Advances in biodiversity: metagenomics and the unveiling of biological dark matter.

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.

RCN4GSC Workshop Report: Modeling a Testbed for Managing Data at the Interface of Biodiversity and (Meta)Genomics, April 2011.

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.

RCN4GSC Workshop Report: Managing Data at the Interface of Biodiversity and (Meta)Genomics, March 2011.

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.

RCN4GSC Meeting Report: Initiating a Testbed for Managing Data at the Interface of Biodiversity and Genomics/Metagenomics, May 2011.

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.

Security and privacy requirements for a multi-institutional cancer research data grid: an interview-based study.

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.