[pt] A presente tese se insere no contexto de previsão de séries temporais. Nesse sentido, embora muitas abordagens tenham sido desenvolvidas, métodos simples como o de amortecimento exponencial costumam gerar resultados extremamente competitivos muitas vezes superando abordagens com maior nível de complexidade. No contexto previsão, papers seminais na área mostraram que a combinação de previsões tem potencial para reduzir de maneira acentuada o erro de previsão. Especificamente, a combinação de previsões geradas por amortecimento exponencial tem sido explorada em papers recentes. Apesar da combinação de previsões utilizando Amortecimento Exponencial poder ser feita de diversas formas, um método proposto recentemente e chamado de Bagged.BLD.MBB.ETS utiliza uma técnica chamada Bootstrap Aggregating (Bagging) em combinação com métodos de amortecimento exponencial para gerar previsões mostrando que a abordagem é capaz de gerar previsões mensais mais precisas que todos os benchmarks analisados. A abordagem era considerada o estado da arte na utilização de Bagging e Amortecimento Exponencial até o desenvolvimento dos resultados obtidos nesta tese. A tese em questão se ocupa de, inicialmente, validar o método Bagged.BLD.MBB.ETS em um conjunto de dados relevante do ponto de vista de uma aplicação real, expandindo assim os campos de aplicação da metodologia. Posteriormente, são identificados motivos relevantes para redução do erro de e é proposta uma nova metodologia que utiliza Bagging, Amortecimento Exponencial e Clusters para tratar o efeito covariância, até então não identificado anteriormente na literatura do método. A abordagem proposta foi testada utilizando diferentes tipo de séries temporais da competição M3, CIF 2016 e M4, bem como utilizando dados simulados. Os resultados empíricos apontam para uma redução substancial na variância e no erro de previsão. / [en] This thesis is inserted in the context of time series forecasting. In this sense, although many approaches have been developed, simple methods such as exponential smoothing usually produce extremely competitive results, often surpassing approaches with a higher level of complexity. Seminal papers in time series forecasting showed that the combination of forecasts has the potential to dramatically reduce the forecast error. Specifically, the combination of forecasts generated by Exponential Smoothing has been explored in recent papers. Although this can be done in many ways, a specific method called Bagged.BLD.MBB.ETS uses a technique called Bootstrap Aggregating (Bagging) in combination with Exponential Smoothing methods to generate forecasts, showing that the approach can generate more accurate monthly forecasts than all the analyzed benchmarks. The approach was considered the state of the art in the use of Bagging and Exponential Smoothing until the development of the results obtained in this thesis. This thesis initially deals with validating Bagged.BLD.MBB.ETS in a data set relevant from the point of view of a real application, thus expanding the fields of application of the methodology. Subsequently, relevant motifs for error reduction are identified and a new methodology using Bagging, Exponential Smoothing and Clusters is proposed to treat the covariance effect, not previously identified in the method s literature. The proposed approach was tested using data from three time series competitions (M3, CIF 2016 and M4), as well as using simulated data. The empirical results point to a substantial reduction in variance and forecast error.

Decoding the genomes from organisms that encompass all taxonomies provides the foundation for extensive, large scale studies of biological molecules such as RNA, protein and carbohydrates. The high-throughput studies facilitated by the existence of these genome sequences necessitate the development of new analytic methods for the interpretation of large sets of results. The work herein focuses on the development of a novel clustering method for the analysis of protein array results and examines its utilization in the analysis of integrated interaction data sets. Sets of proteins that interact with a molecule of interest were clustered according to their functional similarity. The simUI distance metric in the statistical analysis package BioConductor was applied to measure the similarity of two proteins utilizing the assembly of their Gene Ontology annotation. Clusters were identified by partitioning around medoids and interpreted using the summary label provided by the Gene Ontology annotation of the medoid. The utility of the method was tested on two published yeast protein array data sets and shown to allow interpretation of the data to yield novel biological hypotheses. We performed a protein array screen using the E3 ubiquitin ligase and PDZ domain-containing protein LNX1. We combined these results with other published LNX1 interactors to produce a set of 220 proteins that was clustered according to Gene Ontology annotation. From the clustering results, 14 proteins were selected for subsequent examination by co-immunoprecipitation, of which 8 proteins were confirmed as LNX1 interactors. Recognition of 6 proteins by specific LNX1 PDZ domains was confirmed by fusion protein pull-downs. This work supports the role of LNX1 as a signalling scaffold. The interpretation of protein array results using our novel clustering method facilitated the identification of candidate molecules for subsequent experimental analysis. Thus our analytical method facilitates identification of biologically relevant molecules within a large data set, making this method an essential component of complex, high-throughput experimentation.

Decoding the genomes from organisms that encompass all taxonomies provides the foundation for extensive, large scale studies of biological molecules such as RNA, protein and carbohydrates. The high-throughput studies facilitated by the existence of these genome sequences necessitate the development of new analytic methods for the interpretation of large sets of results. The work herein focuses on the development of a novel clustering method for the analysis of protein array results and examines its utilization in the analysis of integrated interaction data sets. Sets of proteins that interact with a molecule of interest were clustered according to their functional similarity. The simUI distance metric in the statistical analysis package BioConductor was applied to measure the similarity of two proteins utilizing the assembly of their Gene Ontology annotation. Clusters were identified by partitioning around medoids and interpreted using the summary label provided by the Gene Ontology annotation of the medoid. The utility of the method was tested on two published yeast protein array data sets and shown to allow interpretation of the data to yield novel biological hypotheses. We performed a protein array screen using the E3 ubiquitin ligase and PDZ domain-containing protein LNX1. We combined these results with other published LNX1 interactors to produce a set of 220 proteins that was clustered according to Gene Ontology annotation. From the clustering results, 14 proteins were selected for subsequent examination by co-immunoprecipitation, of which 8 proteins were confirmed as LNX1 interactors. Recognition of 6 proteins by specific LNX1 PDZ domains was confirmed by fusion protein pull-downs. This work supports the role of LNX1 as a signalling scaffold. The interpretation of protein array results using our novel clustering method facilitated the identification of candidate molecules for subsequent experimental analysis. Thus our analytical method facilitates identification of biologically relevant molecules within a large data set, making this method an essential component of complex, high-throughput experimentation.