Background: Efforts to harmonize genomic data standards used by the biodiversity and metagenomic research communities have shown that prokaryotic data cannot be understood or represented in a traditional, classical biological context for conceptual reasons, not technical ones.Results: Biology, like physics, has a fundamental duality-the classical macroscale eukaryotic realm vs. the quantum microscale microbial realm-with the two realms differing profoundly, and counter-intuitively, from one another. Just as classical physics is emergent from and cannot explain the microscale realm of quantum physics, so classical biology is emergent from and cannot explain the microscale realm of prokaryotic life. Classical biology describes the familiar, macroscale realm of multi-cellular eukaryotic organisms, which constitute a highly derived and constrained evolutionary subset of the biosphere, unrepresentative of the vast, mostly unseen, microbial world of prokaryotic life that comprises at least half of the planet's biomass and most of its genetic diversity. The two realms occupy fundamentally different mega-niches: eukaryotes interact primarily mechanically with the environment, prokaryotes primarily physiologically. Further, many foundational tenets of classical biology simply do not apply to prokaryotic biology.Conclusions: Classical genetics one held that genes, arranged on chromosomes like beads on a string, were the fundamental units of mutation, recombination, and heredity. Then, molecular analysis showed that there were no fundamental units, no beads, no string. Similarly, classical biology asserts that individual organisms and species are fundamental units of ecology, evolution, and biodiversity, composing an evolutionary history of objectively real, lineage-defined groups in a single-rooted tree of life. Now, metagenomic tools are forcing a recognition that there are no completely objective individuals, no unique lineages, and no one true tree. The newly revealed biosphere of microbial dark matter cannot be understood merely by extending the concepts and methods of eukaryotic macrobiology. The unveiling of biological dark matter is allowing us to see, for the first time, the diversity of the entire biosphere and, to paraphrase Darwin, is providing a new view of life. Advancing and understanding that view will require major revisions to some of the most fundamental concepts and theories in biology.

This report summarizes the proceedings of the 14th workshop of the Genomic Standards Consortium (GSC) held at the University of Oxford in September 2012. The primary goal of the workshop was to work towards the launch of the Genomic Observatories (GOs) Network under the GSC. For the first time, it brought together potential GOs sites, GSC members, and a range of interested partner organizations. It thus represented the first meeting of the GOs Network (GOs1). Key outcomes include the formation of a core group of “champions” ready to take the GOs Network forward, as well as the formation of working groups. The workshop also served as the first meeting of a wide range of participants in the Ocean Sampling Day (OSD) initiative, a first GOs action. Three projects with complementary interests - COST Action ES1103, MG4U and Micro B3 - organized joint sessions at the workshop. A two-day GSC Hackathon followed the main three days of meetings.

The Genomic Standards Consortium (GSC) is an open-membership community that was founded in 2005 to work towards the development, implementation and harmonization of standards in the field of genomics. Starting with the defined task of establishing a minimal set of descriptions the GSC has evolved into an active standards-setting body that currently has 18 ongoing projects, with additional projects regularly proposed from within and outside the GSC. Here we describe our recently enacted policy for proposing new activities that are intended to be taken on by the GSC, along with the template for proposing such new activities.

The workshop-hackathon was convened by the Global Biodiversity Information Facility (GBIF) at its secretariat in Copenhagen over 22–24 May 2013 with additional support from several projects (RCN4GSC, EAGER, VertNet, BiSciCol, GGBN, and Micro B3). It assembled a team of experts to address the challenge of adapting the Darwin Core standard for a wide variety of sample data. Topics addressed in the workshop included 1) a review of outstanding issues in the Darwin Core standard, 2) issues relating to publishing of biodiversity data through Darwin Core Archives, 3) use of Darwin Core Archives for publishing sample and monitoring data, 4) the case for modifying the Darwin Core Text Guide specification to support many-to-many relations, and 5) the generalization of the Darwin Core Archive to a “Biodiversity Data Archive”. A wide variety of use cases were assembled and discussed in order to inform further developments.

We describe the outcomes of three recent workshops aimed at advancing development of the Biological Collections Ontology (BCO), the Population and Community Ontology (PCO), and tools to annotate data using those and other ontologies. The first workshop gathered use cases to help grow the PCO, agreed upon a format for modeling challenging concepts such as ecological niche, and developed ontology design patterns for defining collections of organisms and population-level phenotypes. The second focused on mapping datasets to ontology terms and converting them to Resource Description Framework (RDF), using the BCO. To follow-up, a BCO hackathon was held concurrently with the 16th Genomics Standards Consortium Meeting, during which we converted additional datasets to RDF, developed a Material Sample Core for the Global Biodiversity Information Framework, created a Web Ontology Language (OWL) file for importing Darwin Core classes and properties into BCO, and developed a workflow for converting biodiversity data among formats.

