, dream yields biological insight not found with existing software while addressing the issue of reproducible false-positive findings. AVAILABILITY AND IMPLEMENTATION: Dream is available within the variancePartition Bioconductor package at http://bioconductor.org/packages/variancePartition. CONTACT: gabriel.hoffman@mssm.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Hoffman et al. (Thu,) studied this question.