Typhi Mykrobe: fast and accurate lineage identification and antimicrobial resistance genotyping directly from sequence reads for the typhoid fever agent Salmonella Typhi

作者：Danielle J. Ingle, Jane Hawkey, Martin Hunt, Zamin Iqbal, Jacqueline A. Keane, Ayorinde O. Afolayan, Niyaz Ahmed, Saadia Andleeb, Philip Ashton, Isaac I. Bogoch, Megan E. Carey, Marie Anne Chattaway, John A. Crump, Paula Díaz, Benjamin P. Howden, Hidemasa Izumiya, Jobin John Jacob, Louise M. Judd, Arti Kapil, Karen H. Keddy, Justin Y. Kim, Myron M. Levine, Masatomo Morita, Satheesh Nair, Sophie Octavia, Iruka N. Okeke, Precious E. Osadebamwen, Sadia Rahman, Assaf Rokney, David A. Rasko, Varun Shamanna, Michael J. Sikorski, Anthony M. Smith, Gabriel Temitope Sunmonu, Kaitlin A. Tagg, Ryan R. Wick, Zoe A. Dyson, Kathryn E. Holt · 发表于：Genome Medicine · 年份：2025 · DOI：10.1186/s13073-025-01551-4 · 被引用次数：4 · 研究领域：Salmonella and Campylobacter epidemiology、Aquaculture disease management and microbiota、Bacterial Genetics and Biotechnology

BACKGROUND: Typhoid fever results from systemic infection with Salmonella enterica serovar Typhi (Typhi) and causes 10 million illnesses annually. Disease control relies on prevention (water, sanitation, and hygiene interventions or vaccination) and effective antimicrobial treatment. Antimicrobial-resistant (AMR) Typhi lineages have emerged and become established in many parts of the world. Knowledge of local pathogen populations informed by genomic surveillance, including of lineages (defined by the GenoTyphi scheme) and AMR determinants, is increasingly used to inform local treatment guidelines and to inform vaccination strategy. Current tools for genotyping Typhi require multiple read alignment or assembly steps and have not been validated for analysis of data generated with Oxford Nanopore Technologies (ONT) long-read sequencing devices. Here, we introduce Typhi Mykrobe, a command line software tool for rapid genotyping of Typhi lineages, AMR determinants, and plasmid replicons direct from sequencing reads. RESULTS: We validated Typhi Mykrobe lineage genotyping by comparison with the current standard read mapping-based approach and demonstrated 99.8% concordance across nearly 13,000 genomes sequenced with Illumina platforms. For the few isolates with discordant calls, we show that Typhi Mykrobe results are better supported by the evidence from raw sequence read data than the results generated using the mapping-based approach. We also demonstrate 99.9% concordance for dete...