The proportion of conserved DNA sequences with no clear function is steadily growing in bioinformatics databases. Studies of sequence and structural homology have indicated that many uncharacterized protein domain sequences are variants of functionally described domains. If these variants promote an organism's ecological fitness, they are likely to be conserved in the genome of its progeny and the population at large. The genetic composition of microbial communities in their native ecosystems is accessible through metagenomics. We hypothesize the co-variation of protein domain sequences across metagenomes from similar ecosystems will provide insights into their potential roles and aid further investigation.
We calculated the correlation of Pfam protein domain sequences across the Global Ocean Sampling metagenome collection, employing conservative detection and correlation thresholds to limit results to well-supported hits and associations. We then examined intercorrelations between domains of unknown function (DUFs) and domains involved in known metabolic pathways using network visualization and cluster-detection tools. We used a cautious “guilty-by-association” approach, referencing knowledge-level resources to identify and discuss associations that offer insight into DUF function. We observed numerous DUFs associated to photobiologically active domains and prevalent in the Cyanobacteria. Other clusters included DUFs associated with DNA maintenance and repair, inorganic nutrient metabolism, and sodium-translocating transport domains. We also observed a number of clusters reflecting known metabolic associations and cases that predicted functional reclassification of DUFs.
Critically examining domain covariation across metagenomic datasets can grant new perspectives on the roles and associations of DUFs in an ecological setting. Targeted attempts at DUF characterization in the laboratory or in silico may draw from these insights and opportunities to discover new associations and corroborate existing ones will arise as more large-scale metagenomic datasets emerge.
Following up on efforts from two earlier workshops, a meeting was convened in San Diego to (a) establish working connections between experts in the use of the Darwin Core and the GSC MIxS standards, (b) conduct mutual briefings to promote knowledge exchange and to increase the understanding of the two communities’ approaches, constraints, community goals, subtleties, etc., (c) perform an element-by-element comparison of the two standards, assessing the compatibility and complementarity of the two approaches, (d) propose and consider possible use cases and test beds in which a joint annotation approach might be tried, to useful scientific effect, and (e) propose additional action items necessary to continue the development of this joint effort. Several focused working teams were identified to continue the work after the meeting ended.
The Global Biodiversity Information Facility and the Genomic Standards Consortium convened a joint workshop at the University of Oxford, 27-29 February 2012, with a small group of experts from Europe, USA, China and Japan, to continue the alignment of the Darwin Core with the MIxS and related genomics standards. Several reference mappings were produced as well as test expressions of MIxS in RDF. The use and management of controlled vocabulary terms was considered in relation to both GBIF and the GSC, and tools for working with terms were reviewed. Extensions for publishing genomic biodiversity data to the GBIF network via a Darwin Core Archive were prototyped and work begun on preparing translations of the Darwin Core to Japanese and Chinese. Five genomic repositories were identified for engagement to begin the process of testing the publishing of genomic data to the GBIF network commencing with the SILVA rRNA database.
At the GSC11 meeting (4-6 April 2011, Hinxton, England, the GSC’s genomic biodiversity working group (GBWG) developed an initial model for a data management testbed at the interface of biodiversity with genomics and metagenomics. With representatives of the Global Biodiversity Information Facility (GBIF) participating, it was agreed that the most useful course of action would be for GBIF to collaborate with the GSC in its ongoing GBWG workshops to achieve common goals around interoperability/data integration across (meta)-genomic and species level data. It was determined that a quick comparison should be made of the contents of the Darwin Core (DwC) and the GSC data checklists, with a goal of determining their degree of overlap and compatibility. An ad-hoc task group lead by Renzo Kottman and Peter Dawyndt undertook an initial comparison between the Darwin Core (DwC) standard used by the Global Biodiversity Information Facility (GBIF) and the MIxS checklists put forward by the Genomic Standards Consortium (GSC). A term-by-term comparison showed that DwC and GSC concepts complement each other far more than they compete with each other. Because the preliminary analysis done at this meeting was based on expertise with GSC standards, but not with DwC standards, the group recommended that a joint meeting of DwC and GSC experts be convened as soon as possible to continue this joint assessment and to propose additional work going forward.
