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A prerequisite for systems biology is the integration and analysis of heterogeneous experimental data stored in hundreds of life-science databases and millions of scientific publications. Several standardised formats for the exchange of specific kinds of biological information exist. Such exchange languages facilitate the integration process; however they are not designed to transport integrated datasets. A format for exchanging integrated datasets needs to i) cover data from a broad range of application domains, ii) be flexible and extensible to combine many different complex data structures, iii) include metadata and semantic definitions, iv) include inferred information, v) identify the original data source for integrated entities and vi) transport large integrated datasets. Unfortunately, none of the exchange formats from the biological domain (e.g. BioPAX, MAGE-ML, PSI-MI, SBML) or the generic approaches (RDF, OWL) fulfil these requirements in a systematic way.

Interoperability among medication classification systems is known to be limited. We investigated the mapping of the Established Pharmacologic Classes (EPCs) to SNOMED CT. We compared lexical and instance-based methods to an expert-reviewed reference standard to evaluate contributions of these methods. Of the 543 EPCs, 284 had an equivalent SNOMED CT class, 205 were more specific, and 54 could not be mapped. Precision, recall, and F1 score were 0.416, 0.620, and 0.498 for lexical mapping and 0.616, 0.504, and 0.554 for instance-based mapping. Each automatic method has strengths, weaknesses, and unique contributions in mapping between medication classification systems. In our experience, it was beneficial to consider the mapping provided by both automated methods for identifying potential matches, gaps, inconsistencies, and opportunities for quality improvement between classifications. However, manual review by subject matter experts is still needed to select the most relevant mappings. [ABSTRACT FROM AUTHOR]

Phenotypes have gained increased notoriety in the clinical and biological domain owing to their application in numerous areas such as the discovery of disease genes and drug targets, phylogenetics and pharmacogenomics. Phenotypes, defined as observable characteristics of organisms, can be seen as one of the bridges that lead to a translation of experimental findings into clinical applications and thereby support 'bench to bedside' efforts. However, to build this translational bridge, a common and universal understanding of phenotypes is required that goes beyond domain-specific definitions. To achieve this ambitious goal, a digital revolution is ongoing that enables the encoding of data in computer-readable formats and the data storage in specialized repositories, ready for integration, enabling translational research. While phenome research is an ongoing endeavor, the true potential hidden in the currently available data still needs to be unlocked, offering exciting opportunities for the forthcoming years. Here, we provide insights into the state-of-the-art in digital phenotyping, by means of representing, acquiring and analyzing phenotype data. In addition, we provide visions of this field for future research work that could enable better applications of phenotype data. [ABSTRACT FROM AUTHOR]

Objective: Adverse drug events (ADEs) are undesired harmful effects resulting from use of a medication, and occur in 30% of hospitalized patients. The authors have developed a data-mining method for systematic, automated detection of ADEs from electronic medical records.Materials and Methods: This method uses the text from 9.5 million clinical notes, along with prior knowledge of drug usages and known ADEs, as inputs. These inputs are further processed into statistics used by a discriminative classifier which outputs the probability that a given drug-disorder pair represents a valid ADE association. Putative ADEs identified by the classifier are further filtered for positive support in 2 independent, complementary data sources. The authors evaluate this method by assessing support for the predictions in other curated data sources, including a manually curated, time-indexed reference standard of label change events.Results: This method uses a classifier that achieves an area under the curve of 0.94 on a held out test set. The classifier is used on 2,362,950 possible drug-disorder pairs comprised of 1602 unique drugs and 1475 unique disorders for which we had data, resulting in 240 high-confidence, well-supported drug-AE associations. Eighty-seven of them (36%) are supported in at least one of the resources that have information that was not available to the classifier.Conclusion: This method demonstrates the feasibility of systematic post-marketing surveillance for ADEs using electronic medical records, a key component of the learning healthcare system. [ABSTRACT FROM AUTHOR]

The Value Set Authority Center (VSAC) at the National Library of Medicine (NLM) provides downloadable access to all official versions of vocabulary value sets contained in the Clinical Quality Measures (CQMs) used in the certification criteria for electronic health record systems ('Meaningful Use' incentive program). Each value set consists of the numerical values (codes) and human-readable names (descriptions), drawn from standard vocabularies such as LOINC, RxNorm and SNOMED CT®, that are used to define clinical data elements used in clinical quality measures (e.g., patients with diabetes, tricyclic antidepressants). The content of the VSAC will gradually expand to incorporate value sets for other use cases, as well as for new measures and updates to existing measures. [ABSTRACT FROM AUTHOR]

