Accurate and robust inference of microbial growth dynamics from metagenomic sequencing

AbstractPatterns of sequencing coverage along a bacterial genome—summarized by a peak-to-trough ratio (PTR)—have been shown to accurately reflect microbial growth rates, revealing a new facet of microbial dynamics and host-microbe interactions. Here, we introduce CoPTR (Compute PTR): a tool for computing PTRs from complete reference genomes and assemblies. We show that CoPTR is more accurate than the current state-of-the-art, while also providing more PTR estimates overall. We further develop theory formalizing a biological interpretation for PTRs. Using a reference database of 2935 species, we applied CoPTR to a case-control study of 1304 metagenomic samples from 106 individuals with irritable bowel disease. We show that PTRs have high inter-individual variation, are only loosely correlated with relative abundances, and are associated with disease status. We conclude by demonstrating how PTRs can be combined with relative abundances and metabolomics to investigate their effect on the microbiome.AvailabilityCoPTR is available from https://github.com/tyjo/coptr, with documentation on https://coptr.readthedocs.io.

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Accurate and robust inference of microbial growth dynamics from metagenomic sequencing reveals personalized growth rates

Genome Research ◽

10.1101/gr.275533.121 ◽

2022 ◽

pp. gr.275533.121

Author(s):

Tyler A Joseph ◽

Philippe Chlenski ◽

Aviya Litman ◽

Tal Korem ◽

Itsik Pe'er

Keyword(s):

Growth Rates ◽

Microbial Growth ◽

Bacterial Genome ◽

Growth Dynamics ◽

Disease Status ◽

Reference Database ◽

Metagenomic Sequencing ◽

Biological Interpretation ◽

Relative Abundances ◽

Host Microbe Interactions

Patterns of sequencing coverage along a bacterial genome---summarized by a peak-to-trough ratio (PTR)---have been shown to accurately reflect microbial growth rates, revealing a new facet of microbial dynamics and host-microbe interactions. Here, we introduce CoPTR (Compute PTR): a tool for computing PTRs from complete reference genomes and assemblies. Using simulations and data from growth experiments in simple and complex communities, we show that CoPTR is more accurate than the current state-of-the-art, while also providing more PTR estimates overall. We further develop theory formalizing a biological interpretation for PTRs. Using a reference database of 2935 species, we applied CoPTR to a case-control study of 1304 metagenomic samples from 106 individuals with inflammatory bowel disease. We show that growth rates are personalized, are only loosely correlated with relative abundances, and are associated with disease status. We conclude by demonstrating how PTRs can be combined with relative abundances and metabolomics to investigate their effect on the microbiome.

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Metalign: Efficient alignment-based metagenomic profiling via containment min hash

10.1101/2020.01.17.910521 ◽

2020 ◽

Cited By ~ 1

Author(s):

Nathan LaPierre ◽

Mohammed Alser ◽

Eleazar Eskin ◽

David Koslicki ◽

Serghei Mangul

Keyword(s):

False Negative ◽

Environmental Data ◽

Reference Database ◽

Link Type ◽

Whole Genome Shotgun Sequencing ◽

Database Size ◽

Community Data ◽

Novel Method ◽

Relative Abundances

AbstractWhole-genome shotgun sequencing enables the analysis of microbial communities in unprecedented detail, with major implications in medicine and ecology. Predicting the presence and relative abundances of microbes in a sample, known as “metagenomic profiling”, is a critical first step in microbiome analysis. Existing profiling methods have been shown to suffer from poor false positive or false negative rates, while alignment-based approaches are often considered accurate but computationally infeasible. Here we present a novel method, Metalign, that addresses these concerns by performing efficient alignment-based metagenomic profiling. We use a containment min hash approach to reduce the reference database size dramatically before alignment and a method to estimate organism relative abundances in the sample by resolving reads aligned to multiple genomes. We show that Metalign achieves significantly improved results over existing methods on simulated datasets from a large benchmarking study, CAMI, and performs well on in vitro mock community data and environmental data from the Tara Oceans project. Metalign is freely available at https://github.com/nlapier2/Metalign, along with the results and plots used in this paper, and a docker image is also available at https://hub.docker.com/repository/docker/nlapier2/metalign.

