Paired-end RNA-Seq provides more accurate isoform abundance estimates than single end sequencing

Recently, ultra high-throughput sequencing of RNA (RNA-Seq) has been developed as an approach for analysis of gene expression. By obtaining tens or even hundreds of millions of reads of transcribed sequences, an RNA-Seq experiment can offer a comprehensive survey of the population of genes (transcripts) in any sample of interest.

The authors introduce a statistical model for estimating isoform abundance from RNA-Seq data and is flexible enough to accommodate both single end and paired end RNA-Seq data and sampling bias along the length of the transcript. Based on the derivation of minimal sufficient statistics for the model, a computationally feasible implementation of the maximum likelihood estimator of the model is provided.

Further, it is shown that using paired end RNA-Seq provides more accurate isoform abundance estimates than single end sequencing at fixed sequencing depth. Simulation studies are also given.

Salzman J, Jiang H, Wong WH. (2001) Statistical Modeling of RNA-Seq Data. Statist Sci 26(1), 62-83. [abstract]