Value sets (VSs) used in electronic clinical quality measures are lists of codes from standard terminologies ("extensional" VSs), whose purpose ("intension") is not always explicitly stated. We elicited the intension for the 09/01/2014 release of extensional medication value sets by comparison to drug classes from the October 2014 release of RxClass. Value sets matched drug classes if they shared common ingredients, as evidenced by Jaccard similarity score. We elicited the intension of 80 extensional value sets. The average Jaccard similarity was 0.65 for single classes and 0.80 for combination classes, with 34% (27/80) of the value sets having high similarity scores. Manual review by a pharmacist indicated 51% (41/80) of the drug classes selected as the best mapping for a value set matched the intension reflected in that value set name. This approach has the potential for facilitating the development and maintenance of medication value sets.

The Semantic Web provides a framework for the integration of resources on the web, which facilitates information integration and interoperability. RDF is the main representation format for Linked Open Data (LOD). However, datasets are not always made available in RDF by their producers and the Semantic Web community has had to convert some of these datasets to RDF in order for these datasets to participate in the LOD cloud. As a result, the LOD cloud sometimes contains outdated, partial and even inaccurate RDF datasets. We review the LOD landscape for one of these resources, MeSH, and analyze the characteristics of six existing representations in order to identify desirable features for an authoritative version, for which we create a prototype. We illustrate the suitability of this prototype on three common use cases. NLM intends to release an authoritative representation of MeSH in RDF (beta version) in the Fall of 2014.

Objective: To assess the quality of value sets in clinical quality measures, both individually and as a population of value sets., Materials and Methods: The concepts from a given value set are expected to be rooted by one or few ancestor concepts and the value set is expected to contain all the descendants of its root concepts and only these descendants. (1) We assessed the completeness and correctness of individual value sets by comparison to the extension derived from their roots. (2) We assessed the non-redundancy of value sets for the entire population of value sets (within a given code system) using the Jaccard similarity measure., Results: We demonstrated the utility of our approach on some cases of inconsistent value sets and produced a list of 58 potentially duplicate value sets from the current set of clinical quality measures for the 2014 Meaningful Use criteria., Conclusion: These metrics are easy to compute and provide compact indicators of the completeness, correctness, and non-redundancy of value sets.

Objectives: To investigate the extent to which pharmacoepidemiologic groupings are homogeneous in terms of clinical properties., Methods: In our analysis, we classified drug subgroups from the pharmacoepidemiologic Anatomical Therapeutic Chemical (ATC) classification system based on clinical drug properties. We established mappings from ATC fifth level drug entities to drug property annotations in the National Drug File Reference Terminology (NDF-RT), including therapeutic categories, mechanisms of action, and physiologic effects. Based on the annotations for the individual drugs we computed homogeneity scores for all ATC groups and analyzed their distribution., Conclusions: We found ATC groups to be generally homogeneous, more so for mechanisms of action, and physiologic effects than for therapeutic intent. However, only half of all ATC drugs can be analyzed with this approach, in part because of missing properties in NDF-RT.

Objective: To develop methods for assessing the validity, consistency and currency of value sets for clinical quality measures, in order to support the developers of quality measures in which such value sets are used., Methods: We assessed the well-formedness of the codes (in a given code system), the existence and currency of the codes in the corresponding code system, using the UMLS and RxNorm terminology services. We also investigated the overlap among value sets using the Jaccard similarity measure., Results: We extracted 163,788 codes (76,062 unique codes) from 1463 unique value sets in the 113 quality measures published by the National Quality Forum (NQF) in December 2011. Overall, 5% of the codes are invalid (4% of the unique codes). We also found 67 duplicate value sets and 10 pairs of value sets exhibiting a high degree of similarity (Jaccard > .9)., Conclusion: Invalid codes affect a large proportion of the value sets (19%). 79% of the quality Measures have at least one value set exhibiting errors. However, 50% of the quality measures exhibit errors in less than 10 % of their value sets. The existence of duplicate and highly-similar value sets suggests the need for an authoritative repository of value sets and related tooling in order to support the development of quality measures.

Membrane proteins are important for many processes in the cell and used as main drug targets. The increasing number of high-resolution structures available makes for the first time a characterization of local structural and functional motifs in alpha-helical transmembrane proteins possible. MeMotif (http://projects.biotec.tu-dresden.de/memotif) is a database and wiki which collects more than 2000 known and novel computationally predicted linear motifs in alpha-helical transmembrane proteins. Motifs are fully described in terms of several structural and functional features and editable. Motifs contained in MeMotif can be used in different biological applications, from the identification of biochemically important functional residues which are candidates for mutagenesis experiments to the improvement of tools for transmembrane protein modeling.