Enriching the Human Phenotype Ontology with inferred axioms from textual descriptions

The Human Phenotype Ontology (HP) is a reference vocabulary of human phenotypic abnormalities. HP, apart from the textual information (general definitions, descriptions, synonyms, etc.) of each ontology concept, also provides computer-readable logical definitions (axioms) of terms that will allow human phenotypic abnormalities to be related to entities from anatomy, pathology, biochemistry and other areas. In this paper we present a prototype to generate new axiomatic knowledge from the textual descriptions of each HP term. The prototype (i) detects terms in the textual descriptions and not found in the given logical expressions, (ii) generates pair combinations of those terms, (iii) builds triples after detecting the most probable relation between the pair of terms using a statistical model and, finally, (iv) suggests the most probable triples to the user so she can decide which ones can be added to the original axioms

Exploring and linking biomedical resources through multidimensional semantic spaces

Background The semantic integration of biomedical resources is still a challenging issue which is required for effective information processing and data analysis. The availability of comprehensive knowledge resources such as biomedical ontologies and integrated thesauri greatly facilitates this integration effort by means of semantic annotation, which allows disparate data formats and contents to be expressed under a common semantic space. In this paper, we propose a multidimensional representation for such a semantic space, where dimensions regard the different perspectives in biomedical research (e.g., population, disease, anatomy and protein/genes). Results This paper presents a novel method for building multidimensional semantic spaces from semantically annotated biomedical data collections. This method consists of two main processes: knowledge and data normalization. The former one arranges the concepts provided by a reference knowledge resource (e.g., biomedical ontologies and thesauri) into a set of hierarchical dimensions for analysis purposes. The latter one reduces the annotation set associated to each collection item into a set of points of the multidimensional space. Additionally, we have developed a visual tool, called 3D-Browser, which implements OLAP-like operators over the generated multidimensional space. The method and the tool have been tested and evaluated in the context of the Health-e-Child (HeC) project. Automatic semantic annotation was applied to tag three collections of abstracts taken from PubMed, one for each target disease of the project, the Uniprot database, and the HeC patient record database. We adopted the UMLS Meta-thesaurus 2010AA as the reference knowledge resource. Conclusions Current knowledge resources and semantic-aware technology make possible the integration of biomedical resources. Such an integration is performed through semantic annotation of the intended biomedical data resources. This paper shows how these annotations can be exploited for integration, exploration, and analysis tasks. Results over a real scenario demonstrate the viability and usefulness of the approach, as well as the quality of the generated multidimensional semantic spaces

Building conceptual spaces for exploring and linking biomedical resources

The establishment of links between data (e.g., patient records) and Web resources (e.g., literature) and the proper visualization of such discovered knowledge is still a challenge in most Life Science domains (e.g., biomedicine). In this paper we present our contribution to the community in the form of an infrastructure to annotate information resources, to discover relationships among them, and to represent and visualize the new discovered knowledge. Furthermore, we have also implemented a Web-based prototype tool which integrates the proposed infrastructure

Aplicación de nuevas técnicas docentes en la asignatura Sistemas Cliente/Servidor

En este trabajo mostramos nuestras experiencias en la aplicación de metodologías de aprendizaje cooperativo y basado en proyectos en la asignatura Sistemas Cliente/Servidor en los cursos académicos 2008/2009 y 2009/2010.SUMMARY: In this work we present our teaching experience in the aplication of cooperative and project-based learning methodologies within the subject Client/Server Systems in the academic years 2008/2009 and 2009/2010.Peer Reviewe

Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies

Background Although neutrophils have been linked to the progression of cancer, uncertainty exists around their association with cancer outcomes, depending on the site, outcome and treatments considered. We aimed to evaluate the strength and validity of evidence on the association between either the neutrophil to lymphocyte ratio (NLR) or tumour-associated neutrophils (TAN) and cancer prognosis. Methods We searched MEDLINE, Embase and Cochrane Database of Systematic Reviews from inception to 29 May 2020 for systematic reviews and meta-analyses of observational studies on neutrophil counts (here NLR or TAN) and specific cancer outcomes related to disease progression or survival. The available evidence was graded as strong, highly suggestive, suggestive, weak or uncertain through the application of pre-set GRADE criteria. Results A total of 204 meta-analyses from 86 studies investigating the association between either NLR or TAN and cancer outcomes met the criteria for inclusion. All but one meta-analyses found a hazard ratio (HR) which increased risk (HR > 1). We did not find sufficient meta-analyses to evaluate TAN and cancer outcomes (N = 9). When assessed for magnitude of effect, significance and bias related to heterogeneity and small study effects, 18 (9%) associations between NLR and outcomes in composite cancer endpoints (combined analysis), cancers treated with immunotherapy and some site specific cancers (urinary, nasopharyngeal, gastric, breast, endometrial, soft tissue sarcoma and hepatocellular cancers) were supported by strong evidence. Conclusion In total, 60 (29%) meta-analyses presented strong or highly suggestive evidence. Although the NLR and TAN hold clinical promise in their association with poor cancer prognosis, further research is required to provide robust evidence, assess causality and test clinical utility

