Exploring high-quality microbial genomes by assembling short-reads with long-range connectivity

Zhenmiao Zhang, Jin Xiao, Hongbo Wang, Chao Yang, Yufen Huang, Zhen Yue, Yang Chen, Lijuan Han, Kejing Yin, Aiping Lyu, Xiaodong Fang and Lu Zhang ()
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Zhenmiao Zhang: Hong Kong Baptist University
Jin Xiao: Hong Kong Baptist University
Hongbo Wang: Hong Kong Baptist University
Chao Yang: Hong Kong Baptist University
Yufen Huang: BGI Research
Zhen Yue: BGI Research
Yang Chen: The Second Affiliated Hospital of Guangzhou University of Chinese
Lijuan Han: Kangmeihuada GeneTech Co., Ltd (KMHD)
Kejing Yin: Hong Kong Baptist University
Aiping Lyu: Hong Kong Baptist University
Xiaodong Fang: BGI Research
Lu Zhang: Hong Kong Baptist University

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Although long-read sequencing enables the generation of complete genomes for unculturable microbes, its high cost limits the widespread adoption of long-read sequencing in large-scale metagenomic studies. An alternative method is to assemble short-reads with long-range connectivity, which can be a cost-effective way to generate high-quality microbial genomes. Here, we develop Pangaea, a bioinformatic approach designed to enhance metagenome assembly using short-reads with long-range connectivity. Pangaea leverages connectivity derived from physical barcodes of linked-reads or virtual barcodes by aligning short-reads to long-reads. Pangaea utilizes a deep learning-based read binning algorithm to assemble co-barcoded reads exhibiting similar sequence contexts and abundances, thereby improving the assembly of high- and medium-abundance microbial genomes. Pangaea also leverages a multi-thresholding algorithm strategy to refine assembly for low-abundance microbes. We benchmark Pangaea on linked-reads and a combination of short- and long-reads from simulation data, mock communities and human gut metagenomes. Pangaea achieves significantly higher contig continuity as well as more near-complete metagenome-assembled genomes (NCMAGs) than the existing assemblers. Pangaea also generates three complete and circular NCMAGs on the human gut microbiomes.

Date: 2024
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DOI: 10.1038/s41467-024-49060-z

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