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Metagenomics

by Gregor Wolbring

January 15, 2009

Metagenomics is a term coined a decade ago for a field that has taken off in recent years, mostly due to advances in information, sequencing, and data analysis and mining technologies (see here).

The New Science of Metagenomics: Revealing the Secrets of Our Microbial Planet by the Committee on Metagenomics: Challenges and Functional Applications, U.S. National Research Council, is a book one should read if one is interested in the field. It describes metagenomics as follows: “Metagenomics in either sense will probably never be circumscribed tightly by a definition, and it would be undesirable to attempt to so limit it now, but the term includes cultivation-independent genome-level characterization of communities or their members, high-throughput gene-level studies of communities with methods borrowed from genomics, and other “omics” studies..., which are aimed at understanding transorganismal behaviors and the biosphere at the genomic level.”

The book envisions collaborations among academic disciplines including: atmospheric, ocean, soil, and water studies; geology; medicine; veterinary science; agricultural science; environment; and bioengineering. Metagenomics offers a means of solving practical problems facing humanity in earth sciences, life sciences, biomedical sciences, bioenergy, bioremediation, biotechnology, agriculture, biodefense and microbial forensics.

Metagenomics enables the study of the 99 percent or more of microbes that have never been cultured and might not be cultured. According to the committee that published the book, the 12 members of the USA Microbe Project -- the Department of Agriculture, the Department of Defense, the Department of Energy, the Department of Homeland Security, the Department of the Interior US Geological Survey, the Environmental Protection Agency, the Food and Drug Administration, the National Aeronautics and Space Administration, the National Institutes of Health, the National Institute of Standards and Technology, the National Oceanic and Atmospheric Administration, and the National Science Foundation along with the CIA and the FBI -- are the federal agencies likely to benefit further from advances in metagenomics.

In 2005 scientists, physicians, industry representatives, and administrators from funding agencies in Asia, the Americas, and Europe met in Paris met to discuss human metagenomic applications such as the human intestinal metagenome, and the International Human Gut Metagenome Initiative was born. Since then, more human applications have appeared.

Conference wise, if one looks at the conferences from 2003-2008, one sees the explosive growth of metagenomic scope and reach.

Metagenomics 2003 held in Germany, drew more than 250 participants from around the world. The topics were:
• accessing microbial diversity: novel techniques;
• genome analyses of uncultivated microorganisms;
• novel metabolic traits and pathways;
• comparative and functional genomics;
• enzymes and compounds from the metagenome: biotechnological applications;
• evolution of genomes and complexity; and
• constraints and conceptual needs of environmental genomics.

Metgenomics 2006 covered microbial ecology and evolution; functional metagenomics to capture the soil resistome; cyber metagenomics; microbial population and environmental genomics; strain genome, pangenome and metagenome: the case of  the square haloarchaeon; it's so nice to have a few trillion friends: exploring the structure and functions of our human gut microbiota and microbiome; microbial cyberinfrastructure; microbial evolution, functional metagenomics and biogeochemistry; microbial ocean metagenomics: the central dogma meets systems ecology; metagenomes and metaspecies; biogeochemistry first question: “how do microorganism-driven geochemical cycles affect structure and function of ecosystems?”; the 'axis of evol' and the uses of evolutionary analysis in metagenomic studies.

Metagenomics 2007 covered topics such as the emerging global community of microbial metagenomics researchers; standardization; medicine and human biology; medical metagenomics; computational metagenomics; applied metagenomics; environmental metagenomics; ecological metagenomics; evolution and population genetics.

Metagenomics 2008 was held in November at the California Institute for Telecommunications and Information Technology, University of California, San Diego, La Jolla, California, was the third annual Metagenomics conference organized by the UCSD-based Community Cyberinfrastructure for Advanced Microbial Ecology Research and Analysis (CAMERA) project. It included “research in microbial ecology, genomics and evolution, bioinformatics, and biogeochemistry, as well as research on multiple organisms interacting with each other and their environment; that is, on ecological genomics, population/ community genomics and environmental genomics.“ (Click here for webcasts from the conference.)

