Glico-OralOma na perimplantite

Apesar da ênfase da medicina dentária preventiva nos últimos anos, continua a ser elevado o número de indivíduos parcial ou totalmente desdentados, necessitando de tratamentos que devolvam a funcionalidade. Nesse sentido, a implantologia tem-se tornado a área de eleição para que esses problemas sejam minimizados, proporcionando uma melhor qualidade de vida. A periimplantite, uma falha tardia dos implantes dentários, é definida como um processo inflamatório que afeta os tecidos circundantes de um implante osteointegrado em função, resultando na perda de osso de suporte. Esta patologia tem consequências tanto a nível económico como na saúde oral dos pacientes. Assim, urge identificar os mecanismos moleculares que estão envolvidos nesta patologia. O objetivo deste trabalho consiste e identificar as proteínas alteradas e as glicoproteínas cuja atividade possa ser modificada, de modo a identificar não só os processos moleculares que se encontram comprometidos na periimplantite, mas também esclarecer o contributo da flora que está presente de forma diferenciada nesta patologia. Recorrendo à biomedicina computacional, foi possível tratar dados no sentido de equacionar razões moleculares subjacentes à periimplantite. O estabelecimento do proteoma da periimplantite possibilitou adicionar 39 proteínas à base de dados OralCard, permitindo pela primeira vez compilar informação relativamente à periimplantite nesta base de dados. A caracterização funcional do OralOma da periimplantite permitiu identificar alterações em determinadas funções moleculares, processos biológicos e vias de sinalização. Não foi possível determinar o GlicOralOma devido à escassez de informações. Relativamente ao microbioma da periimplantite verificou-se existir escassez de estudos nesta área, sendo apenas identificados 5 géneros como aumentados na periimplantite. De igual forma, verificou-se uma escassez de dados que permitissem estabelecer relações com a periimplantite aquando da análise de interactómica. Este trabalho permitiu elucidar mecanismos moleculares que levam à perda óssea em redor do implante, o que poderá permitir o estabelecimento de alvos para futuros estudos experimentais e de novas abordagens na intervenção clínica na periimplantite.Despite the increased emphasis on preventive dentistry in recent years, remains high the number of partial or total edentulous people, requiring treatments that restore functionality. Therefore, implantology has become the main area of specialisation for these problems to be minimized, recovering quality of life. Peri-implantitis, the late failure of the dental implant, is an inflammatory process affecting the tissues surrounding an osseointegrated implant in function, resulting in the loss of supporting bone. This pathology has consequences both economically and in the oral health of patients. Thus, it is urgent to identify the molecular mechanisms that are involved on it. The aim of this work is to identify altered proteins and glycoproteins whose activity can be modified, in order to identify not only the molecular processes that are engaged in peri-implantitis, but also to clarify the contribution of flora that is present in different ways in this pathology. Using the computational biomedicine, it was possible to process data in order to equate molecular reasons underlying peri-implantitis. Establishing periimplantitis proteome allowed to add 39 proteins to OralCard database, making possible for the first time to compile periimplantitis information in this database. Functional characterization of the peri-implantitis OralOma led to identify changes in certain molecular functions, biological processes and signaling pathways. It was not possible to determine the Glyco-OralOme due to lack of information. Regarding the periimplantitis microbiome it was noted the lack of studies in this area, being only identified five genders as increased in peri-implantitis. Similarly, there was a paucity of data that would allow establishing relationships with peri-implantitis when of the interactomics examination. This work helped to clarify the molecular mechanisms that lead to bone loss around the implant, which may allow the establishment of targets for further experimental studies and new approaches in clinical intervention in peri-implantiti

Bioinformatics approaches to associate single nucleotide polymorphisms with human diseases according to their pathway related context

Genome-wide association studies (GWASs) with millions of single nucleotide polymorphisms (SNPs) are popular strategies to reveal the genetic basis of human complex diseases. Despite many successes of GWASs, it is well recognized that new analytical approaches have to be integrated to achieve their full potential. In this thesis, starting with a list of SNPs, found to be associated with disease in GWAS, we have developed a novel methodology to devise functionally important pathways through the identification of SNP targeted genes within these pathways. Our methodology is based on functionalization of important SNPs to identify effected genes and disease related pathways. We have tested our methodology on rheumatoid arthritis, epilepsy, intracranial aneurysm and Behçet’s disease datasets. With the whole-genome sequencing on the horizon, we show that the full potential of GWASs can be achieved by integrating prior knowledge from functional properties of a SNP and pathwayoriented analysis via protein-protein interaction networks