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SCAPP: an algorithm for improved plasmid assembly in metagenomes

Microbiome ◽

10.1186/s40168-021-01068-z ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

David Pellow ◽

Alvah Zorea ◽

Maraike Probst ◽

Ori Furman ◽

Arik Segal ◽

...

Keyword(s):

Bacterial Species ◽

Bacterial Genome ◽

Biological Knowledge ◽

Assessment Procedure ◽

Metagenomic Sequencing ◽

Sequencing Data ◽

Human Gut ◽

Double Stranded Dna ◽

Wide Range ◽

Python Package

Abstract Background Metagenomic sequencing has led to the identification and assembly of many new bacterial genome sequences. These bacteria often contain plasmids: usually small, circular double-stranded DNA molecules that may transfer across bacterial species and confer antibiotic resistance. These plasmids are generally less studied and understood than their bacterial hosts. Part of the reason for this is insufficient computational tools enabling the analysis of plasmids in metagenomic samples. Results We developed SCAPP (Sequence Contents-Aware Plasmid Peeler)—an algorithm and tool to assemble plasmid sequences from metagenomic sequencing. SCAPP builds on some key ideas from the Recycler algorithm while improving plasmid assemblies by integrating biological knowledge about plasmids. We compared the performance of SCAPP to Recycler and metaplasmidSPAdes on simulated metagenomes, real human gut microbiome samples, and a human gut plasmidome dataset that we generated. We also created plasmidome and metagenome data from the same cow rumen sample and used the parallel sequencing data to create a novel assessment procedure. Overall, SCAPP outperformed Recycler and metaplasmidSPAdes across this wide range of datasets. Conclusions SCAPP is an easy to use Python package that enables the assembly of full plasmid sequences from metagenomic samples. It outperformed existing metagenomic plasmid assemblers in most cases and assembled novel and clinically relevant plasmids in samples we generated such as a human gut plasmidome. SCAPP is open-source software available from: https://github.com/Shamir-Lab/SCAPP.

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Competitive exclusion and metabolic dependency among microorganisms structure the cellulose economy of agricultural soil

10.21203/rs.2.23522/v1 ◽

2020 ◽

Author(s):

Roland C Wilhelm ◽

Charles Pepe-Ranney ◽

Pamela Weisenhorn ◽

Mary Lipton ◽

Daniel H. Buckley

Keyword(s):

Microbial Growth ◽

Competitive Exclusion ◽

Antibiotic Production ◽

Growth Dynamics ◽

Soil Disturbance ◽

Gliding Motility ◽

Cellulolytic Microorganisms ◽

Trade Offs ◽

Self Sufficiency ◽

Attachment Structures

Abstract Many cellulolytic microorganisms degrade cellulose through extracellular processes that yield free intermediates which promote interactions with non-cellulolytic organisms. We hypothesize that these interactions determine the ecological and physiological traits that govern the fate of cellulosic carbon (C) in soil. We evaluated the genomic potential of soil microorganisms that access C from 13 C-labeled cellulose. We used metagenomic-SIP and metaproteomics to evaluate whether cellulolytic and non-cellulolytic microbes that access 13 C from cellulose encode traits indicative of metabolic dependency or competitive exclusion. The most highly 13 C-enriched taxa were cellulolytic Cellvibrio ( Gammaproteobacteria ) and Chaetomium ( Ascomycota ), which exhibited a strategy of self-sufficiency (prototrophy), rapid growth, and competitive exclusion via antibiotic production. These ruderal taxa were common indicators of soil disturbance in agroecosystems, such as tillage and fertilization. Auxotrophy was more prevalent in cellulolytic Actinobacteria than in cellulolytic Proteobacteria , demonstrating differences in dependency among cellulose degraders. Non-cellulolytic taxa that accessed 13 C from cellulose ( Planctomycetales , Verrucomicrobia and Vampirovibrionales ) were highly dependent, as indicated by patterns of auxotrophy and 13 C-labeling (i.e. partial labelling or labeling at later-stages). Major 13 C-labeled cellulolytic microbes ( e.g. Sorangium, Actinomycetales, Rhizobiales and Caulobacteraceae ) possessed adaptations for surface colonization ( e.g. gliding motility, hyphae, attachment structures) signifying the importance of surface ecology in decomposition. These results suggest that access to cellulose was accompanied by ecological trade-offs characterized by differing degrees of metabolic dependency and competitive exclusion. These trade-offs likely influence microbial growth dynamics on particulate organic carbon and reveal that the fate of carbon is governed by a complex economy within the microbial community.

