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.

Evaluation of ontology structural metrics based on public repository data.

The development and application of biological ontologies have increased significantly in recent years. These ontologies can be retrieved from different repositories, which do not provide much information about quality aspects of the ontologies. In the past years, some ontology structural metrics have been proposed, but their validity as measurement instrument has not been sufficiently studied to date. In this work, we evaluate a set of reproducible and objective ontology structural metrics. Given the lack of standard methods for this purpose, we have applied an evaluation method based on the stability and goodness of the classifications of ontologies produced by each metric on an ontology corpus. The evaluation has been done using ontology repositories as corpora. More concretely, we have used 119 ontologies from the OBO Foundry repository and 78 ontologies from AgroPortal. First, we study the correlations between the metrics. Second, we study whether the clusters for a given metric are stable and have a good structure. The results show that the existing correlations are not biasing the evaluation, there are no metrics generating unstable clusterings and all the metrics evaluated provide at least reasonable clustering structure. Furthermore, our work permits to review and suggest the most reliable ontology structural metrics in terms of stability and goodness of their classifications. Availability: http://sele.inf.um.es/ontology-metrics.

Gastrosquisis: presentación de caso del Hospital Escuela Universitario / Gastroschisis: Case Report from Hospital Escuela Universitario

Introducción: Gastrosquisis es una malformación congénita caracterizada por una herniación visceral a través de un defecto de la pared abdominal. Comúnmente se localiza a la derecha del cordón umbilical con protrusión visceral principalmente de íleon distal, estómago e hígado; y no se encuentra cubierto por una membrana protectora. La prevalencia de gastrosquisis es de 0.5-7 por cada 10,000 recién nacidos vivos, con un promedio de 1/2700 nacimientos a nivel mundial. La mayor prevalencia de casos con gastrosquisis ocurre en madres jóvenes <20 años y un mal estado nutricional. Descripción del caso: Madre de 18 años, primigesta, con antecedentes gineco-obstétricos de pobre cuidado prenatal. Se realizó dos ultrasonidos en hospital público durante el embarazo, los cuales no reportaron alteraciones. A las 38 semanas un día nace por cesárea, producto con diagnóstico de gastrosquisis. Tres horas después, se recibe en Hospital Escuela Universitario donde se le colocó un Silo plástico e ingresó a la unidad de cuidados inter-medios. A los 23 días de vida se hizo el cierre de la pared abdominal. Actualmente, se encuentra estable, con motilidad gastrointestinal reducida, drenaje de 50-60 mL diarios por sonda orogástrica, en ayuno y nutrición parenteral. Discusión: El reconocimiento temprano de esta patología es esencial para prevenir complicaciones mortales. Permite considerar diferentes abordajes terapéutico-quirúrgicos para alcanzar un mayor porcentaje de sobrevida, especialmente en zonas donde la incidencia es alta como en nuestro medio con una media de 17 casos anuales y una sobrevida de apenas 47%

Preliminary Analysis of the OBO Foundry Ontologies and Their Evolution Using OQuaRE.

The biomedical community has now developed a significant number of ontologies. The curation of biomedical ontologies is a complex task as they evolve rapidly, being new versions regularly published. Therefore, methods to support ontology developers in analysing and tracking the evolution of their ontologies are needed. OQuaRE is an ontology evaluation framework based on quantitative metrics that permits to obtain normalised scores for different ontologies. In this work, OQuaRE has been applied to 408 versions of the eight OBO Foundry member ontologies. The OBO Foundry member ontologies are supposed to have been built by applying the OBO Foundry principles. Our results show that this set of ontologies is actually following principles such as the naming convention, and that the evolution of the OBO Foundry member ontologies is generating ontologies with higher OQuaRE quality scores.

Supporting the analysis of ontology evolution processes through the combination of static and dynamic scaling functions in OQuaRE.