The scope of the 2008 conference was very broad, including: genomic and metagenomic metadata; setting the stage: mobilizing the metagenomics; CAMERA interest in community standards for the capture and exchange of metadata; overview of the Genome Standards Consortium (GSC) and the minimum information about a (meta) genome sequence (MIGS/MIMS); the rapidly Growing standards landscape in ‘omics'; core GSC projects; implementing MIGS/MIMS: the genomic contextual; strainInfo and the linkage of organisms, gene and genomes: the genomic rosetta stone; towards computer assisted markup of data; towards a standards compliant literature: the GSC ejournal; towards transparency of computational analyses: a central SOP repository; the importance of context for the design and interpretation of comparative metagenomics studies: the MINIMESS proposal ; should genomics contextual data fly coach? extending MIGS/MIMS to the description of  ribosomal RNA sequences; ontologies and the description of habitat and geolocation; metadata capture: a key step for advancing understanding; challenges in metagenomics for bioinformatics and computational biology; connecting metagenomics and metaproteomics; new sequence technologies for metagenomics; the metagenomic voyage: in situ to in silico; wellness and diseases: implications of important microbiota; soil options; the evolution of small bacterial genomes in the ultra-oligotrophic ocean; the importance of marine Alexandra Z. Worden, Monterey Bay Aquarium picoeukaryotes and the search for lost time; marine metagenomics; photosystem-I gene cassettes in marine phages; deep-ocean metagenomics: comparative investigations of microbes inhabiting hydrothermal vents and the cold deep ocean; metagenomic analysis of deep subsurface environments integrative marine metagenomics; new technologies in metagenomics; analyzing the mobilome using  metagenomics; electromicrobiolgy: novel approaches for investigating charge transfer and energy transformation in microbial systems; accessing the metatranscriptome for complex marine microbial communities; genome standards consortium report; integrated information system for genomic and metagenomic data analysis at NCBI; targeted gene Identification from short gene fragments in metagenome and their use in biogeochemical studies; metabolic characterization of Candidatus Accumulibacter Phosphatis using metaproteomic analysis; a genomic encyclopedia of bacteria and Archaea (GEBA) and the search for the dark matter of the biological universe; host-associated microbes; genomic and genetic insight into the gut; microbiota function and manipulation; new insights Into lignocellulose conversion by termite gut microbes; metaproteomics as a key technology for characterizing the human microbiome; metagenomic comparison of the microbial hindgut communities in drywood- and grass-feeding termites; screening of the human intestinal microbiota for the discovery of novel enzymes efficient for plant fiber; emerging sequence technologies; single molecule analyses of DNA in environmental microbes; new sequencing technologies at JGI and applications in bioenergy research; International Soil Metagenome Sequencing Project; exploring next generation sequencing today; connecting sequence, structure and function for metagenomics; the Human Microbiome Project: key questions/challenges diversity profile of the human skin microbiome in health and disease; the human oral microbiome; metabonomic profiling of the gut microbiome: implications for human health; getting to molecular and bacterial community function; structural genomics (SG) and beginning a research dialogue with the metagenomics community; protein target selection challenges and charge to discussion groups; role of structure in ascertaining functional properties of microbial communities: how can these two research domains interact most productively?

The Choice is Yours

Metagenomics seems to be another player in the convergence arena, being linked to metatranscriptomics; metaproteomics; synthetic biology; geo-engineering; bioinformatics; information technology; sequencing technologies; data mining; and even paleogenomics. It has the potential for many possible positive discoveries according to the committee on metagenomics of the US National Research Council. Metagenomic approaches have the potential to identify new or improved biosynthetic pathways and processes for production of valuable biomolecules, according to Genome Canada. There are now requests that metagenomics be included in high school curricula.

The US National Research Council committee on metagenomics recommends, among other things, establishing a Global Metagenomics Initiative that includes a small number of large-scale, comprehensive projects that use metagenomics to understand model microbial communities, a larger number of mid-sized projects, and many small projects. The committee suggests integrating public communication into graduate training and teaching graduate students the principles of effective public outreach. Unfortunately, the report has a limited view on who the major stakeholders are, not mentioning the public at all.

Metagenomics also raises questions. The US National Research Council committee identifies  as metagenomics E3LS issues regulatory concerns around taxonomies and the definition and meaning of species put into question with the metagenomic approach; patent issues; compliance with the Convention on Biological Diversity; biosafety; and data release and dissemination.

According to Genome Canada, the “metagenomic approach raises profound ontological questions about the object of its study: are there genuine entities, metagenomes, being described by the science? If so, is the individual organism a less fundamental unit of biological analysis than has been supposed? What would that mean for the unquestioned assumptions of many biologists and commentators on biology about ‘one genome, one organism?' These are not marginal questions because most organisms, whether measured by mass or by numbers, are single celled and are the only kinds of organisms that have existed for most of the history of life. Animals and plants are very much the oddities, therefore, and yet many general notions of biology, including  philosophical ones, consider only these visible forms of life. Most current conceptions of biodiversity make little attempt to account for the large majority of its obvious subject matter: the diverse microbial world that pervades every level of macroorganismal existence. Evolutionarily, the tenets of neoDarwinism need radical expansion to incorporate processes and outcomes such as lateral gene transfer, and philosophers of evolution have a great deal of work to do to catch up with debates in the biology. The notion of reproductive isolation due to geographic barriers, for example, still figures largely in many discussions of the species problem, but geography is often deemed to have little relevance to microorganisms. New genomic data, however, have generated unexpected findings of geographical patterns in the distribution of microbial populations (rather than exclusively ecological patterns) but the relationship between the interplay of geographical and ecological factors in microbial biodiversity needs much more investigation. Such findings raise further philosophical questions about how separately or similarly we regard biological theories about macrobes and microbes.”

There is a need to assess the potential impact of policies on the project, and possible regulations emerging from the international dialogue on these issues.

Gregor Wolbring is a biochemist, bioethicist, science and technology ethicist, disability/vari-ability studies scholar, and health policy and science and technology studies researcher at the University of Calgary. He is a member of the Center for Nanotechnology and Society at Arizona State University; Member CAC/ISO - Canadian Advisory Committees for the International Organization for Standardization section TC229 Nanotechnologies; Member of the editorial team for the Nanotechnology for Development portal of the Development Gateway Foundation; Chair of the Bioethics Taskforce of Disabled People's International; and Member of the Executive of the Canadian Commission for UNESCO. He publishes the Bioethics, Culture and Disability website, moderates a weblog for the International Network for Social Research on Diasbility, and authors a weblog on NBICS and its social implications.

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Please contact the author for information on this reference
or for additional future references at gwolbrin@ucalgary.ca


© Gregor Wolbring, All Rights Reserved, 2009. Please contact the author for permission to reprint.

 

   
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