Building on the planning efforts of the RCN4GSC project, a workshop was convened in San Diego to bring together experts from genomics and metagenomics, biodiversity, ecology, and bioinformatics with the charge to identify potential for positive interactions and progress, especially building on successes at establishing data standards by the GSC and by the biodiversity and ecological communities. Until recently, the contribution of microbial life to the biomass and biodiversity of the biosphere was largely overlooked (because it was resistant to systematic study). Now, emerging genomic and metagenomic tools are making investigation possible. Initial research findings suggest that major advances are in the offing. Although different research communities share some overlapping concepts and traditions, they differ significantly in sampling approaches, vocabularies and workflows. Likewise, their definitions of ‘fitness for use’ for data differ significantly, as this concept stems from the specific research questions of most importance in the different fields. Nevertheless, there is little doubt that there is much to be gained from greater coordination and integration. As a first step toward interoperability of the information systems used by the different communities, participants agreed to conduct a case study on two of the leading data standards from the two formerly disparate fields: (a) GSC’s standard checklists for genomics and metagenomics and (b) TDWG’s Darwin Core standard, used primarily in taxonomy and systematic biology.
Here we present a standard developed by the Genomic Standards Consortium (GSC) for reporting marker gene sequences—the minimum information about a marker gene sequence (MIMARKS). We also introduce a system for describing the environment from which a biological sample originates. The ‘environmental packages’ apply to any genome sequence of known origin and can be used in combination with MIMARKS and other GSC checklists. Finally, to establish a unified standard for describing sequence data and to provide a single point of entry for the scientific community to access and learn about GSC checklists, we present the minimum information about any (x) sequence (MIxS). Adoption of MIxS will enhance our ability to analyze natural genetic diversity documented by massive DNA sequencing efforts from myriad ecosystems in our ever-changing biosphere.
State of the art (DNA) sequencing methods applied in “Omics” studies grant insight into the ‘blueprints’ of organisms from all domains of life. Sequencing is carried out around the globe and the data is submitted to the public repositories of the International Nucleotide Sequence Database Collaboration. However, the context in which these studies are conducted often gets lost, because experimental data, as well as information about the environment are rarely submitted along with the sequence data. If these contextual or metadata are missing, key opportunities of comparison and analysis across studies and habitats are hampered or even impossible. To address this problem, the Genomic Standards Consortium (GSC) promotes checklists and standards to better describe our sequence data collection and to promote the capturing, exchange and integration of sequence data with contextual data. In a recent community effort the GSC has developed a series of recommendations for contextual data that should be submitted along with sequence data. To support the scientific community to significantly enhance the quality and quantity of contextual data in the public sequence data repositories, specialized software tools are needed. In this work we present CDinFusion, a web-based tool to integrate contextual and sequence data in (Multi)FASTA format prior to submission. The tool is open source and available under the Lesser GNU Public License 3. A public installation is hosted and maintained at the Max Planck Institute for Marine Microbiology at http://www.megx.net/cdinfusion. The tool may also be installed locally using the open source code available at http://code.google.com/p/cdinfusion.
DNA-binding transcription factors (TFs) regulate cellular functions in prokaryotes, often in response to environmental stimuli. Thus, the environment exerts constant selective pressure on the TF gene content of microbial communities. Recently a study on marine Synechococcus strains detected differences in their genomic TF content related to environmental adaptation, but so far the effect of environmental parameters on the content of TFs in bacterial communities has not been systematically investigated.
We quantified the effect of environment stability on the transcription factor repertoire of marine pelagic microbes from the Global Ocean Sampling (GOS) metagenome using interpolated physico-chemical parameters and multivariate statistics. Thirty-five percent of the difference in relative TF abundances between samples could be explained by environment stability. Six percent was attributable to spatial distance but none to a combination of both spatial distance and stability. Some individual TFs showed a stronger relationship to environment stability and space than the total TF pool.
Environmental stability appears to have a clearly detectable effect on TF gene content in bacterioplanktonic communities described by the GOS metagenome. Interpolated environmental parameters were shown to compare well to in situ measurements and were essential for quantifying the effect of the environment on the TF content. It is demonstrated that comprehensive and well-structured contextual data will strongly enhance our ability to interpret the functional potential of microbes from metagenomic data.
transcription factors; ecological metagenomics; interpolated environmental data; multivariate statistics
A vast and rich body of information has grown up as a result of the world's enthusiasm for 'omics technologies. Finding ways to describe and make available this information that maximise its usefulness has become a major effort across the 'omics world. At the heart of this effort is the Genomic Standards Consortium (GSC), an open-membership organization that drives community-based standardization activities, Here we provide a short history of the GSC, provide an overview of its range of current activities, and make a call for the scientific community to join forces to improve the quality and quantity of contextual information about our public collections of genomes, metagenomes, and marker gene sequences.