BACKGROUND: The biomedical community has now developed a significant number of ontologies. The curation of biomedical ontologies is a complex task and biomedical ontologies evolve rapidly, so new versions are regularly and frequently published in ontology repositories. This has the implication of there being a high number of ontology versions over a short time span. Given this level of activity, ontology designers need to be supported in the effective management of the evolution of biomedical ontologies as the different changes may affect the engineering and quality of the ontology. This is why there is a need for methods that contribute to the analysis of the effects of changes and evolution of ontologies. RESULTS: In this paper we approach this issue from the ontology quality perspective. In previous work we have developed an ontology evaluation framework based on quantitative metrics, called OQuaRE. Here, OQuaRE is used as a core component in a method that enables the analysis of the different versions of biomedical ontologies using the quality dimensions included in OQuaRE. Moreover, we describe and use two scales for evaluating the changes between the versions of a given ontology. The first one is the static scale used in OQuaRE and the second one is a new, dynamic scale, based on the observed values of the quality metrics of a corpus defined by all the versions of a given ontology (life-cycle). In this work we explain how OQuaRE can be adapted for understanding the evolution of ontologies. Its use has been illustrated with the ontology of bioinformatics operations, types of data, formats, and topics (EDAM). CONCLUSIONS: The two scales included in OQuaRE provide complementary information about the evolution of the ontologies. The application of the static scale, which is the original OQuaRE scale, to the versions of the EDAM ontology reveals a design based on good ontological engineering principles. The application of the dynamic scale has enabled a more detailed analysis of the evolution of the ontology, measured through differences between versions. The statistics of change based on the OQuaRE quality scores make possible to identify key versions where some changes in the engineering of the ontology triggered a change from the OQuaRE quality perspective. In the case of the EDAM, this study let us to identify that the fifth version of the ontology has the largest impact in the quality metrics of the ontology, when comparative analyses between the pairs of consecutive versions are performed.

Evaluating the Good Ontology Design Guideline (GoodOD) with the ontology quality requirements and evaluation method and metrics (OQuaRE).

OBJECTIVE: To (1) evaluate the GoodOD guideline for ontology development by applying the OQuaRE evaluation method and metrics to the ontology artefacts that were produced by students in a randomized controlled trial, and (2) informally compare the OQuaRE evaluation method with gold standard and competency questions based evaluation methods, respectively. BACKGROUND: In the last decades many methods for ontology construction and ontology evaluation have been proposed. However, none of them has become a standard and there is no empirical evidence of comparative evaluation of such methods. This paper brings together GoodOD and OQuaRE. GoodOD is a guideline for developing robust ontologies. It was previously evaluated in a randomized controlled trial employing metrics based on gold standard ontologies and competency questions as outcome parameters. OQuaRE is a method for ontology quality evaluation which adapts the SQuaRE standard for software product quality to ontologies and has been successfully used for evaluating the quality of ontologies. METHODS: In this paper, we evaluate the effect of training in ontology construction based on the GoodOD guideline within the OQuaRE quality evaluation framework and compare the results with those obtained for the previous studies based on the same data. RESULTS: Our results show a significant effect of the GoodOD training over developed ontologies by topics: (a) a highly significant effect was detected in three topics from the analysis of the ontologies of untrained and trained students; (b) both positive and negative training effects with respect to the gold standard were found for five topics. CONCLUSION: The GoodOD guideline had a significant effect over the quality of the ontologies developed. Our results show that GoodOD ontologies can be effectively evaluated using OQuaRE and that OQuaRE is able to provide additional useful information about the quality of the GoodOD ontologies.

Cell growth and cell division in the rod-shaped actinomycete Corynebacterium glutamicum.