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.

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.

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.

This report details the outcome of the 13 th Meeting of the Genomic Standards Consortium. The three-day conference was held at the Kingkey Palace Hotel, Shenzhen, China, on March 5–7, 2012, and was hosted by the Beijing Genomics Institute. The meeting, titled From Genomes to Interactions to Communities to Models , highlighted the role of data standards associated with genomic, metagenomic, and amplicon sequence data and the contextual information associated with the sample. To this end the meeting focused on genomic projects for animals, plants, fungi, and viruses; metagenomic studies in host-microbe interactions; and the dynamics of microbial communities. In addition, the meeting hosted a Genomic Observatories Network session, a Genomic Standards Consortium biodiversity working group session, and a Microbiology of the Built Environment session sponsored by the Alfred P. Sloan Foundation.

Microbial ecology has been enhanced greatly by the ongoing 'omics revolution, bringing half the world's biomass and most of its biodiversity into analytical view for the first time; indeed, it feels almost like the invention of the microscope and the discovery of the new world at the same time. With major microbial ecology research efforts accumulating prodigious quantities of sequence, protein, and metabolite data, we are now poised to address environmental microbial research at macro scales, and to begin to characterize and understand the dimensions of microbial biodiversity on the planet. What is currently impeding progress is the need for a framework within which the research community can develop, exchange and discuss predictive ecosystem models that describe the biodiversity and functional interactions. Such a framework must encompass data and metadata transparency and interoperation; data and results validation, curation, and search; application programming interfaces for modeling and analysis tools; and human and technical processes and services necessary to ensure broad adoption. Here we discuss the need for focused community interaction to augment and deepen established community efforts, beginning with the Genomic Standards Consortium (GSC), to create a science-driven strategic plan for a Genomic Software Institute (GSI).

BACKGROUND:Data protection is important for all information systems that deal with human-subjects data. Grid-based systems--such as the cancer Biomedical Informatics Grid (caBIG)--seek to develop new mechanisms to facilitate real-time federation of cancer-relevant data sources, including sources protected under a variety of regulatory laws, such as HIPAA and 21CFR11. These systems embody new models for data sharing, and hence pose new challenges to the regulatory community, and to those who would develop or adopt them. These challenges must be understood by both systems developers and system adopters. In this paper, we describe our work collecting policy statements, expectations, and requirements from regulatory decision makers at academic cancer centers in the United States. We use these statements to examine fundamental assumptions regarding data sharing using data federations and grid computing.METHODS:An interview-based study of key stakeholders from a sample of US cancer centers. Interviews were structured, and used an instrument that was developed for the purpose of this study. The instrument included a set of problem scenarios--difficult policy situations that were derived during a full-day discussion of potentially problematic issues by a set of project participants with diverse expertise. Each problem scenario included a set of open-ended questions that were designed to elucidate stakeholder opinions and concerns. Interviews were transcribed verbatim and used for both qualitative and quantitative analysis. For quantitative analysis, data was aggregated at the individual or institutional unit of analysis, depending on the specific interview question.RESULTS:Thirty-one (31) individuals at six cancer centers were contacted to participate. Twenty-four out of thirty-one (24/31) individuals responded to our request- yielding a total response rate of 77%. Respondents included IRB directors and policy-makers, privacy and security officers, directors of offices of research, information security officers and university legal counsel. Nineteen total interviews were conducted over a period of 16 weeks. Respondents provided answers for all four scenarios (a total of 87 questions). Results were grouped by broad themes, including among others: governance, legal and financial issues, partnership agreements, de-identification, institutional technical infrastructure for security and privacy protection, training, risk management, auditing, IRB issues, and patient/subject consent.CONCLUSION:The findings suggest that with additional work, large scale federated sharing of data within a regulated environment is possible. A key challenge is developing suitable models for authentication and authorization practices within a federated environment. Authentication--the recognition and validation of a person's identity--is in fact a global property of such systems, while authorization - the permission to access data or resources--mimics data sharing agreements in being best served at a local level. Nine specific recommendations result from the work and are discussed in detail. These include: (1) the necessity to construct separate legal or corporate entities for governance of federated sharing initiatives on this scale; (2) consensus on the treatment of foreign and commercial partnerships; (3) the development of risk models and risk management processes; (4) development of technical infrastructure to support the credentialing process associated with research including human subjects; (5) exploring the feasibility of developing large-scale, federated honest broker approaches; (6) the development of suitable, federated identity provisioning processes to support federated authentication and authorization; (7) community development of requisite HIPAA and research ethics training modules by federation members; (8) the recognition of the need for central auditing requirements and authority, and; (9) use of two-protocol data exchange models where possible in the federation.

