Title
Accurate inference of isoforms from multiple sample RNA-Seq data.
Abstract
RNA-Seq based transcriptome assembly has become a fundamental technique for studying expressed mRNAs (i.e., transcripts or isoforms) in a cell using high-throughput sequencing technologies, and is serving as a basis to analyze the structural and quantitative differences of expressed isoforms between samples. However, the current transcriptome assembly algorithms are not specifically designed to handle large amounts of errors that are inherent in real RNA-Seq datasets, especially those involving multiple samples, making downstream differential analysis applications difficult. On the other hand, multiple sample RNA-Seq datasets may provide more information than single sample datasets that can be utilized to improve the performance of transcriptome assembly and abundance estimation, but such information remains overlooked by the existing assembly tools.We formulate a computational framework of transcriptome assembly that is capable of handling noisy RNA-Seq reads and multiple sample RNA-Seq datasets efficiently. We show that finding an optimal solution under this framework is an NP-hard problem. Instead, we develop an efficient heuristic algorithm, called Iterative Shortest Path (ISP), based on linear programming (LP) and integer linear programming (ILP). Our preliminary experimental results on both simulated and real datasets and comparison with the existing assembly tools demonstrate that (i) the ISP algorithm is able to assemble transcriptomes with a greatly increased precision while keeping the same level of sensitivity, especially when many samples are involved, and (ii) its assembly results help improve downstream differential analysis. The source code of ISP is freely available at http://alumni.cs.ucr.edu/~liw/isp.html.
Year
DOI
Venue
2015
10.1186/1471-2164-16-S2-S15
BMC Genomics
Keywords
Field
DocType
Integer Linear Programming, Transcriptome Assembly, Differential Analysis, Assembly Result, Integer Linear Programming Problem
RNA-Seq,Biology,Shortest path problem,Source code,Heuristic (computer science),Inference,Integer programming,Software,Linear programming,Bioinformatics,Genetics
Journal
Volume
Issue
ISSN
16 Suppl 2
S-2
1471-2164
Citations 
PageRank 
References 
4
0.71
10
Authors
5
Name
Order
Citations
PageRank
Masruba Tasnim140.71
Shining Ma240.71
Ei-Wen Yang3101.84
Tao Jiang41809155.32
Wei Li5504.38