Computational modeling of brain pathologies: the case of multiple sclerosis.

The central nervous system is the most complex network of the human body. The existence and functionality of a large number of molecular species in human brain are still ambiguous and mostly unknown, thus posing a challenge to Science and Medicine. Neurological diseases inherit the same level of complexity, making effective treatments difficult to be found. Multiple sclerosis (MS) is a major neurological disease that causes severe inabilities and also a significant social burden on health care system: between 2 and 2.5 million people are affected by it, and the cost associated with it is significantly higher as compared with other neurological diseases because of the chronic nature of the disease and to the partial efficacy of current therapies. Despite difficulties in understanding and treating MS, many computational models have been developed to help neurologists. In the present work, we briefly review the main characteristics of MS and present a selection criteria of modeling approaches.

Biggest challenges in bioinformatics.

The third Heidelberg Unseminars in Bioinformatics (HUB) was held on 18th October 2012, at Heidelberg University, Germany. HUB brought together around 40 bioinformaticians from academia and industry to discuss the 'Biggest Challenges in Bioinformatics' in a 'World Café' style event.

Agent based modeling of Treg-Teff cross regulation in relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a disease of central nervous system that causes the removal of fatty myelin sheath from axons of the brain and spinal cord. Autoimmunity plays an important role in this pathology outcome and body's own immune system attacks on the myelin sheath causing the damage. The etiology of the disease is partially understood and the response to treatment cannot easily be predicted. RESULTS: We presented the results obtained using 8 genetically predisposed randomly chosen individuals reproducing both the absence and presence of malfunctions of the Teff-Treg cross-balancing mechanisms at a local level. For simulating the absence of a local malfunction we supposed that both Teff and Treg populations had similar maximum duplication rates. Results presented here suggest that presence of a genetic predisposition is not always a sufficient condition for developing the disease. Other conditions such as a breakdown of the mechanisms that regulate and allow peripheral tolerance should be involved. CONCLUSIONS: The presented model allows to capture the essential dynamics of relapsing-remitting MS despite its simplicity. It gave useful insights that support the hypothesis of a breakdown of Teff-Treg cross balancing mechanisms.

Automatic detection of adverse events to predict drug label changes using text and data mining techniques.

PURPOSE: The aim of this study was to assess the impact of automatically detected adverse event signals from text and open-source data on the prediction of drug label changes. METHODS: Open-source adverse effect data were collected from FAERS, Yellow Cards and SIDER databases. A shallow linguistic relation extraction system (JSRE) was applied for extraction of adverse effects from MEDLINE case reports. Statistical approach was applied on the extracted datasets for signal detection and subsequent prediction of label changes issued for 29 drugs by the UK Regulatory Authority in 2009. RESULTS: 76% of drug label changes were automatically predicted. Out of these, 6% of drug label changes were detected only by text mining. JSRE enabled precise identification of four adverse drug events from MEDLINE that were undetectable otherwise. CONCLUSIONS: Changes in drug labels can be predicted automatically using data and text mining techniques. Text mining technology is mature and well-placed to support the pharmacovigilance tasks.

Semi-Automated Approach to Retrieve SNOMED CT Hierarchy of Clinical Terms by Using Terminology Server.

SNOMED CT has an enormous number of clinical concepts and mapping to SNOMED CT is considered as the foundation to achieve semantic interoperability in healthcare. Manual mapping is time-consuming and error-prone thus making this crucial step challenging. In addition, hierarchy retrieval of clinical concepts increases the challenges for the user. Terminology Servers provide an interface, which can be used to automate the process of retrieving data. In this work, it is shown that Snowstorm can significantly improve the efficiency of retrieval process if used with semi-automated workflows.

Development of a benchmark corpus to support the automatic extraction of drug-related adverse effects from medical case reports.

A significant amount of information about drug-related safety issues such as adverse effects are published in medical case reports that can only be explored by human readers due to their unstructured nature. The work presented here aims at generating a systematically annotated corpus that can support the development and validation of methods for the automatic extraction of drug-related adverse effects from medical case reports. The documents are systematically double annotated in various rounds to ensure consistent annotations. The annotated documents are finally harmonized to generate representative consensus annotations. In order to demonstrate an example use case scenario, the corpus was employed to train and validate models for the classification of informative against the non-informative sentences. A Maximum Entropy classifier trained with simple features and evaluated by 10-fold cross-validation resulted in the F1 score of 0.70 indicating a potential useful application of the corpus.

Semi-Automated Approach to Map Clinical Concepts to SNOMED CT Terms by Using Terminology Server.

