Towards linked open gene mutations data

<p>Abstract</p> <p>Background</p> <p>With the advent of high-throughput technologies, a great wealth of variation data is being produced. Such information may constitute the basis for correlation analyses between genotypes and phenotypes and, in the future, for personalized medicine. Several databases on gene variation exist, but this kind of information is still scarce in the Semantic Web framework.</p> <p>In this paper, we discuss issues related to the integration of mutation data in the Linked Open Data infrastructure, part of the Semantic Web framework. We present the development of a mapping from the IARC TP53 Mutation database to RDF and the implementation of servers publishing this data.</p> <p>Methods</p> <p>A version of the IARC TP53 Mutation database implemented in a relational database was used as first test set. Automatic mappings to RDF were first created by using D2RQ and later manually refined by introducing concepts and properties from domain vocabularies and ontologies, as well as links to Linked Open Data implementations of various systems of biomedical interest.</p> <p>Since D2RQ query performances are lower than those that can be achieved by using an RDF archive, generated data was also loaded into a dedicated system based on tools from the Jena software suite.</p> <p>Results</p> <p>We have implemented a D2RQ Server for TP53 mutation data, providing data on a subset of the IARC database, including gene variations, somatic mutations, and bibliographic references. The server allows to browse the RDF graph by using links both between classes and to external systems. An alternative interface offers improved performances for SPARQL queries. The resulting data can be explored by using any Semantic Web browser or application.</p> <p>Conclusions</p> <p>This has been the first case of a mutation database exposed as Linked Data. A revised version of our prototype, including further concepts and IARC TP53 Mutation database data sets, is under development.</p> <p>The publication of variation information as Linked Data opens new perspectives: the exploitation of SPARQL searches on mutation data and other biological databases may support data retrieval which is presently not possible. Moreover, reasoning on integrated variation data may support discoveries towards personalized medicine.</p

DAW: Duplicate-AWare Federated Query Processing over the Web of Data

Abstract. Over the last years the Web of Data has developed into a large compendium of interlinked data sets from multiple domains. Due to the decentralised architecture of this compendium, several of these datasets contain duplicated data. Yet, so far, only little attention has been paid to the effect of duplicated data on federated querying. This work presents DAW, a novel duplicate-aware approach to feder-ated querying over the Web of Data. DAW is based on a combination of min-wise independent permutations and compact data summaries. It can be directly combined with existing federated query engines in or-der to achieve the same query recall values while querying fewer data sources. We extend three well-known federated query processing engines – DARQ, SPLENDID, and FedX – with DAW and compare our exten-sions with the original approaches. The comparison shows that DAW can greatly reduce the number of queries sent to the endpoints, while keeping high query recall values. Therefore, it can significantly improve the performance of federated query processing engines. Moreover, DAW provides a source selection mechanism that maximises the query recall, when the query processing is limited to a subset of the sources

GI Systems for public health with an ontology based approach

Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.Health is an indispensable attribute of human life. In modern age, utilizing technologies for health is one of the emergent concepts in several applied fields. Computer science, (geographic) information systems are some of the interdisciplinary fields which motivates this thesis. Inspiring idea of the study is originated from a rhetorical disease DbHd: Database Hugging Disorder, defined by Hans Rosling at World Bank Open Data speech in May 2010. The cure of this disease can be offered as linked open data, which contains ontologies for health science, diseases, genes, drugs, GEO species etc. LOD-Linked Open Data provides the systematic application of information by publishing and connecting structured data on the Web. In the context of this study we aimed to reduce boundaries between semantic web and geo web. For this reason a use case data is studied from Valencia CSISP- Research Center of Public Health in which the mortality rates for particular diseases are represented spatio-temporally. Use case data is divided into three conceptual domains (health, spatial, statistical), enhanced with semantic relations and descriptions by following Linked Data Principles. Finally in order to convey complex health-related information, we offer an infrastructure integrating geo web and semantic web. Based on the established outcome, user access methods are introduced and future researches/studies are outlined

Semantic Interpretation of User Queries for Question Answering on Interlinked Data

