The digital revolution in phenotyping.

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.

KaBOB: ontology-based semantic integration of biomedical databases.

BACKGROUND: The ability to query many independent biological databases using a common ontology-based semantic model would facilitate deeper integration and more effective utilization of these diverse and rapidly growing resources. Despite ongoing work moving toward shared data formats and linked identifiers, significant problems persist in semantic data integration in order to establish shared identity and shared meaning across heterogeneous biomedical data sources. RESULTS: We present five processes for semantic data integration that, when applied collectively, solve seven key problems. These processes include making explicit the differences between biomedical concepts and database records, aggregating sets of identifiers denoting the same biomedical concepts across data sources, and using declaratively represented forward-chaining rules to take information that is variably represented in source databases and integrating it into a consistent biomedical representation. We demonstrate these processes and solutions by presenting KaBOB (the Knowledge Base Of Biomedicine), a knowledge base of semantically integrated data from 18 prominent biomedical databases using common representations grounded in Open Biomedical Ontologies. An instance of KaBOB with data about humans and seven major model organisms can be built using on the order of 500 million RDF triples. All source code for building KaBOB is available under an open-source license. CONCLUSIONS: KaBOB is an integrated knowledge base of biomedical data representationally based in prominent, actively maintained Open Biomedical Ontologies, thus enabling queries of the underlying data in terms of biomedical concepts (e.g., genes and gene products, interactions and processes) rather than features of source-specific data schemas or file formats. KaBOB resolves many of the issues that routinely plague biomedical researchers intending to work with data from multiple data sources and provides a platform for ongoing data integration and development and for formal reasoning over a wealth of integrated biomedical data.

Representing annotation compositionality and provenance for the Semantic Web.

BACKGROUND: Though the annotation of digital artifacts with metadata has a long history, the bulk of that work focuses on the association of single terms or concepts to single targets. As annotation efforts expand to capture more complex information, annotations will need to be able to refer to knowledge structures formally defined in terms of more atomic knowledge structures. Existing provenance efforts in the Semantic Web domain primarily focus on tracking provenance at the level of whole triples and do not provide enough detail to track how individual triple elements of annotations were derived from triple elements of other annotations. RESULTS: We present a task- and domain-independent ontological model for capturing annotations and their linkage to their denoted knowledge representations, which can be singular concepts or more complex sets of assertions. We have implemented this model as an extension of the Information Artifact Ontology in OWL and made it freely available, and we show how it can be integrated with several prominent annotation and provenance models. We present several application areas for the model, ranging from linguistic annotation of text to the annotation of disease-associations in genome sequences. CONCLUSIONS: With this model, progressively more complex annotations can be composed from other annotations, and the provenance of compositional annotations can be represented at the annotation level or at the level of individual elements of the RDF triples composing the annotations. This in turn allows for progressively richer annotations to be constructed from previous annotation efforts, the precise provenance recording of which facilitates evidence-based inference and error tracking.

The gene normalization task in BioCreative III.

BACKGROUND: We report the Gene Normalization (GN) challenge in BioCreative III where participating teams were asked to return a ranked list of identifiers of the genes detected in full-text articles. For training, 32 fully and 500 partially annotated articles were prepared. A total of 507 articles were selected as the test set. Due to the high annotation cost, it was not feasible to obtain gold-standard human annotations for all test articles. Instead, we developed an Expectation Maximization (EM) algorithm approach for choosing a small number of test articles for manual annotation that were most capable of differentiating team performance. Moreover, the same algorithm was subsequently used for inferring ground truth based solely on team submissions. We report team performance on both gold standard and inferred ground truth using a newly proposed metric called Threshold Average Precision (TAP-k). RESULTS: We received a total of 37 runs from 14 different teams for the task. When evaluated using the gold-standard annotations of the 50 articles, the highest TAP-k scores were 0.3297 (k=5), 0.3538 (k=10), and 0.3535 (k=20), respectively. Higher TAP-k scores of 0.4916 (k=5, 10, 20) were observed when evaluated using the inferred ground truth over the full test set. When combining team results using machine learning, the best composite system achieved TAP-k scores of 0.3707 (k=5), 0.4311 (k=10), and 0.4477 (k=20) on the gold standard, representing improvements of 12.4%, 21.8%, and 26.6% over the best team results, respectively. CONCLUSIONS: By using full text and being species non-specific, the GN task in BioCreative III has moved closer to a real literature curation task than similar tasks in the past and presents additional challenges for the text mining community, as revealed in the overall team results. By evaluating teams using the gold standard, we show that the EM algorithm allows team submissions to be differentiated while keeping the manual annotation effort feasible. Using the inferred ground truth we show measures of comparative performance between teams. Finally, by comparing team rankings on gold standard vs. inferred ground truth, we further demonstrate that the inferred ground truth is as effective as the gold standard for detecting good team performance.