A powerful and flexible statistical framework for testing hypotheses of allele-specific gene expression from RNA-seq data
- 26 August 2011
- journal article
- Published by Cold Spring Harbor Laboratory in Genome Research
- Vol. 21 (10), 1728-1737
- https://doi.org/10.1101/gr.119784.110
Abstract
Variation in gene expression is thought to make a significant contribution to phenotypic diversity among individuals within populations. Although high-throughput cDNA sequencing offers a unique opportunity to delineate the genome-wide architecture of regulatory variation, new statistical methods need to be developed to capitalize on the wealth of information contained in RNA-seq data sets. To this end, we developed a powerful and flexible hierarchical Bayesian model that combines information across loci to allow both global and locus-specific inferences about allele-specific expression (ASE). We applied our methodology to a large RNA-seq data set obtained in a diploid hybrid of two diverse Saccharomyces cerevisiae strains, as well as to RNA-seq data from an individual human genome. Our statistical framework accurately quantifies levels of ASE with specified false-discovery rates, achieving high reproducibility between independent sequencing platforms. We pinpoint loci that show unusual and biologically interesting patterns of ASE, including allele-specific alternative splicing and transcription termination sites. Our methodology provides a rigorous, quantitative, and high-resolution tool for profiling ASE across whole genomes.Keywords
This publication has 41 references indexed in Scilit:
- BFAST: An Alignment Tool for Large Scale Genome ResequencingPLOS ONE, 2009
- Global patterns of cis variation in human cells revealed by high-density allelic expression analysisNature Genetics, 2009
- Inherited Variation in Gene ExpressionAnnual Review of Genomics and Human Genetics, 2009
- Digital RNA allelotyping reveals tissue-specific and allele-specific gene expression in humanNature Methods, 2009
- Global mapping of protein-DNA interactions in vivo by digital genomic footprintingNature Methods, 2009
- Allele-specific expression assays using SolexaBMC Genomics, 2009
- RNA-Seq: a revolutionary tool for transcriptomicsNature Reviews Genetics, 2009
- Substantial biases in ultra-short read data sets from high-throughput DNA sequencingNucleic Acids Research, 2008
- Differential Allelic Expression in the Human Genome: A Robust Approach To Identify Genetic and Epigenetic Cis-Acting Mechanisms Regulating Gene ExpressionPLoS Genetics, 2008
- Genetics of global gene expressionNature Reviews Genetics, 2006