Answers to the most complex biological questions are rarely determined solely from the experimental evidence. It requires subsequent analysis of many data sources that are often heterogeneous. Most biological data repositories focus on providing only one particular type of data, such as sequences, molecular interactions, protein structure, or gene expression. In many cases, it is required for researchers to visit several different databases to answer one scientific question. It is essential to develop strategies to integrate disparate biological data sources that are efficient and seamless to facilitate the discovery of novel associations and validate existing hypotheses. This thesis presents the design and development of different integration strategies of biological and clinical systems. The BioSPIDA system is a data warehousing solution that integrates many NCBI databases and other biological sources on protein sequences, protein domains, and biological pathways. It utilizes a universal parser facilitating integration without developing separate source code for each data site. This enables users to execute fine-grained queries that can filter genes by their protein interactions, gene expressions, functional annotation, and protein domain representation. Relational databases can powerfully return and generate quickly filtered results to research questions, but they are not the most suitable solution in all cases. Clinical patients and genes are typically annotated by concepts in hierarchical ontologies and performance of relational databases are weakened considerably when traversing and representing graph structures. This thesis illustrates when relational databases are most suitable as well as comparing the performance benchmarks of semantic web technologies and graph databases when comparing ontological concepts. Several approaches of analyzing integrated data will be discussed to demonstrate the advantages over dependencies on remote data centers. Intensive Care Patients are prioritized by their length of stay and their severity class is estimated by their diagnosis to help minimize wait time and preferentially treat patients by their condition. In a separate study, semantic clustering of patients is conducted by integrating a clinical database and a medical ontology to help identify multi-morbidity patterns. In the biological area, gene pathways, protein interaction networks, and functional annotation are integrated to help predict and prioritize candidate disease genes. This thesis will present the results that were able to be generated from each project through utilizing a local repository of genes, functional annotations, protein interactions, clinical patients, and medical ontologies.

Avec la montée en charge de l’informatisation des systèmes d’information hospitaliers, une quantité croissante de données est produite tout au long de la prise en charge des patients. L’utilisation secondaire de ces données constitue un enjeu essentiel pour la recherche ou l’évaluation en santé. Dans le cadre de cette thèse, nous discutons les verrous liés à la représentation et à la sémantique des données, qui limitent leur utilisation secondaire en cancérologie. Nous proposons des méthodes basées sur des ontologies pour l’intégration sémantique des données de diagnostics. En effet, ces données sont représentées par des terminologies hétérogènes. Nous étendons les modèles obtenus pour la représentation de la maladie tumorale, et les liens qui existent avec les diagnostics. Enfin, nous proposons une architecture combinant entrepôts de données, registres de métadonnées et web sémantique. L’architecture proposée permet l’intégration syntaxique et sémantique d’un grand nombre d’observations. Par ailleurs, l’intégration de données et de connaissances (sous la forme d’ontologies) a été utilisée pour construire un algorithme d’identification de la maladie tumorale en fonction des diagnostics présents dans les données de prise en charge. Cet algorithme basé sur les classes de l’ontologie est indépendant des données effectivement enregistrées. Ainsi, il fait abstraction du caractère hétérogène des données diagnostiques initialement disponibles. L’approche basée sur une ontologie pour l’identification de la maladie tumorale, permet une adaptation rapide des règles d’agrégation en fonction des besoins spécifiques d’identification. Ainsi, plusieurs versions du modèle d’identification peuvent être utilisées avec des granularités différentes. / With the increasing adoption of Electronic Health Records (EHR), the amount of data produced at the patient bedside is rapidly increasing. Secondary use is there by an important field to investigate in order facilitate research and evaluation. In these work we discussed issues related to data representation and semantics within EHR that need to be address in order to facilitate secondary of structured data in oncology. We propose and evaluate ontology based methods for heterogeneous diagnosis terminologies integration in oncology. We then extend obtained model to enable tumoral disease representation and links with diagnosis as recorded in EHR. We then propose and implement a complete architecture combining a clinical data warehouse, a metadata registry and web semantic technologies and standards. This architecture enables syntactic and semantic integration of a broad range of hospital information System observation. Our approach links data with external knowledge (ontology), in order to provide a knowledge resource for an algorithm for tumoral disease identification based on diagnosis recorded within EHRs. As it based on the ontology classes, the identification algorithm is uses an integrated view of diagnosis (avoiding semantic heterogeneity). The proposed architecture leading to algorithm on the top of an ontology offers a flexible solution. Adapting the ontology, modifying for instance the granularity provide a way for adapting aggregation depending on specific needs