In any sequencing project, the possible depth of comparative analysis is determined largely by the amount and quality of the accompanying contextual data. The structure, content, and storage of this contextual data should be standardized to ensure consistent coverage of all sequenced entities and facilitate comparisons. The Genomic Standards Consortium (GSC) has developed the “Minimum Information about Genome/Metagenome Sequences (MIGS/MIMS)” checklist for the description of genomes and here we annotate all 30 publicly available marine bacteriophage sequences to the MIGS standard. These annotations build on existing International Nucleotide Sequence Database Collaboration (INSDC) records, and confirm, as expected that current submissions lack most MIGS fields. MIGS fields were manually curated from the literature and placed in XML format as specified by the Genomic Contextual Data Markup Language (GCDML). These “machine-readable” reports were then analyzed to highlight patterns describing this collection of genomes. Completed reports are provided in GCDML. This work represents one step towards the annotation of our complete collection of genome sequences and shows the utility of capturing richer metadata along with raw sequences.
marine phages; contextual data; genome standards; markup language
In the future, we hope to see an open and thriving data market in which users can find and select data from a wide range of data providers. In such an open access market, data are products that must be packaged accordingly. Increasingly, eCommerce sellers present heterogeneous product lines to buyers using faceted browsing. Using this approach we have developed the Ontogrator platform, which allows for rapid retrieval of data in a way that would be familiar to any online shopper. Using Knowledge Organization Systems (KOS), especially ontologies, Ontogrator uses text mining to mark up data and faceted browsing to help users navigate, query and retrieve data. Ontogrator offers the potential to impact scientific research in two major ways: 1) by significantly improving the retrieval of relevant information; and 2) by significantly reducing the time required to compose standard database queries and assemble information for further research. Here we present a pilot implementation developed in collaboration with the Genomic Standards Consortium (GSC) that includes content from the StrainInfo, GOLD, CAMERA, Silva and Pubmed databases. This implementation demonstrates the power of ontogration and highlights that the usefulness of this approach is fully dependent on both the quality of data and the KOS (ontologies) used. Ideally, the use and further expansion of this collaborative system will help to surface issues associated with the underlying quality of annotation and could lead to a systematic means for accessing integrated data resources.
This report summarizes the proceedings of the 10th workshop of the Genomic Standards Consortium (GSC), held at Argonne National Laboratory, IL, USA. It was the second GSC workshop to have open registration and attracted over 60 participants who worked together to progress the full range of projects ongoing within the GSC. Overall, the primary focus of the workshop was on advancing the M5 platform for next-generation collaborative computational infrastructures. Other key outcomes included the formation of a GSC working group focused on MIGS/MIMS/MIENS compliance using the ISA software suite and the formal launch of the GSC Developer Working Group. Further information about the GSC and its range of activities can be found at http://gensc.org/.
This report summarizes the proceedings of the first day of the Metagenomics, Metadata and MetaAnalysis (M3) workshop held at the Intelligent Systems for Molecular Biology 2010 conference. The second day, which was dedicated to the inaugural meeting of the BioSharing initiative is presented in a separate report. The Genomic Standards Consortium (GSC) hosted the first day of this Special Interest Group (SIG) at ISMB to continue exploring the bottlenecks and emerging solutions for obtaining biological insights through large-scale comparative analysis of metagenomic datasets. The M3 SIG included invited and selected talks and a panel discussion at the end of the day involving the plenary speakers. Further information about the GSC and its range of activities can be found at http://gensc.org. Information about the newly established BioSharing effort can be found at http://biosharing.org/.
This report summarizes the proceedings of the 9th workshop of the Genomic Standards Consortium (GSC), held at the J. Craig Venter Institute, Rockville, MD, USA. It was the first GSC workshop to have open registration and attracted over 90 participants. This workshop featured sessions that provided overviews of the full range of ongoing GSC projects. It included sessions on Standards in Genomic Sciences, the open access journal of the GSC, building standards for genome annotation, the M5 platform for next-generation collaborative computational infrastructures, building ties with the biodiversity research community and two discussion panels with government and industry participants. Progress was made on all fronts, and major outcomes included the completion of the MIENS specification for publication and the formation of the Biodiversity working group.