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Microbial growth dynamics on the basis of individual budgets

Quantitative Aspects of Growth and Metabolism of Microorganisms ◽

10.1007/978-94-011-2446-1_4 ◽

1992 ◽

pp. 159-174

Author(s):

S. A. L. M. Kooijman ◽

E. B. Muller ◽

A. H. Stouthamer

Keyword(s):

Microbial Growth ◽

Growth Dynamics

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Microbial growth dynamics

Comparative Biochemistry and Physiology Part A Physiology ◽

10.1016/0300-9629(91)90355-g ◽

1991 ◽

Vol 100 (4) ◽

pp. 1055

Keyword(s):

Microbial Growth ◽

Growth Dynamics

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Southern Chinese populations harbour non-nucleatum Fusobacteria possessing homologues of the colorectal cancer-associated FadA virulence factor

Gut ◽

10.1136/gutjnl-2019-319635 ◽

2020 ◽

Vol 69 (11) ◽

pp. 1998-2007 ◽

Cited By ~ 4

Author(s):

Yun Kit Yeoh ◽

Zigui Chen ◽

Martin C S Wong ◽

Mamie Hui ◽

Jun Yu ◽

...

Keyword(s):

Colorectal Cancer ◽

Fusobacterium Nucleatum ◽

Disease Status ◽

Rural Populations ◽

Microbial Genomes ◽

Microbiome Composition ◽

Chinese Populations ◽

Southern Chinese ◽

Relative Abundances ◽

Reference Genomes

ObjectiveFusobacteria are not common nor relatively abundant in non-colorectal cancer (CRC) populations, however, we identified multiple Fusobacterium taxa nearly absent in western and rural populations to be comparatively more prevalent and relatively abundant in southern Chinese populations. We investigated whether these represented known or novel lineages in the Fusobacterium genus, and assessed their genomes for features implicated in development of cancer.MethodsPrevalence and relative abundances of fusobacterial species were calculated from 3157 CRC and non-CRC gut metagenomes representing 16 populations from various biogeographies. Microbial genomes were assembled and compared with existing reference genomes to assess novel fusobacterial diversity. Phylogenetic distribution of virulence genes implicated in CRC was investigated.ResultsIrrespective of CRC disease status, southern Chinese populations harboured increased prevalence (maximum 39% vs 7%) and relative abundances (average 0.4% vs 0.04% of gut community) of multiple recognised and novel fusobacterial taxa phylogenetically distinct from Fusobacterium nucleatum. Genomes assembled from southern Chinese gut metagenomes increased existing fusobacterial diversity by 14.3%. Homologues of the FadA adhesin linked to CRC were consistently detected in several monophyletic lineages sister to and inclusive of F. varium and F. ulcerans, but not F. mortiferum. We also detected increased prevalence and relative abundances of F. varium in CRC compared with non-CRC cohorts, which together with distribution of FadA homologues supports a possible association with gut disease.ConclusionThe proportion of fusobacteria in guts of southern Chinese populations are higher compared with several western and rural populations in line with the notion of environment/biogeography driving human gut microbiome composition. Several non-nucleatum taxa possess FadA homologues and were enriched in CRC cohorts; whether this imposes a risk in developing CRC and other gut diseases deserves further investigation.

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