First steps in the logic-based assessment of post-composed phenotypic descriptions

In this paper we present a preliminary logic-based evaluation of the integration of post-composed phenotypic descriptions with domain ontologies. The evaluation has been performed using a description logic reasoner together with scalable techniques: ontology modularization and approximations of the logical difference between ontologies

Phylogenetic diversity and temporal variation in the Spirochaeta populations from two Mediterranean microbial mats

Spirochetes represent one of the bacterial groups often observed in hydrogen- sulfide-rich layers from coastal microbial mats. However, relatively few spirochetes from these microbial mats have been described and characterized. We have used 16S rDNA phylogenetic analysis to investigate the spirochetal diversity of microbial mats from two different geographic locations in the western Mediterranean (Ebro Delta, Spain, and Camargue, France). Samples from each delta was monitored in the spring and winter over 1 to 2 year’s duration. In the sequence analysis of 332 clones derived from samples of both deltas, 42 novel phylotypes of not-yet-cultivated spirochetes belonging to the genus Spirochaeta were detected. None of the phylotypes were identified as known culturable species of Spirochaeta or previously identified phylotyepes cloned from other hypersaline microbial mat such as Guerrero Negro. Eight of the phylotypes were common to Ebro and Camargue mats, two of them, IF058 and LL066 are present both in spring and winter. Some phylotypes appeared to show seasonal variation, i.e. they were found only in the spring, but not in the winter. On the other hand, Ebro and Camargue phylotypes compared with phylotypes from Guerrero Negro grouped according to the vertical gradient of oxygen and sulfide in the mat. Some phylotypes, such as LH073, IE028, LH042 or LG013 are harbored in low H2S or H2S-O2 interface zone. In contrast, major phylotypes were detected presumably in deeper layers and they are likely to be strict anaerobes and high tolerance to H2S. The presence of spirochetes in different located microbial mats suggests that constitutes a very diverse and stable population involved in a well-integrated “symbiosis” (i.e., permanent physiological cooperation) with other guild-populations in the mats to maintain a coordinated functional and stable community

Heterogeneity in Multiple Sclerosis: Scratching the Surface of a Complex Disease

Multiple Sclerosis (MS) is the most common demyelinating disease of the central nervous system. Although the etiology and the pathogenesis of MS has been extensively investigated, no single pathway, reliable biomarker, diagnostic test, or specific treatment have yet been identified for all MS patients. One of the reasons behind this failure is likely to be the wide heterogeneity observed within the MS population. The clinical course of MS is highly variable and includes several subcategories and variants. Moreover, apart from the well-established association with the HLA-class II DRB1*15:01 allele, other genetic variants have been shown to vary significantly across different populations and individuals. Finally both pathological and immunological studies suggest that different pathways may be active in different MS patients. We conclude that these “MS subtypes” should still be considered as part of the same disease but hypothesize that spatiotemporal effects of genetic and environmental agents differentially influence MS course. These considerations are extremely relevant, as outcome prediction and personalised medicine represent the central aim of modern research

The Effect of Single Nucleotide Polymorphisms from Genome Wide Association Studies in Multiple Sclerosis on Gene Expression

BACKGROUND: Multiple sclerosis (MS) is a complex neurological disorder. Its aetiology involves both environmental and genetic factors. Recent genome-wide association studies have identified a number of single nucleotide polymorphisms (SNPs) associated with susceptibility to (MS). We investigated whether these genetic variations were associated with alteration in gene expression. METHODS/PRINCIPAL FINDINGS: We used a database of mRNA expression and genetic variation derived from immortalised peripheral lymphocytes to investigate polymorphisms associated with MS for correlation with gene expression. Several SNPs were found to be associated with changes in expression: in particular two with HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRB1, HLA-DRB4 and HLA-DRB5, one with ZFP57, one with CD58, two with IL7 and FAM164A, and one with FAM119B, TSFM and KUB3. We found minimal cross-over with a recent whole genome expression study in MS patients. DISCUSSION: We have shown that many susceptibility loci in MS are associated with changes in gene expression using an unbiased expression database. Several of these findings suggest novel gene candidates underlying the effects of MS-associated genetic variation

Reuse of terminological resources for efficient ontological engineering in Life Sciences

This paper is intended to explore how to use terminological resources for ontology engineering. Nowadays there are several biomedical ontologies describing overlapping domains, but there is not a clear correspondence between the concepts that are supposed to be equivalent or just similar. These resources are quite precious but their integration and further development are expensive. Terminologies may support the ontological development in several stages of the lifecycle of the ontology; e.g. ontology integration. In this paper we investigate the use of terminological resources during the ontology lifecycle. We claim that the proper creation and use of a shared thesaurus is a cornerstone for the successful application of the Semantic Web technology within life sciences. Moreover, we have applied our approach to a real scenario, the Health-e-Child (HeC) project, and we have evaluated the impact of filtering and re-organizing several resources. As a result, we have created a reference thesaurus for this project, named HeCTh