Information explosion and new advances in high throughput experiments have challenged biomedical research, and suggested a future in which inter-institutional and international collaborations will be the norm. The cancer Biomedical Informatics Grid is an ambitious initiative launched by the US National Cancer Institute to develop a network of tools, data, and researchers to support translational and clinical research in oncology, with an ultimate goal to improve cancer care for patients. The three year pilot phase of caBIG ends in 2007, and has engaged over 900 clinicians, scientists, and patient advocates as developers, adopters, and workspace participants. Progress has been demonstrated in creating tools and building prototype grid architecture for collaborative research. Accomplishments in the pilot phase set the stage for extension of the community into other biomedical domains and for federation of the caBIG enterprise with similar initiatives in other scientific areas and in other countries.

As the Human Genome Project (HGP) moves toward its successful completion, more and more people have become interested in understanding this project and its results. Since the HGP has significant ethical, legal, and social implications for all citizens, the number of individuals who do, or should wish to become familiar with the project is high. In addition to its importance in the training of professional geneticists, the HGP is of special relevance for undergraduate training in basic biology, and even for high-school and other K-12 education. Understanding the results of HGP research requires a familiarity with the notions of basic genetics. Unlike other disciplines that evolved over centuries, modern genetics began abruptly with the rediscovery of Gregor Mendel's work in 1900. Within a few years, fundamental concepts were elaborated and the foundations of genetics established. Because genetics developed so rapidly in just a few decades after 1900, the literature of that period constitutes a valuable resource even now. It may be read profitably by students and scientists wishing to understand the foundations of their field, as well as by laymen or historians of science. Unfortunately, the early literature is rapidly becoming almost inaccessible. Newer libraries do not hold older journals and even established libraries are moving their materials from that era into hard-to-reach (and impossible to browse) long-term storage in remote warehouses. To be sure, key studies from the early work are discussed in nearly all textbooks, but a comparison of these presentations with the actual literature shows that most textbook treatments have essentially mythologized the early work so that real understanding is lost. There have been several collections of classic works developed over the years (although none lately), but these suffer from the effects of the necessary, but nonetheless pernicious, highly selective sampling that accompanies these projects. Such selectivity, coupled with introductions that offer essentially modern interpretations of the work, obscure the intellectual rigor and excitement of the original efforts.

iii THE CHALLENGE 1 THE HUMAN GENOME PROJECT 2 COMPARATIVE GENOMICS: AN INTEGRATIVE BIOLOGY 5 TECHNICAL IMPEDIMENTS 6 BASIC DESIGN CHALLENGES 7 SEMANTIC CONSISTENCY 8 INTEROPERABILITY CHALLENGES 8 CONCEPTUAL IMPEDIMENTS 9 INADEQUATE DATA MODELS 11 What is a Gene? 11 What is a Map? 16 INADEQUATE SEMANTICS 16 INADEQUATE NOMENCLATURE 18 TECHNICAL ADVANCES 20 SCALABLE DATA ENTRY SYSTEMS 20 THE FEDERATION CONCEPT 21 CONCEPTUAL SOLUTIONS 22 BETTER DATA MODELS 23 THE ENZYME NOMENCLATURE SOLUTION 23 A MODEST PROPOSAL 25 AN EXAMPLE FROM TAXONOMY 27

Bioinformatics2 (the application of computers to biological information management) is part of the i r ation infrastructure that supports biological investigations. However, bioinformatics is not just another infrastructure component, no more deserving of special consideration than, say, biomicroscopy (the application of magnification to biological investigations). Instead, bioinformatics is a special case, requiring coordinated attention by members of the research community, by representatives of professional societies, and by funding agencies. With the spread of global networking, biological information resources, such as community databases, must be capable at some level of working together, of interoperating, so that users may interact with them collectively as a federated information infrastructure. In contrast, enabling infrastructure for other science, such as particle accelerators or orbiting telescopes, may operate usefully as essentially standalone facilities. Researchers interact with them, carry out work, and take the results back to their desks (or computers). This requirement of interoperability means that mere excellence as a stand-alone facility is not good enough—bioinformatics projects must also be excellent components in a larger, integrated system. This can be achieved only as a result of coordination among those who develop the systems, among the professional societies and other advisory bodies that help guide the projects, and among the agencies that support the work. The required level of coordination in maintaining these facilities is much greater than that seen in most other sponsored research or research infrastructure activities. This article presents a brief overview3 of bioinformatics activities, calling attention to those aspects that would most benefit from coordinated international attention. Issues presented are drawn more from

Information technology is transforming biology, and the relentless effects of Moore's Law are transforming that transformation. Nowhere are these changes more apparent than in the international collaboration known as the Human Genome Project (HGP). The authors consider the relationship of informatics to genomic research. Topics discussed include: the nature of information technology; Moore's Law; informatics as an enabling technology; agency commitments; community recommendations; current trends; and future support.< >