Dataset Information

DART: a fast and accurate RNA-seq mapper with a partitioning strategy.

ABSTRACT: MOTIVATION:In recent years, the massively parallel cDNA sequencing (RNA-Seq) technologies have become a powerful tool to provide high resolution measurement of expression and high sensitivity in detecting low abundance transcripts. However, RNA-seq data requires a huge amount of computational efforts. The very fundamental and critical step is to align each sequence fragment against the reference genome. Various de novo spliced RNA aligners have been developed in recent years. Though these aligners can handle spliced alignment and detect splice junctions, some challenges still remain to be solved. With the advances in sequencing technologies and the ongoing collection of sequencing data in the ENCODE project, more efficient alignment algorithms are highly demanded. Most read mappers follow the conventional seed-and-extend strategy to deal with inexact matches for sequence alignment. However, the extension is much more time consuming than the seeding step. RESULTS:We proposed a novel RNA-seq de novo mapping algorithm, call DART, which adopts a partitioning strategy to avoid the extension step. The experiment results on synthetic datasets and real NGS datasets showed that DART is a highly efficient aligner that yields the highest or comparable sensitivity and accuracy compared to most state-of-the-art aligners, and more importantly, it spends the least amount of time among the selected aligners. AVAILABILITY AND IMPLEMENTATION:https://github.com/hsinnan75/DART. SUPPLEMENTARY INFORMATION:Supplementary data are available at Bioinformatics online.

SUBMITTER: Lin HN

PROVIDER: S-EPMC5860201 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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DART: a fast and accurate RNA-seq mapper with a partitioning strategy.

Lin Hsin-Nan HN Hsu Wen-Lian WL

Bioinformatics (Oxford, England) 20180101 2

<h4>Motivation</h4>In recent years, the massively parallel cDNA sequencing (RNA-Seq) technologies have become a powerful tool to provide high resolution measurement of expression and high sensitivity in detecting low abundance transcripts. However, RNA-seq data requires a huge amount of computational efforts. The very fundamental and critical step is to align each sequence fragment against the reference genome. Various de novo spliced RNA aligners have been developed in recent years. Though thes ...[more]

PMID: 28968831

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Project description:RNA-sequencing (RNA-seq) provides a comprehensive quantification of transcriptomic activities in biological samples. Formalin-Fixed Paraffin-Embedded (FFPE) samples are collected as part of routine clinical procedure, and are the most widely available biological sample format in medical research and patient care. Normalization is an essential step in RNA-seq data analysis. A number of normalization methods, though developed for RNA-seq data from fresh frozen (FF) samples, can be used with FFPE samples as well. The only extant normalization method specifically designed for FFPE RNA-seq data, MIXnorm, which has been shown to outperform the normalization methods, but at the cost of a complex mixture model and a high computational burden. It is therefore important to adapt MIXnorm for simplicity and computational efficiency while maintaining superior performance. Furthermore, it is critical to develop an integrated tool that performs commonly used normalization methods for both FF and FFPE RNA-seq data. We developed a new normalization method for FFPE RNA-seq data, named SMIXnorm, based on a simplified two-component mixture model compared to MIXnorm to facilitate computation. The expression levels of expressed genes are modeled by normal distributions without truncation, and those of non-expressed genes are modeled by zero-inflated Poisson distributions. The maximum likelihood estimates of the model parameters are obtained by a nested Expectation-Maximization algorithm with a less complicated latent variable structure, and closed-form updates are available within each iteration. Real data applications and simulation studies show that SMIXnorm greatly reduces computing time compared to MIXnorm, without sacrificing the performance. More importantly, we developed a web-based tool, RNA-seq Normalization (RSeqNorm), that offers a simple workflow to compute normalized RNA-seq data for both FFPE and FF samples. It includes SMIXnorm and MIXnorm for FFPE RNA-seq data, together with five commonly used normalization methods for FF RNA-seq data. Users can easily upload a raw RNA-seq count matrix and select one of the seven normalization methods to produce a downloadable normalized expression matrix for any downstream analysis. The R package is available at https://github.com/S-YIN/RSEQNORM. The web-based tool, RSeqNorm is available at http://lce.biohpc.swmed.edu/rseqnorm with no restriction to use or redistribute.

Dataset Information

DART: a fast and accurate RNA-seq mapper with a partitioning strategy.

Publications

DART: a fast and accurate RNA-seq mapper with a partitioning strategy.

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