A Life Cycle Approach to the Development and Validation of an Ontology of the U.S. Common Rule (45 C.F.R. § 46)

Requirements for the protection of human research subjects stem from directly from federal regulation by the Department of Health and Human Services in Title 45 of the Code of Federal Regulations (C.F.R.) part 46. 15 other federal agencies include subpart A of part 46 verbatim in their own body of regulation. Hence 45 C.F.R. part 46 subpart A has come to be called colloquially the ‘Common Rule.’ Overall motivation for this study began as a desire to facilitate the ethical sharing of biospecimen samples from large biospecimen collections by using ontologies. Previous work demonstrated that in general the informed consent process and subsequent decision making about data and specimen release still relies heavily on paper-based informed consent forms and processes. Consequently, well-validated computable models are needed to provide an enhanced foundation for data sharing. This dissertation describes the development and validation of a Common Rule Ontology (CRO), expressed in the OWL-2 Web Ontology Language, and is intended to provide a computable semantic knowledge model for assessing and representing components of the information artifacts of required as part of regulated research under 45 C.F.R. § 46. I examine if the alignment of this ontology with the Basic Formal Ontology and other ontologies from the Open Biomedical Ontology (OBO) Foundry provide a good fit for the regulatory aspects of the Common Rule Ontology. The dissertation also examines and proposes a new method for ongoing evaluation of ontology such as CRO across the ontology development lifecycle and suggest methods to achieve high quality, validated ontologies. While the CRO is not in itself intended to be a complete solution to the data and specimen sharing problems outlined above, it is intended to produce a well-validated computationally grounded framework upon which others can build. This model can be used in future work to build decision support systems to assist Institutional Review Boards (IRBs), regulatory personnel, honest brokers, tissue bank managers, and other individuals in the decision-making process involving biorepository specimen and data sharing

Metabolite profiling reveals new insights into the regulation of serum urate in humans

Albrecht E, Waldenberger M, Krumsiek J, et al. Metabolite profiling reveals new insights into the regulation of serum urate in humans. Metabolomics. 2013;10(1):141-151.Serum urate, the final breakdown product of purine metabolism, is causally involved in the pathogenesis of gout, and implicated in cardiovascular disease and type 2 diabetes. Serum urate levels highly differ between men and women; however the underlying biological processes in its regulation are still not completely understood and are assumed to result from a complex interplay between genetic, environmental and lifestyle factors. In order to describe the metabolic vicinity of serum urate, we analyzed 355 metabolites in 1,764 individuals of the population-based KORA F4 study and constructed a metabolite network around serum urate using Gaussian Graphical Modeling in a hypothesis-free approach. We subsequently investigated the effect of sex and urate lowering medication on all 38 metabolites assigned to the network. Within the resulting network three main clusters could be detected around urate, including the well-known pathway of purine metabolism, as well as several dipeptides, a group of essential amino acids, and a group of steroids. Of the 38 assigned metabolites, 25 showed strong differences between sexes. Association with uricostatic medication intake was not only confined to purine metabolism but seen for seven metabolites within the network. Our findings highlight pathways that are important in the regulation of serum urate and suggest that dipeptides, amino acids, and steroid hormones are playing a role in its regulation. The findings might have an impact on the development of specific targets in the treatment and prevention of hyperuricemia

Bostonia: The Boston University Alumni Magazine. Volume 15

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs