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Open Access Highly Accessed Methodology article

NSMAP: A method for spliced isoforms identification and quantification from RNA-Seq

Zheng Xia13, Jianguo Wen23, Chung-Che Chang23 and Xiaobo Zhou13*

Author Affiliations

1 Department of Radiology, The Methodist Hospital Research Institute, Houston, TX 77030, USA

2 Department of Pathology, The Methodist Hospital Research Institute, Houston, TX 77030, USA

3 Weill Cornell Medical College, New York, NY 10065, USA

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BMC Bioinformatics 2011, 12:162  doi:10.1186/1471-2105-12-162

Published: 16 May 2011

Abstract

Background

The development of techniques for sequencing the messenger RNA (RNA-Seq) enables it to study the biological mechanisms such as alternative splicing and gene expression regulation more deeply and accurately. Most existing methods employ RNA-Seq to quantify the expression levels of already annotated isoforms from the reference genome. However, the current reference genome is very incomplete due to the complexity of the transcriptome which hiders the comprehensive investigation of transcriptome using RNA-Seq. Novel study on isoform inference and estimation purely from RNA-Seq without annotation information is desirable.

Results

A

    N
onnegativity and
    S
parsity constrained
    M
aximum
    A
    P
osteriori (NSMAP) model has been proposed to estimate the expression levels of isoforms from RNA-Seq data without the annotation information. In contrast to previous methods, NSMAP performs identification of the structures of expressed isoforms and estimation of the expression levels of those expressed isoforms simultaneously, which enables better identification of isoforms. In the simulations parameterized by two real RNA-Seq data sets, more than 77% expressed isoforms are correctly identified and quantified. Then, we apply NSMAP on two RNA-Seq data sets of myelodysplastic syndromes (MDS) samples and one normal sample in order to identify differentially expressed known and novel isoforms in MDS disease.

Conclusions

NSMAP provides a good strategy to identify and quantify novel isoforms without the knowledge of annotated reference genome which can further realize the potential of RNA-Seq technique in transcriptome analysis. NSMAP package is freely available at https://sites.google.com/site/nsmapforrnaseq. webcite