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Systems Biology

Functional analysis of natural microbial consortia using community proteomics

Key Points

  • Microbial communities, rather than individual microorganisms, carry out important functions. However, it is difficult to probe metabolism in communities.

  • Proteogenomics has excellent potential for studying the physiology, ecology and evolution of microbial populations and communities.

  • Microbial proteomics currently makes use of both gel-based and gel-independent liquid chromatography-based separations, and relies on mass spectrometry-based peptide identification. The full proteomics process is discussed.

  • With isolates grown under different metabolic conditions, it is possible to quantitatively compare thousands of proteins from the different growth conditions. By analysing microbial isolates from multiple growth states, between 50–90% of the predicted proteome can be identified.

  • Proteogenomics has been used to analyse an acid mine drainage community, and to study wastewater sludge microbial communities that are used for the removal of biological phosphorus. Strain-resolved proteogenomics analyses can be used to infer partitioning of strain variants in microniches of members of simple communities.

  • Initial success in analysing proteomes from complex communities, such as the human microbiome, are discussed, but new analysis methods are required to analyse complex communities such as those found in the oceans. New methods are also required to analyse tiny samples.

Abstract

We know very little about the metabolic functioning and evolutionary dynamics of microbial communities. Recent advances in comprehensive, sequencing-based methods, however, are laying a molecular foundation for new insights into how microbial communities shape the Earth's biosphere. Here we explore the convergence of microbial ecology, genomics, biological mass spectrometry and informatics that form the new field of microbial community proteogenomics. We discuss the first applications of proteogenomics and its potential for studying the physiology, ecology and evolution of microbial populations and communities.

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Figure 1: Liquid chromatography–mass spectrometry-based proteomics.
Figure 2: Relationship between species abundance, protein identification levels and protein coverage.

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Acknowledgements

Funding was provided by the United States Department of Energy: Genomics: Genomes-to-Life Program, the National Science Foundation Biocomplexity Program and the NASA Astrobiology Institute. B. R. Maggard is thanked for secretarial assistance in the preparation of this manuscript. Oak Ridge National Laboratory is managed by University of Tennessee–Battelle LLC for the Department of Energy under contract DOE-AC05-00OR22725.

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Correspondence to Nathan C. VerBerkmoes.

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DATABASES

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Accumulibacter phosphatis

FURTHER INFORMATION

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DOE Genomics:GTL

Integrated Microbial Genomes with Microbiome Samples

The Human Microbiome Project

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Glossary

Consortia

A coexisting group of microbial populations.

Metaproteomics

The term metaproteomics is preferred for more partial, gene-centric approaches to community analysis.

Community proteomics

Application of proteomics beyond single isolate studies aimed at comprehensive system analysis.

Community proteogenomics

A dynamic interplay between community genomics and community proteomics, where the genomic makeup of the populations is inferred from the proteomics data, allowing for evolutionary analyses as well as for a valid interpretation of proteomics data from genomically uncharacterized samples.

Mass spectrometry-based proteomics

The application of mass spectrometry to proteome measurements.

Tandem mass spectrometry

The isolation, activation and fragmentation of peptides in mass spectrometers to obtain primary sequence information about the peptides.

Proteome bioinformatics

A subdiscipline in proteomics that is concerned with all methods of data analyses, validation, comparisons, statistics, dissemination and archival.

Binning methods

Methods used in metagenomics to group sequencing reads and assembled sequence contigs by the organism that they come from.

De novo sequencing or sequence tagging

Attempting to obtain full or partial sequences directly from tandem mass spectra without the use of a genome or proteome database.

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VerBerkmoes, N., Denef, V., Hettich, R. et al. Functional analysis of natural microbial consortia using community proteomics. Nat Rev Microbiol 7, 196–205 (2009). https://doi.org/10.1038/nrmicro2080

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