Title
RNA-Seq gene expression estimation with read mapping uncertainty.
Abstract
RNA-Seq is a promising new technology for accurately measuring gene expression levels. Expression estimation with RNA-Seq requires the mapping of relatively short sequencing reads to a reference genome or transcript set. Because reads are generally shorter than transcripts from which they are derived, a single read may map to multiple genes and isoforms, complicating expression analyses. Previous computational methods either discard reads that map to multiple locations or allocate them to genes heuristically.We present a generative statistical model and associated inference methods that handle read mapping uncertainty in a principled manner. Through simulations parameterized by real RNA-Seq data, we show that our method is more accurate than previous methods. Our improved accuracy is the result of handling read mapping uncertainty with a statistical model and the estimation of gene expression levels as the sum of isoform expression levels. Unlike previous methods, our method is capable of modeling non-uniform read distributions. Simulations with our method indicate that a read length of 20-25 bases is optimal for gene-level expression estimation from mouse and maize RNA-Seq data when sequencing throughput is fixed.
Year
DOI
Venue
2010
10.1093/bioinformatics/btp692
Bioinformatics
Keywords
Field
DocType
complicating expression analysis,maize rna-seq data,inference method,gene-level expression estimation,previous method,read length,expression estimation,gene expression level,rna-seq gene expression estimation,single read,isoform expression level,genome,gene expression profiling,statistical model,gene expression,algorithms,computational biology
Genome,Data mining,RNA-Seq,Computer science,Inference,Gene mapping,DNA sequencing,Statistical model,Bioinformatics,Reference genome,Gene expression profiling
Journal
Volume
Issue
ISSN
26
4
1367-4811
Citations 
PageRank 
References 
84
7.00
4
Authors
5
Name
Order
Citations
PageRank
Bo Li157845.93
Victor Ruotti212315.30
Ron M Stewart312110.18
James A Thomson414019.20
Colin N. Dewey538624.24