Target-enriched long-read sequencing (TELSeq) contextualizes antimicrobial resistance genes in metagenomes Ilya B. Slizovskiy, Marco Oliva, Jonathen K. Settle, Lidiya V. Zyskina, Mattia Prosperi, Christina Boucher & Noelle R. Noyes. Microbiome | volume 10 | Article number: 185 | 2022 

Current metagenomic sequencing methods (e.g. Illumina, PacBio, Oxford Nanopore) produce data that suffer from low sensitivity and an inability to accurately reconstruct partial or full genomes, particularly those in low abundance. These limitations preclude colocalization analysis, i.e., characterizing the genomic context of genes and functions within a metagenomic sample. Genomic context is especially crucial for functions associated with horizontal gene transfer (HGT) via mobile genetic elements (MGEs), for example antimicrobial resistance (AMR). To overcome this current limitation of metagenomics, we present a method for comprehensive and accurate reconstruction of antimicrobial resistance genes (ARGs) and MGEs from metagenomic DNA, termed target-enriched long-read sequencing (TELSeq).

TELSeq achievs a much higher ARG recovery (>1,000-fold) and sensitivity than other methods across diverse metagenomes, revealing an extensive resistome profile comprising many low-abundance ARGs, including some with public health importance. TELSeq can provide a nuanced view of the genomic context of microbial resistomes and thus has wide-ranging applications in public, animal, and human health, as well as environmental surveillance and monitoring of AMR.