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

Abstract 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 propo...

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Autores principales:	Hsuan-Lin Her, Po-Ting Lin, Yu-Wei Wu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	PangenomeNet Pan-genome Escherichia coli Functional network Antimicrobial resistance Computer applications to medicine. Medical informatics R858-859.7 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d4ae534ec5b34fc5bc58e2fe2f04c0d7
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spelling	oai:doaj.org-article:d4ae534ec5b34fc5bc58e2fe2f04c0d72021-11-14T12:13:06ZPangenomeNet: a pan-genome-based network reveals functional modules on antimicrobial resistome for Escherichia coli strains10.1186/s12859-021-04459-z1471-2105https://doaj.org/article/d4ae534ec5b34fc5bc58e2fe2f04c0d72021-11-01T00:00:00Zhttps://doi.org/10.1186/s12859-021-04459-zhttps://doaj.org/toc/1471-2105Abstract 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.Hsuan-Lin HerPo-Ting LinYu-Wei WuBMCarticlePangenomeNetPan-genomeEscherichia coliFunctional networkAntimicrobial resistanceComputer applications to medicine. Medical informaticsR858-859.7Biology (General)QH301-705.5ENBMC Bioinformatics, Vol 22, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PangenomeNet Pan-genome Escherichia coli Functional network Antimicrobial resistance Computer applications to medicine. Medical informatics R858-859.7 Biology (General) QH301-705.5
spellingShingle	PangenomeNet Pan-genome Escherichia coli Functional network Antimicrobial resistance Computer applications to medicine. Medical informatics R858-859.7 Biology (General) QH301-705.5 Hsuan-Lin Her Po-Ting Lin Yu-Wei Wu PangenomeNet: a pan-genome-based network reveals functional modules on antimicrobial resistome for Escherichia coli strains
description	Abstract 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.
format	article
author	Hsuan-Lin Her Po-Ting Lin Yu-Wei Wu
author_facet	Hsuan-Lin Her Po-Ting Lin Yu-Wei Wu
author_sort	Hsuan-Lin Her
title	PangenomeNet: a pan-genome-based network reveals functional modules on antimicrobial resistome for Escherichia coli strains
title_short	PangenomeNet: a pan-genome-based network reveals functional modules on antimicrobial resistome for Escherichia coli strains
title_full	PangenomeNet: a pan-genome-based network reveals functional modules on antimicrobial resistome for Escherichia coli strains
title_fullStr	PangenomeNet: a pan-genome-based network reveals functional modules on antimicrobial resistome for Escherichia coli strains
title_full_unstemmed	PangenomeNet: a pan-genome-based network reveals functional modules on antimicrobial resistome for Escherichia coli strains
title_sort	pangenomenet: a pan-genome-based network reveals functional modules on antimicrobial resistome for escherichia coli strains
publisher	BMC
publishDate	2021
url	https://doaj.org/article/d4ae534ec5b34fc5bc58e2fe2f04c0d7
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PangenomeNet: a pan-genome-based network reveals functional modules on antimicrobial resistome for Escherichia coli strains

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