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A review of scientific research into Metagenomics: the study of uncultured microorganisms.

Next-generation Sequencing
Edited by: Jianping Xu
The most recent advances in NGS instrumentation and data analysis, current NGS platforms, sequencing chemistries, instrument specifications, general workflows and procedures.
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Adapted from Marco et al. in Metagenomics
The advent of metagenomics has had a dramatic effect in the way we view and study the microbial world. By allowing the direct investigation of the vast majority of bacteria, as well as viruses and fungi, irrespective of their culturability and taxonomic identities, metagenomics has not only changed microbiological theory and methods but also has challenged the classical concept of species. This newly evolved biological field has proven to be rich and comprehensive and is making important contributions to microbial ecology, biodiversity, bioremediation, bioprospection of natural products, medicine, and many other fields. The diversity of facets of metagenomics as well as the multiplicity of its potential applications makes it difficult to find an ample but at the same time ordered account of this new discipline.
Suggested reading:   Metagenomics: Current Innovations and Future Trends

Genomics and Metagenomics

Adapted from Nelson et al. in Environmental Molecular Microbiology
The extensive suite of molecular-based approaches developed over the past decade has enabled the field of metagenomics, the study of uncultured microorganisms. Paramont to metagenomic analysis is use of high-throughput DNA sequencing technologies, which with the advent of low cost next-generation methods is transforming metagenomics. The application of metagenomics, to both global environments and microbes associated with a living host, has facilitated study of the functional ecology of environmental microorganisms. Novel functional genes and environmental functional signatures can be retrieved using metagenomics, and these can form the basis of hypothesis driven analyses of uncultured microorganisms. A with any technology, the daunting task is to understand and apply the growing number of metagenomics sequences in the context of microbial ecology and evolution.
Suggested reading:   Metagenomics: Current Innovations and Future Trends


Adapted from Dill et al. in Environmental Molecular Microbiology
Microbial ecology is currently experiencing a renaissance spurred by the rapid development of molecular techniques and "omics" technologies in particular. As never before, these tools have allowed researchers in the field to produce a massive amount of information through in situ measurements and analysis of natural microbial communities, both vital approaches to the goal of unraveling the interactions of microbes with their environment and with one another. While genomics can provide information regarding the genetic potential of microbes, proteomics characterizes the primary end-stage product, proteins, thus conveying functional information concerning microbial activity. Advances in mass spectrometry instrumentation and methodologies, along with bioinformatics approaches, have brought this analytic chemistry technique to relevance in the biological realm due to its powerful applications in proteomics. Mass spectrometry-enabled proteomics, including "bottom-up" and "top-down" approaches, is capable of supplying a wealth of biologically-relevant information, from simple protein cataloging of the proteome of a microbial community to identifying post-translational modifications of individual proteins.
Suggested reading:   Metagenomics: Current Innovations and Future Trends

Application of Metagenomics to Bioremediation

Adapted from George et al. in Metagenomics
Metagenomics can improve strategies for monitoring the impact of pollutants on ecosystems and for cleaning up contaminated environments. Increased understanding of how microbial communities cope with pollutants will help assess the potential of contaminated sites to recover from pollution and increase the chances of bioaugmentation or biostimulation trials to succeed. Moreover, by providing direct access to the pool of environmental genomes without the bias of cultivation, metagenomics offers the possibility of exploring the vast diversity of degradation pathways of environmental microorganisms. This could lead to the design of more efficient customized strains/consortia for targeted use in bioremediation applications.
Suggested reading:   Metagenomics: Current Innovations and Future Trends

Applications of Metagenomics to Industrial Bioproducts

Adapted from Wong, D. in Metagenomics
Recent progress in mining the rich genetic resource of non-culturable microbes has led to the discovery of new genes, enzymes, and natural products. The impact of metagenomics is witnessed in the development of commodity and fine chemicals, agrochemicals and pharmaceuticals where the benefit of enzyme-catalyzed chiral synthesis is increasingly recognized. Recovery of metabolic pathways and gene clusters involved in biosynthesis of antibiotics and bioactive molecules has increased the prospect of identifying useful natural and synthetic products for drug development. The discovery of biocatalysts operating optimally with high efficiency in conditions amenable to industrial processes requirements are key to successful development of food products, detergent additives, bioactive compounds, fuel alcohol and biodiesel, as well as optically active intermediates for chemical and drug synthesis.
Suggested reading:   Metagenomics: Current Innovations and Future Trends

Applications of Metagenomics to the Human Microbiome

Adapted from Nelson and White in Metagenomics
Genomics came of age when we began to witness a greater level of microbial diversity within species than previously anticipated. This laid the foundation for generating genomic sequence data from whole environments without first using a culturing step, a field of research now known as metagenomics. Metagenomics can be defined as the genomic analysis of microorganisms by direct extraction and cloning of DNA from an assemblage of microorganisms. The availability of next generation sequencing technologies such as 454 pyrosequencing have made it such that a cloning step is no longer essential for metagenomic projects. The National Institutes of Health launched a Human Microbiome initiative with primary goals to determine if there is a core human microbiome, to understand the changes in the human microbiome that can be correlated with human health, and to develop new technological and bioinformatics tools to support these goals. Initial sequencing initiatives for this program are in place and include metagenomic sequencing to characterize the microbial communities from 15-18 body sites from at least 250 individuals. This effort has expanded to become a worldwide initiative.
Suggested reading:   Metagenomics: Current Innovations and Future Trends

Applications of Metagenomics in Plant-microbe Interactions

Adapted from Charles, T. in Metagenomics
The interactions between microbes and plants make the major contribution to the biotic components of soils, the most diverse habitats on Earth. Plants play central roles in providing nutrient input into the soil, both through microbially-mediated decomposition of plant matter, and through the direct provision of photosynthate derived root exudates. These nutrients support large and diverse microbial communities, many of which provide direct benefit to the plant. The interplay between plants and their microbial co-habitants is regulated by extensive chemical signalling. Most of what we know about these complex community interactions has been derived through study of organisms in pure culture, but it is well known that the vast majority of microbes have not been cultivated. We now have the opportunity to explore the interactions between plants and microbes through cultivation-independent study of the microbial communities. While high-throughput DNA sequence analysis is an important tool for these studies, the immense richness and diversity of such communities present a strong mandate for the use of functional metagenomics strategies that involve a broad variety of screening methodologies to discover and study the currently unknown key biological processes.
Suggested reading:   Metagenomics: Current Innovations and Future Trends

Further reading