ResMiCo: Increasing the quality of metagenome-assembled genomes with deep learning

PLoS Comput Biol. 2023 May 1;19(5):e1011001. doi: 10.1371/journal.pcbi.1011001. eCollection 2023 May.

Abstract

The number of published metagenome assemblies is rapidly growing due to advances in sequencing technologies. However, sequencing errors, variable coverage, repetitive genomic regions, and other factors can produce misassemblies, which are challenging to detect for taxonomically novel genomic data. Assembly errors can affect all downstream analyses of the assemblies. Accuracy for the state of the art in reference-free misassembly prediction does not exceed an AUPRC of 0.57, and it is not clear how well these models generalize to real-world data. Here, we present the Residual neural network for Misassembled Contig identification (ResMiCo), a deep learning approach for reference-free identification of misassembled contigs. To develop ResMiCo, we first generated a training dataset of unprecedented size and complexity that can be used for further benchmarking and developments in the field. Through rigorous validation, we show that ResMiCo is substantially more accurate than the state of the art, and the model is robust to novel taxonomic diversity and varying assembly methods. ResMiCo estimated 7% misassembled contigs per metagenome across multiple real-world datasets. We demonstrate how ResMiCo can be used to optimize metagenome assembly hyperparameters to improve accuracy, instead of optimizing solely for contiguity. The accuracy, robustness, and ease-of-use of ResMiCo make the tool suitable for general quality control of metagenome assemblies and assembly methodology optimization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Deep Learning*
  • Genomics / methods
  • Metagenome* / genetics
  • Metagenomics
  • Sequence Analysis, DNA / methods
  • Software

Grants and funding

This work was supported by Eidgenössische Technische Hochschule Zürich core funding (OM, DD, and GR), the Max Planck Institute (NDY, REL, and BS), and the Eidgenössische Technische Hochschule Strategic Focus Area - Personalized Health and Related Technologies (project #106 to DD). OM was also supported by the Max Planck ETH Center for Learning Systems. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. OM, DD, and GR received a salary from the Eidgenössische Technische Hochschule Zürich; NDY, REL, and BS received a salary from the Max Planck Institute.