Single-cell metagenomics: challenges and applications

Xu, Yuan; Zhao, Fangqing

doi:10.1007/s13238-018-0544-5

Cited by 73 publications

(59 citation statements)

References 78 publications

(93 reference statements)

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“…The functional predictions generated for the species pan-genomes could also be leveraged to develop new culturing strategies for isolation of candidate species. Target-enrichment methods such as single-cell 39 and/or bait-capture hybridization 40 approaches could also be applied. Being able to enrich for specific groups of interest, even without culturing, could allow recovery of better-quality versions of MAGs and improve the analysis derived from genome sequence data alone.…”

Section: Discussionmentioning

confidence: 99%

A unified sequence catalogue of over 280,000 genomes obtained from the human gut microbiome

Almeida

Nayfach

Boland

et al. 2019

Preprint

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26Comprehensive reference data is essential for accurate taxonomic and functional 27 characterization of the human gut microbiome. Here we present the Unified Human 28Gastrointestinal Genome (UHGG) collection, a resource combining 286,997 genomes 29 representing 4,644 prokaryotic species from the human gut. These genomes contain over 625 30 million protein sequences used to generate the Unified Human Gastrointestinal Protein 31 (UHGP) catalogue, a collection that more than doubles the number of gut protein clusters over 32 the Integrated Gene Catalogue. We find that a large portion of the human gut microbiome 33 remains to be fully explored, with over 70% of the UHGG species lacking cultured 34 representatives, and 40% of the UHGP missing meaningful functional annotations. Intra-35 species genomic variation analyses revealed a large reservoir of accessory genes and single-36 nucleotide variants, many of which were specific to individual human populations. These freely 37 available genomic resources should greatly facilitate investigations into the human gut 38 microbiome. 39 3 Main 40 The human gut microbiome has been implicated in important phenotypes related to human 41 health and disease 1,2 . However, incomplete reference data that are missing microbial diversity 3 42 hamper our understanding of the roles of individual microbiome species, their interactions and 43 functions. Hence, establishing a comprehensive collection of microbial reference genomes and 44 genes is an important step for accurate characterization of the taxonomic and functional 45 repertoire of the intestinal microbial ecosystem. 46 47The Human Microbiome Project (HMP) 4 was a pioneering initiative to enrich our knowledge ( Supplementary Fig. 2), a standardized taxonomic framework based on a concatenated protein 112 phylogeny representing >140,000 public prokaryote genomes, fully resolved to the species 113 level (see 'Methods' for details on the taxonomy nomenclature used). However, over 60% of 114 6 the gut genomes could not be assigned to an existing species, confirming the majority of the 115 UHGG species lack representation in current reference databases. 116 117 Comparison of species recovered in individual studies 118We investigated how many of the 4,644 gut species were found in the different study 119 collections in order to determine their level of overlap and reproducibility, as well as the ratio 120 between cultured and uncultured species (Fig. 2a). The largest intersection was between the 121 collections of MAGs, with the same 1,081 species detected independently in the CIBIO, EBI 122 and HGM datasets, but not in any of the cultured genome studies. By restricting the analysis to 123 genomes recovered from 1,554 samples common to all three MAG studies, we found that 93-124 97% of species from each set were detected in at least one other MAG collection, and 79-86% 125 across all three ( Supplementary Fig. 3a). Similar level of species overlap was observed when 126 comparing studies on a per-sample basis ( Supplementary Fig. 3b). F...

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Section: Discussionmentioning

confidence: 99%

A unified sequence catalogue of over 280,000 genomes obtained from the human gut microbiome

Almeida

Nayfach

Boland

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…With the development of sequencing technologies and data analysis methods, several achievements in microbiome research have been made in recent years. [ 1 – 3 ] These include compelling discoveries in the field of medicine such as associations between the microbiome and metabolic diseases, [ 4 – 6 ] digestive diseases, [ 7 – 10 ] and cardiovascular diseases. [ 11 ] These developments and discoveries have increased the interest of physicians on microbiome research, with a dramatic increase in the number of publications in the field.…”

Section: Introductionmentioning

confidence: 99%

A guide to human microbiome research: study design, sample collection, and bioinformatics analysis

Qian

Chen

et al. 2020

Chinese Medical Journal

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The purpose of this review is to provide medical researchers, especially those without a bioinformatics background, with an easy-to-understand summary of the concepts and technologies used in microbiome research. First, we define primary concepts such as microbiota, microbiome, and metagenome. Then, we discuss study design schemes, the methods of sample size calculation, and the methods for improving the reliability of research. We emphasize the importance of negative and positive controls in this section. Next, we discuss statistical analysis methods used in microbiome research, focusing on problems with multiple comparisons and ways to compare β-diversity between groups. Finally, we provide step-by-step pipelines for bioinformatics analysis. In summary, the meticulous study design is a key step to obtaining meaningful results, and appropriate statistical methods are important for accurate interpretation of microbiome data. The step-by-step pipelines provide researchers with insights into newly developed bioinformatics analysis methods.

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“…Until improved technologies become available, completing the assembly of the microbial genomes and transcriptomes for most species likely requires a combination of approaches such as reconstruction from multiple homologous cells if available or additional metagenomic data. Metagenomic reads and contigs can be used to recover missing genomic regions and greatly improve the SAG assemblies (Dodsworth et al 2013 ; Nurk et al 2013 ; Becraft et al 2016 ; Xu and Zhao 2018 ). Likewise, metagenomic bins can also be improved by SAG datasets (Pachiadaki et al 2019 ).…”

Section: Technical Problems Recent Advances and Future Challengesmentioning

confidence: 99%

Microbial single-cell omics: the crux of the matter

Kaster

Sobol

2020

Appl Microbiol Biotechnol

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Single-cell genomics and transcriptomics can provide reliable context for assembled genome fragments and gene expression activity on the level of individual prokaryotic genomes. These methods are rapidly emerging as an essential complement to cultivation-based, metagenomics, metatranscriptomics, and microbial community-focused research approaches by allowing direct access to information from individual microorganisms, even from deep-branching phylogenetic groups that currently lack cultured representatives. Their integration and binning with environmental 'omics data already provides unprecedented insights into microbial diversity and metabolic potential, enabling us to provide information on individual organisms and the structure and dynamics of natural microbial populations in complex environments. This review highlights the pitfalls and recent advances in the field of single-cell omics and its importance in microbiological and biotechnological studies. Key points • Single-cell omics expands the tree of life through the discovery of novel organisms, genes, and metabolic pathways. • Disadvantages of metagenome-assembled genomes are overcome by single-cell omics. • Functional analysis of single cells explores the heterogeneity of gene expression. • Technical challenges still limit this field, thus prompting new method developments.

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Single-cell metagenomics: challenges and applications

Cited by 73 publications

References 78 publications

A unified sequence catalogue of over 280,000 genomes obtained from the human gut microbiome

A unified sequence catalogue of over 280,000 genomes obtained from the human gut microbiome

A guide to human microbiome research: study design, sample collection, and bioinformatics analysis

Microbial single-cell omics: the crux of the matter

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