Towards a Semantic Data Harmonization Federated Infrastructure.

Data integration is an increasing need in medical informatics projects like the EU Precise4Q project, in which multidisciplinary semantically and syntactically heterogeneous data across several institutions needs to be integrated. Besides, data sharing agreements often allow a virtual data integration only, because data cannot leave the source repository. We propose a data harmonization infrastructure in which data is virtually integrated by sharing a semantically rich common data representation that allows their homogeneous querying. This common data model integrates content from well-known biomedical ontologies like SNOMED CT by using the BTL2 upper level ontology, and is imported into a graph database. We successfully integrated three datasets and made some test queries showing the feasibility of the approach.

Analysis of readability and structural accuracy in SNOMED CT.

BACKGROUND: The increasing adoption of ontologies in biomedical research and the growing number of ontologies available have made it necessary to assure the quality of these resources. Most of the well-established ontologies, such as the Gene Ontology or SNOMED CT, have their own quality assurance processes. These have demonstrated their usefulness for the maintenance of the resources but are unable to detect all of the modelling flaws in the ontologies. Consequently, the development of efficient and effective quality assurance methods is needed. METHODS: Here, we propose a series of quantitative metrics based on the processing of the lexical regularities existing in the content of the ontology, to analyse readability and structural accuracy. The readability metrics account for the ratio of labels, descriptions, and synonyms associated with the ontology entities. The structural accuracy metrics evaluate how two ontology modelling best practices are followed: (1) lexically suggest locally define (LSLD), that is, if what is expressed in natural language for humans is available as logical axioms for machines; and (2) systematic naming, which accounts for the amount of label content of the classes in a given taxonomy shared. RESULTS: We applied the metrics to different versions of SNOMED CT. Both readability and structural accuracy metrics remained stable in time but could capture some changes in the modelling decisions in SNOMED CT. The value of the LSLD metric increased from 0.27 to 0.31, and the value of the systematic naming metric was around 0.17. We analysed the readability and structural accuracy in the SNOMED CT July 2019 release. The results showed that the fulfilment of the structural accuracy criteria varied among the SNOMED CT hierarchies. The value of the metrics for the hierarchies was in the range of 0-0.92 (LSLD) and 0.08-1 (systematic naming). We also identified the cases that did not meet the best practices. CONCLUSIONS: We generated useful information about the engineering of the ontology, making the following contributions: (1) a set of readability metrics, (2) the use of lexical regularities to define structural accuracy metrics, and (3) the generation of quality assurance information for SNOMED CT.

Lost in translation: bioinformatic analysis of variations affecting the translation initiation codon in the human genome.

Motivation: Translation is a key biological process controlled in eukaryotes by the initiation AUG codon. Variations affecting this codon may have pathological consequences by disturbing the correct initiation of translation. Unfortunately, there is no systematic study describing these variations in the human genome. Moreover, we aimed to develop new tools for in silico prediction of the pathogenicity of gene variations affecting AUG codons, because to date, these gene defects have been wrongly classified as missense. Results: Whole-exome analysis revealed the mean of 12 gene variations per person affecting initiation codons, mostly with high (>0.01) minor allele frequency (MAF). Moreover, analysis of Ensembl data (December 2017) revealed 11 261 genetic variations affecting the initiation AUG codon of 7205 genes. Most of these variations (99.5%) have low or unknown MAF, probably reflecting deleterious consequences. Only 62 variations had high MAF. Genetic variations with high MAF had closer alternative AUG downstream codons than did those with low MAF. Besides, the high-MAF group better maintained both the signal peptide and reading frame. These differentiating elements could help to determine the pathogenicity of this kind of variation. Availability and implementation: Data and scripts in Perl and R are freely available at https://github.com/fanavarro/hemodonacion. Supplementary information: Supplementary data are available at Bioinformatics online.

Towards the semantic enrichment of Computer Interpretable Guidelines: a method for the identification of relevant ontological terms.

Clinical Practice Guidelines (CPGs) contain recommendations intended to optimize patient care, produced based on a systematic review of evidence. In turn, Computer-Interpretable Guidelines (CIGs) are formalized versions of CPGs for use as decision-support systems. We consider the enrichment of the CIG by means of an OWL ontology that describes the clinical domain of the CIG, which could be exploited e.g. for the interoperability with the Electronic Health Record (EHR). As a first step, in this paper we describe a method to support the development of such an ontology starting from a CIG. The method uses an alignment algorithm for the automated identification of ontological terms relevant to the clinical domain of the CIG, as well as a web platform to manually review the alignments and select the appropriate ones. Finally, we present the results of the application of the method to a small corpus of CIGs.