TGS-GapCloser: A fast and accurate gap closer for large genomes with low coverage of error-prone long reads. Issue 9 (7th September 2020)

• Record Type: Journal Article
• Authors: Xu, Mengyang; Guo, Lidong; Gu, Shengqiang; Wang, Ou; Zhang, Rui; Peters, Brock A; Fan, Guangyi; Liu, Xin; Xu, Xun; Deng, Li; Zhang, Yongwei
• Is Part Of: GigaScience. Volume 9:Issue 9(2020)
• Publication Date: 2020-09-07
• Subjects: gap closure -- third-generation sequencing -- genome assembly -- ginkgo -- MHC; Information storage and retrieval systems -- Research -- Periodicals; Biology -- Research -- Periodicals; Medical sciences -- Research -- Periodicals; Database management -- Periodicals; 570.285
• DOI: 10.1093/gigascience/giaa094
• Languages: English
• ISSNs: 2047-217X

Abstract

Abstract: Background: Analyses that use genome assemblies are critically affected by the contiguity, completeness, and accuracy of those assemblies. In recent years single-molecule sequencing techniques generating long-read information have become available and enabled substantial improvement in contig length and genome completeness, especially for large genomes (>100 Mb), although bioinformatic tools for these applications are still limited. Findings: We developed a software tool to close sequence gaps in genome assemblies, TGS-GapCloser, that uses low-depth (∼10×) long single-molecule reads. The algorithm extracts reads that bridge gap regions between 2 contigs within a scaffold, error corrects only the candidate reads, and assigns the best sequence data to each gap. As a demonstration, we used TGS-GapCloser to improve the scaftig NG50 value of 3 human genome assemblies by 24-fold on average with only ∼10× coverage of Oxford Nanopore or Pacific Biosciences reads, covering with sequence data up to 94.8% gaps with 97.7% positive predictive value. These improved assemblies achieve 99.998% (Q46) single-base accuracy with final inserted sequences having 99.97% (Q35) accuracy, despite the high raw error rate of single-molecule reads, enabling high-quality downstream analyses, including up to a 31-fold increase in the scaftig NGA50 and up to 13.1% more complete BUSCO genes. Additionally, we show that even in ultra-large genome assemblies, such as the ginkgo (∼12 Gb), TGS-GapCloser can cover 71.6% of gaps with sequence data. Conclusions: TGS-GapCloser can close gaps in large genome assemblies using raw long reads quickly and cost-effectively. The final assemblies generated by TGS-GapCloser have improved contiguity and completeness while maintaining high accuracy. The software is available at https://github.com/BGI-Qingdao/TGS-GapCloser .