The Web of Data contains a wealth of knowledge belonging to a large number of domains. Retrieving data from such precious interlinked knowledge bases is an issue. By taking the structure of data into account, it is expected that upcoming generation of search engines is approaching to question answering systems, which directly answer user questions. But developing a question answering over these interlinked data sources is still challenging because of two inherent characteristics: First, different datasets employ heterogeneous schemas and each one may only contain a part of the answer for a certain question. Second, constructing a federated formal query across different datasets requires exploiting links between these datasets on both the schema and instance levels. In this respect, several challenges such as resource disambiguation, vocabulary mismatch, inference, link traversal are raised. In this dissertation, we address these challenges in order to build a question answering system for Linked Data. We present our question answering system Sina, which transforms user-supplied queries (i.e. either natural language queries or keyword queries) into conjunctive SPARQL queries over a set of interlinked data sources. The contributions of this work are as follows: 1. A novel approach for determining the most suitable resources for a user-supplied query from different datasets (disambiguation approach). We employed a Hidden Markov Model, whose parameters were bootstrapped with different distribution functions. 2. A novel method for constructing federated formal queries using the disambiguated resources and leveraging the linking structure of the underlying datasets. This approach essentially relies on a combination of domain and range inference as well as a link traversal method for constructing a connected graph, which ultimately renders a corresponding SPARQL query. 3. Regarding the problem of vocabulary mismatch, our contribution is divided into two parts, First, we introduce a number of new query expansion features based on semantic and linguistic inferencing over Linked Data. We evaluate the effectiveness of each feature individually as well as their combinations, employing Support Vector Machines and Decision Trees. Second, we propose a novel method for automatic query expansion, which employs a Hidden Markov Model to obtain the optimal tuples of derived words. 4. We provide two benchmarks for two different tasks to the community of question answering systems. The first one is used for the task of question answering on interlinked datasets (i.e. federated queries over Linked Data). The second one is used for the vocabulary mismatch task. We evaluate the accuracy of our approach using measures like mean reciprocal rank, precision, recall, and F-measure on three interlinked life-science datasets as well as DBpedia. The results of our accuracy evaluation demonstrate the effectiveness of our approach. Moreover, we study the runtime of our approach in its sequential as well as parallel implementations and draw conclusions on the scalability of our approach on Linked Data

Query Optimization Techniques For Scaling Up To Data Variety

Even though Data Lakes are efficient in terms of data storage, they increase the complexity of query processing; this can lead to expensive query execution. Hence, novel techniques for generating query execution plans are demanded. Those techniques have to be able to exploit the main characteristics of Data Lakes. Ontario is a federated query engine capable of processing queries over heterogeneous data sources. Ontario uses source descriptions based on RDF Molecule Templates, i.e., an abstract description of the properties belonging to the entities in the unified schema of the data in the Data Lake. This thesis proposes new heuristics tailored to the problem of query processing over heterogeneous data sources including heuristics specifically designed for certain data models. The proposed heuristics are integrated into the Ontario query optimizer. Ontario is compared to state-of-the-art RDF query engines in order to study the overhead introduced by considering heterogeneity during query processing. The results of the empirical evaluation suggest that there is no significant overhead when considering heterogeneity. Furthermore, the baseline version of Ontario is compared to two different sets of additional heuristics, i.e., heuristics specifically designed for certain data models and heuristics that do not consider the data model. The analysis of the obtained experimental results shows that source-specific heuristics are able to improve query performance. Ontario optimization techniques are able to generate effective and efficient query plans that can be executed over heterogeneous data sources in a Data Lake

Federated Query Processing over Heterogeneous Data Sources in a Semantic Data Lake

Data provides the basis for emerging scientific and interdisciplinary data-centric applications with the potential of improving the quality of life for citizens. Big Data plays an important role in promoting both manufacturing and scientific development through industrial digitization and emerging interdisciplinary research. Open data initiatives have encouraged the publication of Big Data by exploiting the decentralized nature of the Web, allowing for the availability of heterogeneous data generated and maintained by autonomous data providers. Consequently, the growing volume of data consumed by different applications raise the need for effective data integration approaches able to process a large volume of data that is represented in different format, schema and model, which may also include sensitive data, e.g., financial transactions, medical procedures, or personal data. Data Lakes are composed of heterogeneous data sources in their original format, that reduce the overhead of materialized data integration. Query processing over Data Lakes require the semantic description of data collected from heterogeneous data sources. A Data Lake with such semantic annotations is referred to as a Semantic Data Lake. Transforming Big Data into actionable knowledge demands novel and scalable techniques for enabling not only Big Data ingestion and curation to the Semantic Data Lake, but also for efficient large-scale semantic data integration, exploration, and discovery. Federated query processing techniques utilize source descriptions to find relevant data sources and find efficient execution plan that minimize the total execution time and maximize the completeness of answers. Existing federated query processing engines employ a coarse-grained description model where the semantics encoded in data sources are ignored. Such descriptions may lead to the erroneous selection of data sources for a query and unnecessary retrieval of data, affecting thus the performance of query processing engine. In this thesis, we address the problem of federated query processing against heterogeneous data sources in a Semantic Data Lake. First, we tackle the challenge of knowledge representation and propose a novel source description model, RDF Molecule Templates, that describe knowledge available in a Semantic Data Lake. RDF Molecule Templates (RDF-MTs) describes data sources in terms of an abstract description of entities belonging to the same semantic concept. Then, we propose a technique for data source selection and query decomposition, the MULDER approach, and query planning and optimization techniques, Ontario, that exploit the characteristics of heterogeneous data sources described using RDF-MTs and provide a uniform access to heterogeneous data sources. We then address the challenge of enforcing privacy and access control requirements imposed by data providers. We introduce a privacy-aware federated query technique, BOUNCER, able to enforce privacy and access control regulations during query processing over data sources in a Semantic Data Lake. In particular, BOUNCER exploits RDF-MTs based source descriptions in order to express privacy and access control policies as well as their automatic enforcement during source selection, query decomposition, and planning. Furthermore, BOUNCER implements query decomposition and optimization techniques able to identify query plans over data sources that not only contain the relevant entities to answer a query, but also are regulated by policies that allow for accessing these relevant entities. Finally, we tackle the problem of interest based update propagation and co-evolution of data sources. We present a novel approach for interest-based RDF update propagation that consistently maintains a full or partial replication of large datasets and deal with co-evolution

