An investigation of imputation methods for discrete databases and multi-variate time series

When it comes to information sets in real life, often pieces of the whole set may not be available. This problem can find its origin in various reasons, describing therefore different patterns. In the literature, this problem is known as Missing Data. This issue can be fixed in various ways, from not taking into consideration incomplete observations, to guessing what those values originally were, or just ignoring the fact that some values are missing. The methods used to estimate missing data are called Imputation Methods. The work presented in this thesis has two main goals. The first one is to determine whether any kind of interactions exists between Missing Data, Imputation Methods and Supervised Classification algorithms, when they are applied together. For this first problem we consider a scenario in which the databases used are discrete, understanding discrete as that it is assumed that there is no relation between observations. These datasets underwent processes involving different combina- tions of the three components mentioned. The outcome showed that the missing data pattern strongly influences the outcome produced by a classifier. Also, in some of the cases, the complex imputation techniques investigated in the thesis were able to obtain better results than simple ones. The second goal of this work is to propose a new imputation strategy, but this time we constrain the specifications of the previous problem to a special kind of datasets, the multivariate Time Series. We designed new imputation techniques for this particular domain, and combined them with some of the contrasted strategies tested in the pre- vious chapter of this thesis. The time series also were subjected to processes involving missing data and imputation to finally propose an overall better imputation method. In the final chapter of this work, a real-world example is presented, describing a wa- ter quality prediction problem. The databases that characterized this problem had their own original latent values, which provides a real-world benchmark to test the algorithms developed in this thesis.

Identification of a biomarker panel for colorectal cancer diagnosis

Background: Malignancies arising in the large bowel cause the second largest number of deaths from cancer in the Western World. Despite progresses made during the last decades, colorectal cancer remains one of the most frequent and deadly neoplasias in the western countries. Methods: A genomic study of human colorectal cancer has been carried out on a total of 31 tumoral samples, corresponding to different stages of the disease, and 33 non-tumoral samples. The study was carried out by hybridisation of the tumour samples against a reference pool of non-tumoral samples using Agilent Human 1A 60- mer oligo microarrays. The results obtained were validated by qRT-PCR. In the subsequent bioinformatics analysis, gene networks by means of Bayesian classifiers, variable selection and bootstrap resampling were built. The consensus among all the induced models produced a hierarchy of dependences and, thus, of variables. Results: After an exhaustive process of pre-processing to ensure data quality–lost values imputation, probes quality, data smoothing and intraclass variability filtering–the final dataset comprised a total of 8, 104 probes. Next, a supervised classification approach and data analysis was carried out to obtain the most relevant genes. Two of them are directly involved in cancer progression and in particular in colorectal cancer. Finally, a supervised classifier was induced to classify new unseen samples. Conclusions: We have developed a tentative model for the diagnosis of colorectal cancer based on a biomarker panel. Our results indicate that the gene profile described herein can discriminate between non-cancerous and cancerous samples with 94.45% accuracy using different supervised classifiers (AUC values in the range of 0.997 and 0.955).