SNOMED CT has an enormous number of clinical concepts and mapping to SNOMED CT is considered as the foundation to achieve semantic interoperability in healthcare. Manual mapping is time-consuming and error-prone thus making this crucial step challenging. Terminology Servers provide an interface, which can be used to automate the process of retrieving data. Snowstorm is a terminology server developed by SNOMED International. In this work, the feasibility of using Snowstorm to automate the data retrieval and mapping has been discussed.

Semi-Automated Approach to Populate any FHIR Server via POST Method.

FHIR (Fast Healthcare Interoperability Resources) is a specification for exchanging healthcare data electronically. We provide a relatively easy way to populate any FHIR server by using a workflow. A dataset of 25 FHIR JSON files with resource type Bundles, synthetically generated by using Synthea, has been tested for the population of the Vonk Server. The described approach facilitates population of any FHIR server with a KNIME workflow using POST method.

Perspectives and Obstacles for Transforming Terminologies into FHIR CodeSystems Exemplified by Alpha-ID.

The terminology services, defined as part of the emerging FHIR standard, yield a promising approach to finally achieve a common handling of coding systems needed for semantic interoperability. As a precondition, legacy terminology data must be transformed into FHIR-compatible resources whereby varying source formats make a manual case-by-case solution impracticable. In this work, the practicability of using CSIRO's Ontoserver and the related Snapper tool as support of the transformation process were evaluated by applying them to the German Alpha-ID terminology.

An OpenEHR Template with the Integrated German LOINC Terms.

An OpenEHR template based on LOINC terms in German language (LOINC-DE) has been created for the structured clinical data capture. The resulting template includes all terms available in LOINC-DE, which can be selected from the drop-down menu for clinical data capture. The template can be used as an independent laboratory form or it can be customized for local needs. This approach presents the possibility to include terminologies in EHR when capturing patient data.

Mapping of OpenEHR Archetypes to FHIR Resources in Use Case Oncology.

Unambiguous data exchange among healthcare systems is essential for error-free reporting and improved patient care. Mapping of different standards plays a crucial role in making different systems communicate with each other and have an efficient healthcare systems. This work focuses on exploring the possibilities of semantic interoperability between two widely used clinical modelling standards, OpenEHR and FHIR (Fast Healthcare Interoperability Resources). A manually curated map is being developed where the same semantically meaning OpenEHR Archetypes are mapped to the relevant FHIR Resources.

An openEHR Virtual Patient Template for Pancreatic Cancer.

openEHR is an open-source technology for e-health, aims to build data models for interoperable Electronic Health Records (EHRs) and to enhance semantic interoperability. openEHR architecture consists of different building blocks, among them is the "template" which consists of different archetypes and aims to collect the data for a specific use-case. In this paper, we created a generic data model for a virtual pancreatic cancer patient, using the openEHR approach and tools, to be used for testing and virtual environments. The data elements for this template were derived from the "Oncology minimal data set" of HiGHmed project. In addition, we generated virtual data profiles for 10 patients using the template. The objective of this exercise is to provide a data model and virtual data profiles for testing and experimenting scenarios within the openEHR environment. Both of the template and the 10 virtual patient profiles are available publicly.

Knowledge retrieval from PubMed abstracts and electronic medical records with the Multiple Sclerosis Ontology.

BACKGROUND: In order to retrieve useful information from scientific literature and electronic medical records (EMR) we developed an ontology specific for Multiple Sclerosis (MS). METHODS: The MS Ontology was created using scientific literature and expert review under the Protégé OWL environment. We developed a dictionary with semantic synonyms and translations to different languages for mining EMR. The MS Ontology was integrated with other ontologies and dictionaries (diseases/comorbidities, gene/protein, pathways, drug) into the text-mining tool SCAIView. We analyzed the EMRs from 624 patients with MS using the MS ontology dictionary in order to identify drug usage and comorbidities in MS. Testing competency questions and functional evaluation using F statistics further validated the usefulness of MS ontology. RESULTS: Validation of the lexicalized ontology by means of named entity recognition-based methods showed an adequate performance (F score = 0.73). The MS Ontology retrieved 80% of the genes associated with MS from scientific abstracts and identified additional pathways targeted by approved disease-modifying drugs (e.g. apoptosis pathways associated with mitoxantrone, rituximab and fingolimod). The analysis of the EMR from patients with MS identified current usage of disease modifying drugs and symptomatic therapy as well as comorbidities, which are in agreement with recent reports. CONCLUSION: The MS Ontology provides a semantic framework that is able to automatically extract information from both scientific literature and EMR from patients with MS, revealing new pathogenesis insights as well as new clinical information.