PangenomeNet: a pan-genome-based network reveals functional modules on antimicrobial resistome for Escherichia coli strains

Hsuan Lin Her, Po Ting Lin, Yu Wei Wu

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摘要

Background: Discerning genes crucial to antimicrobial resistance (AMR) mechanisms is becoming more and more important to accurately and swiftly identify AMR pathogenic strains. Pangenome-wide association studies (e.g. Scoary) identified numerous putative AMR genes. However, only a tiny proportion of the putative resistance genes are annotated by AMR databases or Gene Ontology. In addition, many putative resistance genes are of unknown function (termed hypothetical proteins). An annotation tool is crucially needed in order to reveal the functional organization of the resistome and expand our knowledge of the AMR gene repertoire. Results: We developed an approach (PangenomeNet) for building co-functional networks from pan-genomes to infer functions for hypothetical genes. Using Escherichia coli as an example, we demonstrated that it is possible to build co-functional network from its pan-genome using co-inheritance, domain-sharing, and protein–protein-interaction information. The investigation of the network revealed that it fits the characteristics of biological networks and can be used for functional inferences. The subgraph consisting of putative meropenem resistance genes consists of clusters of stress response genes and resistance gene acquisition pathways. Resistome subgraphs also demonstrate drug-specific AMR genes such as beta-lactamase, as well as functional roles shared among multiple classes of drugs, mostly in the stress-related pathways. Conclusions: By demonstrating the idea of pan-genome-based co-functional network on the E. coli species, we showed that the network can infer functional roles of the genes, including those without functional annotations, and provides holistic views on the putative antimicrobial resistomes. We hope that the pan-genome network idea can help formulate hypothesis for targeted experimental works.

原文英語
文章編號548
期刊BMC Bioinformatics
22
發行號1
DOIs
出版狀態已發佈 - 12月 2021

ASJC Scopus subject areas

  • 結構生物學
  • 生物化學
  • 分子生物學
  • 電腦科學應用
  • 應用數學

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