Efficiency of Machine Learning Algorithms for the Determination of Macrovesicular Steatosis in Frozen Sections Stained with Sudan to Evaluate the Quality of the Graft in Liver Transplantation.

Liver transplantation is the only curative treatment option in patients diagnosed with end-stage liver disease. The low availability of organs demands an accurate selection procedure based on histological analysis, in order to evaluate the allograft. This assessment, traditionally carried out by a pathologist, is not exempt from subjectivity. In this sense, new tools based on machine learning and artificial vision are continuously being developed for the analysis of medical images of different typologies. Accordingly, in this work, we develop a computer vision-based application for the fast and automatic objective quantification of macrovesicular steatosis in histopathological liver section slides stained with Sudan stain. For this purpose, digital microscopy images were used to obtain thousands of feature vectors based on the RGB and CIE L*a*b* pixel values. These vectors, under a supervised process, were labelled as fat vacuole or non-fat vacuole, and a set of classifiers based on different algorithms were trained, accordingly. The results obtained showed an overall high accuracy for all classifiers (>0.99) with a sensitivity between 0.844 and 1, together with a specificity >0.99. In relation to their speed when classifying images, KNN and Naïve Bayes were substantially faster than other classification algorithms. Sudan stain is a convenient technique for evaluating ME in pre-transplant liver biopsies, providing reliable contrast and facilitating fast and accurate quantification through the machine learning algorithms tested.

CLIN-IK-LINKS: A platform for the design and execution of clinical data transformation and reasoning workflows.

BACKGROUND AND OBJECTIVE: Effective sharing and reuse of Electronic Health Records (EHR) requires technological solutions which deal with different representations and different models of data. This includes information models, domain models and, ideally, inference models, which enable clinical decision support based on a knowledge base and facts. Our goal is to develop a framework to support EHR interoperability based on transformation and reasoning services intended for clinical data and knowledge. METHODS: Our framework is based on workflows whose primary components are reusable mappings. Key features are an integrated representation, storage, and exploitation of different types of mappings for clinical data transformation purposes, as well as the support for the discovery of new workflows. The current framework supports mappings which take advantage of the best features of EHR standards and ontologies. Our proposal is based on our previous results and experience working with both technological infrastructures. RESULTS: We have implemented CLIN-IK-LINKS, a web-based platform that enables users to create, modify and delete mappings as well as to define and execute workflows. The platform has been applied in two use cases: semantic publishing of clinical laboratory test results; and implementation of two colorectal cancer screening protocols. Real data have been used in both use cases. CONCLUSIONS: The CLIN-IK-LINKS platform allows the composition and execution of clinical data transformation workflows to convert EHR data into EHR and/or semantic web standards. Having proved its usefulness to implement clinical data transformation applications of interest, CLIN-IK-LINKS can be regarded as a valuable contribution to improve the semantic interoperability of EHR systems.

ColPortal, an integrative multiomic platform for analysing epigenetic interactions in colorectal cancer.

Colorectal cancer (CRC) is the third leading cause of cancer mortality worldwide. Different pathological pathways and molecular drivers have been described and some of the associated markers are used to select effective anti-neoplastic therapy. More recent evidence points to a causal role of microbiota and altered microRNA expression in CRC carcinogenesis, but their relationship with pathological drivers or molecular phenotypes is not clearly established. Joint analysis of clinical and omics data can help clarify such relations. We present ColPortal, a platform that integrates transcriptomic, microtranscriptomic, methylomic and microbiota data of patients with colorectal cancer. ColPortal also includes detailed information of histological features and digital histological slides from the study cases, since histology is a morphological manifestation of a complex molecular change. The current cohort consists of Caucasian patients from Europe. For each patient, demographic information, location, histology, tumor staging, tissue prognostic factors, molecular biomarker status and clinical outcomes are integrated with omics data. ColPortal allows one to perform multiomics analyses for groups of patients selected by their clinical data.

Combining Archetypes, Ontologies and Formalization Enables Automated Computation of Quality Indicators.