Bacterial cell growth and cell division are highly complicated and diversified biological processes. In most rod-shaped bacteria, actin-like MreB homologues produce helicoidal structures along the cell that support elongation of the lateral cell wall. An exception to this rule is peptidoglycan synthesis in the rod-shaped actinomycete Corynebacterium glutamicum, which is MreB-independent. Instead, during cell elongation this bacterium synthesizes new cell-wall material at the cell poles whereas the lateral wall remains inert. Thus, the strategy employed by C. glutamicum to acquire a rod-shaped morphology is completely different from that of Escherichia coli or Bacillus subtilis. Cell division in C. glutamicum also differs profoundly by the apparent absence in its genome of homologues of spatial or temporal regulators of cell division, and its cell division apparatus seems to be simpler than those of other bacteria. Here we review recent advances in our knowledge of the C. glutamicum cell cycle in order to further understand this very different model of rod-shape acquisition.

Recombinant production of Streptococcus equisimilis streptokinase by Streptomyces lividans.

BACKGROUND: Streptokinase (SK) is a potent plasminogen activator with widespread clinical use as a thrombolytic agent. It is naturally secreted by several strains of beta-haemolytic streptococci. The low yields obtained in SK production, lack of developed gene transfer methodology and the pathogenesis of its natural host have been the principal reasons to search for a recombinant source for this important therapeutic protein. We report here the expression and secretion of SK by the Gram-positive bacterium Streptomyces lividans. The structural gene encoding SK was fused to the Streptomyces venezuelae CBS762.70 subtilisin inhibitor (vsi) signal sequence or to the Streptomyces lividans xylanase C (xlnC) signal sequence. The native Vsi protein is translocated via the Sec pathway while the native XlnC protein uses the twin-arginine translocation (Tat) pathway. RESULTS: SK yield in the spent culture medium of S. lividans was higher when the Sec-dependent signal peptide mediates the SK translocation. Using a 1.5 L fermentor, the secretory production of the Vsi-SK fusion protein reached up to 15 mg SK/l. SK was partially purified from the culture supernatant by DEAE-Sephacel chromatography. A 44-kDa degradation product co-eluted with the 47-kDa mature SK. The first amino acid residues of the S. lividans-produced SK were identical with those of the expected N-terminal sequence. The Vsi signal peptide was thus correctly cleaved off and the N-terminus of mature Vsi-SK fusion protein released by S. lividans remained intact. This result also implicates that the processing of the recombinant SK secreted by Streptomyces probably occurred at its C-terminal end, as in its native host Streptococcus equisimilis. The specific activity of the partially purified Streptomyces-derived SK was determined at 2661 IU/mg protein. CONCLUSION: Heterologous expression of Streptococcus equisimilis ATCC9542 skc-2 in Streptomyces lividans was successfully achieved. SK can be translocated via both the Sec and the Tat pathway in S. lividans, but yield was about 30 times higher when the SK was fused to the Sec-dependent Vsi signal peptide compared to the fusion with the Tat-dependent signal peptide of S. lividans xylanase C. Small-scale fermentation led to a fourfold improvement of secretory SK yield in S. lividans compared to lab-scale conditions. The partially purified SK showed biological activity. Streptomyces lividans was shown to be a valuable host for the production of a world-wide important, biopharmaceutical product in a bio-active form.

Streptomyces as host for recombinant production of Mycobacterium tuberculosis proteins.

The 45/47 kDa APA protein (Rv1860) of Mycobacterium tuberculosis was produced by Streptomyces lividans. The recombinant protein could be recovered from the culture medium of an S. lividans clone containing the apa gene under control of the promoter and signal sequence of the Streptomyces coelicolor agarase gene. The recombinant protein production was further scaled-up using fermentation conditions. The APA protein was subsequently purified from the culture supernatant by means of immunochromatography. About 80 mg of recombinant protein were obtained per liter of culture media. In vivo tests with the APA protein purified from S. lividans TK24/pRGAPA1 revealed that the recombinant protein was antigenic and could induce high titers of specific antibodies in the mouse biological model. Results obtained concerning heterologous production of APA, its immunogenic and antigenic capacity, demonstrated the potential of S. lividans as a valuable host for the production of recombinant proteins from M. tuberculosis.