Dream: powerful differential expression analysis for repeated measures designs

被引:131
作者
Hoffman, Gabriel E. [1 ,2 ,3 ]
Roussos, Panos [1 ,2 ,3 ,4 ,5 ]
机构
[1] Icahn Sch Med Mt Sinai, Pamela Sklar Div Psychiat Genom, New York, NY 10029 USA
[2] Icahn Sch Med Mt Sinai, Icahn Inst Data Sci & Genom Technol, New York, NY 10029 USA
[3] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA
[4] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA
[5] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN 2 South, Bronx, NY 10468 USA
关键词
RNA-SEQ DATA; QUANTIFICATION; MODEL; METAANALYSIS; NETWORKS; RISK; LOCI;
D O I
10.1093/bioinformatics/btaa687
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
A 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.
引用
收藏
页码:192 / 201
页数:10
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