ArchMS is a framework that represents clinical information and knowledge using ontologies in OWL, which facilitates semantic interoperability and thereby the exploitation and secondary use of clinical data. However, it does not yet support the automated assessment of quality of care. CLIF is a stepwise method to formalize quality indicators. The method has been implemented in the CLIF tool which supports its users in generating computable queries based on a patient data model which can be based on archetypes. To enable the automated computation of quality indicators using ontologies and archetypes, we tested whether ArchMS and the CLIF tool can be integrated. We successfully automated the process of generating SPARQL queries from quality indicators that have been formalized with CLIF and integrated them into ArchMS. Hence, ontologies and archetypes can be combined for the execution of formalized quality indicators.

The Orthology Ontology: development and applications.

BACKGROUND: Computational comparative analysis of multiple genomes provides valuable opportunities to biomedical research. In particular, orthology analysis can play a central role in comparative genomics; it guides establishing evolutionary relations among genes of organisms and allows functional inference of gene products. However, the wide variations in current orthology databases necessitate the research toward the shareability of the content that is generated by different tools and stored in different structures. Exchanging the content with other research communities requires making the meaning of the content explicit. DESCRIPTION: The need for a common ontology has led to the creation of the Orthology Ontology (ORTH) following the best practices in ontology construction. Here, we describe our model and major entities of the ontology that is implemented in the Web Ontology Language (OWL), followed by the assessment of the quality of the ontology and the application of the ORTH to existing orthology datasets. This shareable ontology enables the possibility to develop Linked Orthology Datasets and a meta-predictor of orthology through standardization for the representation of orthology databases. The ORTH is freely available in OWL format to all users at http://purl.org/net/orth . CONCLUSIONS: The Orthology Ontology can serve as a framework for the semantic standardization of orthology content and it will contribute to a better exploitation of orthology resources in biomedical research. The results demonstrate the feasibility of developing shareable datasets using this ontology. Further applications will maximize the usefulness of this ontology.

A platform for exploration into chaining of web services for clinical data transformation and reasoning.

The heterogeneity of clinical data is a key problem in the sharing and reuse of Electronic Health Record (EHR) data. We approach this problem through the combined use of EHR standards and semantic web technologies, concretely by means of clinical data transformation applications that convert EHR data in proprietary format, first into clinical information models based on archetypes, and then into RDF/OWL extracts which can be used for automated reasoning. In this paper we describe a proof-of-concept platform to facilitate the (re)configuration of such clinical data transformation applications. The platform is built upon a number of web services dealing with transformations at different levels (such as normalization or abstraction), and relies on a collection of reusable mappings designed to solve specific transformation steps in a particular clinical domain. The platform has been used in the development of two different data transformation applications in the area of colorectal cancer.

Lessons learned in the generation of biomedical research datasets using Semantic Open Data technologies.

Biomedical research usually requires combining large volumes of data from multiple heterogeneous sources. Such heterogeneity makes difficult not only the generation of research-oriented dataset but also its exploitation. In recent years, the Open Data paradigm has proposed new ways for making data available in ways that sharing and integration are facilitated. Open Data approaches may pursue the generation of content readable only by humans and by both humans and machines, which are the ones of interest in our work. The Semantic Web provides a natural technological space for data integration and exploitation and offers a range of technologies for generating not only Open Datasets but also Linked Datasets, that is, open datasets linked to other open datasets. According to the Berners-Lee's classification, each open dataset can be given a rating between one and five stars attending to can be given to each dataset. In the last years, we have developed and applied our SWIT tool, which automates the generation of semantic datasets from heterogeneous data sources. SWIT produces four stars datasets, given that fifth one can be obtained by being the dataset linked from external ones. In this paper, we describe how we have applied the tool in two projects related to health care records and orthology data, as well as the major lessons learned from such efforts.

Transformation of standardized clinical models based on OWL technologies: from CEM to OpenEHR archetypes.

