SPATA: A Seeding and Patching Algorithm for Hybrid Transcriptome Assembly

TL;DR

SPATA is a hybrid transcriptome assembly algorithm that combines local alignment and de novo assembly to improve accuracy without relying on splice-aware aligners, suitable for incomplete reference genomes.

Contribution

The paper introduces SPATA, a novel hybrid approach that localizes reads to genomic loci and performs targeted de novo assembly, addressing limitations of existing methods.

Findings

High accuracy and precision demonstrated in simulations

Effective for species with incomplete reference genomes

Open-source software available for use

Abstract

Transcriptome assembly from RNA-Seq reads is an active area of bioinformatics research. The ever-declining cost and the increasing depth of RNA-Seq have provided unprecedented opportunities to better identify expressed transcripts. However, the nonlinear transcript structures and the ultra-high throughput of RNA-Seq reads pose significant algorithmic and computational challenges to the existing transcriptome assembly approaches, either reference-guided or de novo. While reference-guided approaches offer good sensitivity, they rely on alignment results of the splice-aware aligners and are thus unsuitable for species with incomplete reference genomes. In contrast, de novo approaches do not depend on the reference genome but face a computational daunting task derived from the complexity of the graph built for the whole transcriptome. In response to these challenges, we present a hybrid approach to exploit an incomplete reference genome without relying on splice-aware aligners. We have designed a split-and-align procedure to efficiently localize the reads to individual genomic loci, which is followed by an accurate de novo assembly to assemble reads falling into each locus. Using extensive simulation data, we demonstrate a high accuracy and precision in transcriptome reconstruction by comparing to selected transcriptome assembly tools. Our method is implemented in assemblySAM, a GUI software freely available at http://sammate.sourceforge.net.