Transcriptome assembly and isoform expression level estimation from biased RNA-Seq reads.
BACKGROUND
RNA-Seq uses the high-throughput sequencing technology to identify and quantify transcriptome at an unprecedented high resolution and low cost. However, RNA-Seq reads are usually not uniformly distributed and biases in RNA-Seq data post great challenges in many applications including transcriptome assembly and the expression level estimation of genes or isoforms. Much effort has been made in the literature to calibrate the expression level estimation from biased RNA-Seq data, but the effect of biases on transcriptome assembly remains largely unexplored.


RESULTS
Here, we propose a statistical framework for both transcriptome assembly and isoform expression level estimation from biased RNA-Seq data. Using a quasi-multinomial distribution model, our method is able to capture various types of RNA-Seq biases, including positional, sequencing and mappability biases. Our experimental results on simulated and real RNA-Seq datasets exhibit interesting effects of RNA-Seq biases on both transcriptome assembly and isoform expression level estimation. The advantage of our method is clearly shown in the experimental analysis by its high sensitivity and precision in transcriptome assembly and the high concordance of its estimated expression levels with quantitative reverse transcription-polymerase chain reaction data.


BACKGROUND
CEM is freely available at http://www.cs.ucr.edu/~liw/cem.html.


BACKGROUND
liw@cs.ucr.edu.


BACKGROUND
Supplementary data are available at Bioinformatics online.
Department of Computer Science and Engineering, University of California, Riverside, Riverside CA 92507, USA. liw@cs.ucr.edu
Wei
W
Li
Tao
T
Jiang
D000465:Algorithms; D020869:Gene Expression Profiling / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics; D017423:Sequence Analysis, RNA / Q000379:methods*; D014158:Transcription, Genetic
D020033:Protein Isoforms