Biomedical research in a digital health framework

This article describes a Digital Health Framework (DHF), benefitting from the lessons learnt during the three-year life span of the FP7 Synergy-COPD project. The DHF aims to embrace the emerging requirements--data and tools--of applying systems medicine into healthcare with a three-tier strategy articulating formal healthcare, informal care and biomedical research. Accordingly, it has been constructed based on three key building blocks, namely, novel integrated care services with the support of information and communication technologies, a personal health folder (PHF) and a biomedical research environment (DHF-research). Details on the functional requirements and necessary components of the DHF-research are extensively presented. Finally, the specifics of the building blocks strategy for deployment of the DHF, as well as the steps toward adoption are analyzed. The proposed architectural solutions and implementation steps constitute a pivotal strategy to foster and enable 4P medicine (Predictive, Preventive, Personalized and Participatory) in practice and should provide a head start to any community and institution currently considering to implement a biomedical research platform

Protein-protein docking for interactomic studies and its aplication to personalized medicine

[eng] Proteins are the embodiment of the message encoded in the genes and they act as the building blocks and effector part of the cell. From gene regulation to cell signalling, as well as cell recognition and movement, protein-protein interactions (PPIs) drive many important cellular events by forming intricate interaction networks. The number of all non-redundant human binary interactions, forming the so-called interactome, ranges from 130,000 to 650,000 interactions as estimated by different studies. In some diseases, like cancer, these PPIs are altered by the presence of mutations in individual proteins, which can change the interaction networks of the cell resulting in a pathological state. In order to fully characterize the effect of a pathological mutation and have useful information for prediction purposes, it is important first to identify whether the mutation is located at a protein-binding interface, and second to understand the effect on the binding affinity of the affected interaction/s. To understand how these mutations can alter the PPIs, we need to look at the three-dimensional structure of the protein complexes at the atomic level. However, there are available structures for less than 10% of the estimated human interactome. Computational approaches such as protein-protein docking can help to extend the structural coverage of known PPIs. In the protein-protein docking field, rigid-body docking is a widely used docking approach, since es fast, computationally cheap and is often capable of generating a pool of models within which a near-native structure can be found. These models need to be scored in order to select the acceptable ones from the set of poses. In the present thesis, we have characterized the synergy between combination of protein-protein docking methods and several scoring functions. Our findings provide guides for the use of the most efficient scoring function for each docking method, as well as instruct future scoring functions development efforts Then we used docking calculations to predict interaction hotspots, i.e. residues that contribute the most to the binding energy, and interface patches by including neighbour residues to the predictions. We developed and validated a method, based in the Normalize Interface Propensity (NIP) score. The work of this thesis have extended the original NIP method to predict the location of disease-associated nsSNPs at protein-protein interfaces, when there is no available structure for the protein-protein complex. We have applied this approach to the pathological interaction networks of six diseases with low structural data on PPIs. This approach can almost double the number of nsSNPs that can be characterized and identify edgetic effects in many nsSNPs that were previously unknown. This methodology was also applied to predict the location of 14,551 nsSNPs in 4,254 proteins, for more than 12,000 interactions without 3D structure. We found that 34% of the disease-associated nsSNPs were located at a protein-protein interface. This opens future opportunities for the high-throughput characterization of pathological mutations at the atomic level resolution, and can help to design novel therapeutic strategies to re-stabilize the affected PPIs by disease-associated nsSNPs