INTRODUCTION: The semantic interoperability of electronic healthcare records (EHRs) systems is a major challenge in the medical informatics area. International initiatives pursue the use of semantically interoperable clinical models, and ontologies have frequently been used in semantic interoperability efforts. The objective of this paper is to propose a generic, ontology-based, flexible approach for supporting the automatic transformation of clinical models, which is illustrated for the transformation of Clinical Element Models (CEMs) into openEHR archetypes. METHODS: Our transformation method exploits the fact that the information models of the most relevant EHR specifications are available in the Web Ontology Language (OWL). The transformation approach is based on defining mappings between those ontological structures. We propose a way in which CEM entities can be transformed into openEHR by using transformation templates and OWL as common representation formalism. The transformation architecture exploits the reasoning and inferencing capabilities of OWL technologies. RESULTS: We have devised a generic, flexible approach for the transformation of clinical models, implemented for the unidirectional transformation from CEM to openEHR, a series of reusable transformation templates, a proof-of-concept implementation, and a set of openEHR archetypes that validate the methodological approach. CONCLUSIONS: We have been able to transform CEM into archetypes in an automatic, flexible, reusable transformation approach that could be extended to other clinical model specifications. We exploit the potential of OWL technologies for supporting the transformation process. We believe that our approach could be useful for international efforts in the area of semantic interoperability of EHR systems.

Ontology patterns-based transformation of clinical information.

The semantic interoperability of clinical information requires methods able to transform heterogeneous data sources from both technological and structural perspectives, into representations that facilitate the sharing of meaning. The SemanticHealthNet (SHN) project proposes using semantic content patterns for representing clinical information based on a model of meaning, preventing users from a deep knowledge on ontology and description logics formalism. In this work we propose a flexible transformation method that uses semantic content patterns to guide the mapping between the source data and a target domain ontology. As use case we show how one of the semantic content patterns proposed in SHN can be used to transform heterogeneous data about medication administration.

Leveraging electronic healthcare record standards and semantic web technologies for the identification of patient cohorts.

BACKGROUND: The secondary use of electronic healthcare records (EHRs) often requires the identification of patient cohorts. In this context, an important problem is the heterogeneity of clinical data sources, which can be overcome with the combined use of standardized information models, virtual health records, and semantic technologies, since each of them contributes to solving aspects related to the semantic interoperability of EHR data. OBJECTIVE: To develop methods allowing for a direct use of EHR data for the identification of patient cohorts leveraging current EHR standards and semantic web technologies. MATERIALS AND METHODS: We propose to take advantage of the best features of working with EHR standards and ontologies. Our proposal is based on our previous results and experience working with both technological infrastructures. Our main principle is to perform each activity at the abstraction level with the most appropriate technology available. This means that part of the processing will be performed using archetypes (ie, data level) and the rest using ontologies (ie, knowledge level). Our approach will start working with EHR data in proprietary format, which will be first normalized and elaborated using EHR standards and then transformed into a semantic representation, which will be exploited by automated reasoning. RESULTS: We have applied our approach to protocols for colorectal cancer screening. The results comprise the archetypes, ontologies, and datasets developed for the standardization and semantic analysis of EHR data. Anonymized real data have been used and the patients have been successfully classified by the risk of developing colorectal cancer. CONCLUSIONS: This work provides new insights in how archetypes and ontologies can be effectively combined for EHR-driven phenotyping. The methodological approach can be applied to other problems provided that suitable archetypes, ontologies, and classification rules can be designed.

Linking genome annotation projects with genetic disorders using ontologies.

Genome sequencing projects generate vast amounts of data of a wide variety of types and complexities, and at a growing pace. Traditionally, the annotation of such sequences was difficult to share with other researchers. Despite the fact that this has improved with the development and application of biological ontologies, such annotation efforts remain isolated since the amount of information that can be used from other annotation projects is limited. In addition to this, they do not benefit from the translational information available for the genomic sequences. In this paper, we describe a system that supports genome annotation processes by providing useful information about orthologous genes and the genetic disorders which can be associated with a gene identified in a sequence. The seamless integration of such data will be facilitated by an ontological infrastructure which, following best practices in ontology engineering, will reuse existing biological ontologies like Sequence Ontology or Ontological Gene Orthology.

Recommendation of standardized health learning contents using archetypes and semantic web technologies.

Linking Electronic Healthcare Records (EHR) content to educational materials has been considered a key international recommendation to enable clinical engagement and to promote patient safety. This would suggest citizens to access reliable information available on the web and to guide them properly. In this paper, we describe an approach in that direction, based on the use of dual model EHR standards and standardized educational contents. The recommendation method will be based on the semantic coverage of the learning content repository for a particular archetype, which will be calculated by applying semantic web technologies like ontologies and semantic annotations.