IDBA-UD: a de novo assembler for single-cell and metagenomic sequencing data with highly uneven depth

• Published in: Bioinformatics (Oxford, England) Vol. 28; no. 11; pp. 1420 - 1428
• Main Authors: YU PENG, LEUNG, Henry C. M, YIU, S. M, CHIN, Francis Y. L
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.06.2012
• Subjects: Algorithms; Bacteria - genetics; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; General aspects; Genome; High-Throughput Nucleotide Sequencing; Mathematics in biology. Statistical analysis. Models. Metrology. Data processing in biology (general aspects); Metagenomics - methods; Sequence Analysis, DNA - methods; Single-Cell Analysis - methods; Isolated cell; Data; Sequencing; Metagenome; De novo
• ISSN: 1367-4803; 1367-4811
• DOI: 10.1093/bioinformatics/bts174

Next-generation sequencing allows us to sequence reads from a microbial environment using single-cell sequencing or metagenomic sequencing technologies. However, both technologies suffer from the problem that sequencing depth of different regions of a genome or genomes from different species are highly uneven. Most existing genome assemblers usually have an assumption that sequencing depths are even. These assemblers fail to construct correct long contigs. We introduce the IDBA-UD algorithm that is based on the de Bruijn graph approach for assembling reads from single-cell sequencing or metagenomic sequencing technologies with uneven sequencing depths. Several non-trivial techniques have been employed to tackle the problems. Instead of using a simple threshold, we use multiple depthrelative thresholds to remove erroneous k-mers in both low-depth and high-depth regions. The technique of local assembly with paired-end information is used to solve the branch problem of low-depth short repeat regions. To speed up the process, an error correction step is conducted to correct reads of high-depth regions that can be aligned to highconfident contigs. Comparison of the performances of IDBA-UD and existing assemblers (Velvet, Velvet-SC, SOAPdenovo and Meta-IDBA) for different datasets, shows that IDBA-UD can reconstruct longer contigs with higher accuracy. The IDBA-UD toolkit is available at our website http://www.cs.hku.hk/~alse/idba_ud