This report summarizes the proceedings of the one day BioSharing meeting held at the Intelligent Systems for Molecular Biology (ISMB) 2010 conference in Boston, MA, USA This inaugural BioSharing event was hosted by the Genomic Standards Consortium as part of its M3 & BioSharing special interest group (SIG) workshop. The BioSharing event included invited talks from a range of community leaders and a panel discussion at the end of the day. The panel session led to the formal agreement among community leaders to join together to promote cross-community knowledge exchange and collaborations. A key focus of the newly formed Biosharing community will be linking up resources to promote real-world data sharing (virtuous cycle of data) and supporting compliance with data policies through the creation of a one-stop-portal of information. Further information about the newly established BioSharing effort can be found at http://biosharing.org.
This report summarizes the proceedings of the 8th meeting of the Genomic Standards Consortium held at the Department of Energy Joint Genome Institute in Walnut Creek, CA, USA on September 9-11, 2009. This three-day workshop marked the maturing of Genomic Standards Consortium from an informal gathering of researchers interested in developing standards in the field of genomic and metagenomics to an established community with a defined governance mechanism, its own open access journal, and a family of established standards for describing genomes, metagenomes and marker studies (i.e. ribosomal RNA gene surveys). There will be increased efforts within the GSC to reach out to the wider scientific community via a range of new projects. Further information about the GSC and its activities can be found at http://gensc.org/.
Environmental sequence datasets are increasing at an exponential rate; however, the vast majority of them lack appropriate descriptors like sampling location, time and depth/altitude: generally referred to as metadata or contextual data. The consistent capture and structured submission of these data is crucial for integrated data analysis and ecosystems modeling. The application MetaBar has been developed, to support consistent contextual data acquisition.
MetaBar is a spreadsheet and web-based software tool designed to assist users in the consistent acquisition, electronic storage, and submission of contextual data associated to their samples. A preconfigured Microsoft® Excel® spreadsheet is used to initiate structured contextual data storage in the field or laboratory. Each sample is given a unique identifier and at any stage the sheets can be uploaded to the MetaBar database server. To label samples, identifiers can be printed as barcodes. An intuitive web interface provides quick access to the contextual data in the MetaBar database as well as user and project management capabilities. Export functions facilitate contextual and sequence data submission to the International Nucleotide Sequence Database Collaboration (INSDC), comprising of the DNA DataBase of Japan (DDBJ), the European Molecular Biology Laboratory database (EMBL) and GenBank. MetaBar requests and stores contextual data in compliance to the Genomic Standards Consortium specifications. The MetaBar open source code base for local installation is available under the GNU General Public License version 3 (GNU GPL3).
The MetaBar software supports the typical workflow from data acquisition and field-sampling to contextual data enriched sequence submission to an INSDC database. The integration with the megx.net marine Ecological Genomics database and portal facilitates georeferenced data integration and metadata-based comparisons of sampling sites as well as interactive data visualization. The ample export functionalities and the INSDC submission support enable exchange of data across disciplines and safeguarding contextual data.
This report summarizes the proceedings of the “Metagenomics, Metadata and Meta-analysis” (M3) Special Interest Group (SIG) meeting held at the Intelligent Systems for Molecular Biology 2009 conference. The Genomic Standards Consortium (GSC) hosted this meeting to explore the bottlenecks and emerging solutions for obtaining biological insights through large-scale comparative analysis of metagenomic datasets. The M3 SIG included 16 talks, half of which were selected from submitted abstracts, a poster session and a panel discussion involving members of the GSC Board. This report summarizes this one-day SIG, attempts to identify shared themes and recapitulates community recommendations for the future of this field. The GSC will also host an M3 workshop at the Pacific Symposium on Biocomputing (PSB) in January 2010. Further information about the GSC and its range of activities can be found at http://gensc.org/.
Megx.net is a database and portal that provides integrated access to georeferenced marker genes, environment data and marine genome and metagenome projects for microbial ecological genomics. All data are stored in the Microbial Ecological Genomics DataBase (MegDB), which is subdivided to hold both sequence and habitat data and global environmental data layers. The extended system provides access to several hundreds of genomes and metagenomes from prokaryotes and phages, as well as over a million small and large subunit ribosomal RNA sequences. With the refined Genes Mapserver, all data can be interactively visualized on a world map and statistics describing environmental parameters can be calculated. Sequence entries have been curated to comply with the proposed minimal standards for genomes and metagenomes (MIGS/MIMS) of the Genomic Standards Consortium. Access to data is facilitated by Web Services. The updated megx.net portal offers microbial ecologists greatly enhanced database content, and new features and tools for data analysis, all of which are freely accessible from our webpage http://www.megx.net.
