Dataset Information

StrainGE: a toolkit to track and characterize low-abundance strains in complex microbial communities.

ABSTRACT: Human-associated microbial communities comprise not only complex mixtures of bacterial species, but also mixtures of conspecific strains, the implications of which are mostly unknown since strain level dynamics are underexplored due to the difficulties of studying them. We introduce the Strain Genome Explorer (StrainGE) toolkit, which deconvolves strain mixtures and characterizes component strains at the nucleotide level from short-read metagenomic sequencing with higher sensitivity and resolution than other tools. StrainGE is able to identify strains at 0.1x coverage and detect variants for multiple conspecific strains within a sample from coverages as low as 0.5x.

SUBMITTER: van Dijk LR

PROVIDER: S-EPMC8900328 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

StrainGE: a toolkit to track and characterize low-abundance strains in complex microbial communities.

van Dijk Lucas R LR Walker Bruce J BJ Straub Timothy J TJ Worby Colin J CJ Grote Alexandra A Schreiber Henry L HL Anyansi Christine C Pickering Amy J AJ Hultgren Scott J SJ Manson Abigail L AL Abeel Thomas T Earl Ashlee M AM

Genome biology 20220307 1

Human-associated microbial communities comprise not only complex mixtures of bacterial species, but also mixtures of conspecific strains, the implications of which are mostly unknown since strain level dynamics are underexplored due to the difficulties of studying them. We introduce the Strain Genome Explorer (StrainGE) toolkit, which deconvolves strain mixtures and characterizes component strains at the nucleotide level from short-read metagenomic sequencing with higher sensitivity and resoluti ...[more]

PMID: 35255937

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Project description:BackgroundThe relationships between infections in early life and asthma are not completely understood. Likewise, the clinical relevance of microbial communities present in the respiratory tract is only partially known. A number of microbiome studies analyzing respiratory tract samples have found increased proportions of gamma-Proteobacteria including Haemophilus influenzae, Moraxella catarrhalis, and Firmicutes such as Streptococcus pneumoniae. The aim of this study was to present a new approach that combines RNA microbial identification with host gene expression to characterize and validate metagenomic taxonomic profiling in individuals with asthma.MethodsUsing whole metagenomic shotgun RNA sequencing, we characterized and compared the microbial communities of individuals, children and adolescents, with asthma and controls. The resulting data were analyzed by partitioning human and microbial reads. Microbial reads were then used to characterize the microbial diversity of each patient, and potential differences between asthmatic and healthy groups. Human reads were used to assess the expression of known genes involved in the host immune response to specific pathogens and detect potential differences between those with asthma and controls.ResultsMicrobial communities in the nasal cavities of children differed significantly between asthmatics and controls. After read count normalization, some bacterial species were significantly overrepresented in asthma patients (Wald test, p-value < 0.05), including Escherichia coli and Psychrobacter. Among these, Moraxella catarrhalis exhibited ~14-fold over abundance in asthmatics versus controls. Differential host gene expression analysis confirms that the presence of Moraxella catarrhalis is associated to a specific M. catarrhalis core gene signature expressed by the host.ConclusionsFor the first time, we show the power of combining RNA taxonomic profiling and host gene expression signatures for microbial identification. Our approach not only identifies microbes from metagenomic data, but also adds support to these inferences by determining if the host is mounting a response against specific infectious agents. In particular, we show that M. catarrhalis is abundant in asthma patients but not in controls, and that its presence is associated with a specific host gene expression signature.

Project description:Constraint-based modeling has risen as an alternative for characterizing metabolism of communities. Adaptations of flux balance analysis have been proposed to model metabolic interactions, which in most cases consider the maximization of biomass production as their objective. In nature, novel essential functions are not directly related to cell growth force communities to display suboptimal growth rates. These suboptimal states allow a degree of plasticity in their metabolism, thus allowing quick shifts between alternative flux distributions as an initial response to environmental changes. In this work, we introduce the abundance-growth space as a representation of metabolic phenotypes of a community. This space is defined by the composition of a community, represented by its members' relative abundances, and their growth rate. The analysis of this space allows us to pinpoint how critical reactions respond to shifts of the environment, showing where changes in community plasticity occur. Interestingly, it highlights the relevance of the relative abundance of its members in the lost or gain of plasticity. This method is applied to two simple communities that exchange metabolites. A synthetic community of two mutant Escherichia coli strains and an environmental bioleaching community composed by Acidithiobacillus ferrooxidans Wenelen and Sulfobacillus thermosulfidooxidans Cutipay, where only Cutipay consumes organic matter disposed of by the community.IMPORTANCEIn nature, organisms live in communities and not as isolated species, and their interactions provide a source of resilience to environmental disturbances. Despite their importance in ecology, human health, and industry, understanding how organisms interact in different environments remains an open question.In this work, we provide a novel approach that, only using genomic information, studies the metabolic phenotype exhibited by communities, where the exploration of suboptimal growth flux distributions and the composition of a community allows to unveil its capacity to respond to environmental changes, shedding light of the degrees of metabolic plasticity inherent to the community.

Dataset Information

StrainGE: a toolkit to track and characterize low-abundance strains in complex microbial communities.

Publications

StrainGE: a toolkit to track and characterize low-abundance strains in complex microbial communities.

Similar Datasets

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