This report summarizes the proceedings of the 6th and 7th workshops of the Genomic Standards Consortium (GSC), held back-to-back in 2008. GSC 6 focused on furthering the activities of GSC working groups, GSC 7 focused on outreach to the wider community. GSC 6 was held October 10-14, 2008 at the European Bioinformatics Institute, Cambridge, United Kingdom and included a two-day workshop focused on the refinement of the Genomic Contextual Data Markup Language (GCDML). GSC 7 was held as the opening day of the International Congress on Metagenomics 2008 in San Diego California. Major achievements of these combined meetings included an agreement from the International Nucleotide Sequence Database Consortium (INSDC) to create a “MIGS” keyword for capturing ”Minimum Information about a Genome Sequence” compliant information within INSDC (DDBJ/EMBL /Genbank) records, launch of GCDML 1.0, MIGS compliance of the first set of “Genomic Encyclopedia of Bacteria and Archaea” project genomes, approval of a proposal to extend MIGS to 16S rRNA sequences within a “Minimum Information about an Environmental Sequence”, finalization of plans for the GSC eJournal, “Standards in Genomic Sciences” (SIGS), and the formation of a GSC Board. Subsequently, the GSC has been awarded a Research Co-ordination Network (RCN4GSC) grant from the National Science Foundation, held the first SIGS workshop and launched the journal. The GSC will also be hosting outreach workshops at both ISMB 2009 and PSB 2010 focused on “Metagenomics, Metadata and MetaAnalysis” (M3). Further information about the GSC and its range of activities can be found at http://gensc.org, including videos of all the presentations at GSC 7.
Modern sequencing technologies allow rapid sequencing and bioinformatic analysis of genomes and metagenomes. With every new sequencing project a vast number of new proteins become available with many genes remaining functionally unclassified based on evidences from sequence similarities alone. Extending similarity searches with gene pattern approaches, defined as genes sharing a distinct genomic neighbourhood, have shown to significantly improve the number of functional assignments. Further functional evidences can be gained by correlating these gene patterns with prevailing environmental parameters. MetaMine was developed to approach the large pool of unclassified proteins by searching for recurrent gene patterns across habitats based on key genes.
MetaMine is an interactive data mining tool which enables the detection of gene patterns in an environmental context. The gene pattern search starts with a user defined environmentally interesting key gene. With this gene a BLAST search is carried out against the Microbial Ecological Genomics DataBase (MEGDB) containing marine genomic and metagenomic sequences. This is followed by the determination of all neighbouring genes within a given distance and a search for functionally equivalent genes. In the final step a set of common genes present in a defined number of distinct genomes is determined. The gene patterns found are associated with their individual pattern instances describing gene order and directions. They are presented together with information about the sample and the habitat. MetaMine is implemented in Java and provided as a client/server application with a user-friendly graphical user interface. The system was evaluated with environmentally relevant genes related to the methane-cycle and carbon monoxide oxidation.
MetaMine offers a targeted, semi-automatic search for gene patterns based on expert input. The graphical user interface of MetaMine provides a user-friendly overview of the computed gene patterns for further inspection in an ecological context. Prevailing biological processes associated with a key gene can be used to infer new annotations and shape hypotheses to guide further analyses. The use-cases demonstrate that meaningful gene patterns can be quickly detected using MetaMine.
MetaMine is freely available for academic use from .
With the quantity of genomic data increasing at an exponential rate, it is imperative that these data be captured electronically, in a standard format. Standardization activities must proceed within the auspices of open-access and international working bodies. To tackle the issues surrounding the development of better descriptions of genomic investigations, we have formed the Genomic Standards Consortium (GSC). Here, we introduce the minimum information about a genome sequence (MIGS) specification with the intent of promoting participation in its development and discussing the resources that will be required to develop improved mechanisms of metadata capture and exchange. As part of its wider goals, the GSC also supports improving the ‘transparency’ of the information contained in existing genomic databases.