Development of unsupervised learning methods with applications to life sciences data

Machine Learning makes computers capable of performing tasks typically requiring human intelligence. A domain where it is having a considerable impact is the life sciences, allowing to devise new biological analysis protocols, develop patients’ treatments efficiently and faster, and reduce healthcare costs. This Thesis work presents new Machine Learning methods and pipelines for the life sciences focusing on the unsupervised field. At a methodological level, two methods are presented. The first is an “Ab Initio Local Principal Path” and it is a revised and improved version of a pre-existing algorithm in the manifold learning realm. The second contribution is an improvement over the Import Vector Domain Description (one-class learning) through the Kullback-Leibler divergence. It hybridizes kernel methods to Deep Learning obtaining a scalable solution, an improved probabilistic model, and state-of-the-art performances. Both methods are tested through several experiments, with a central focus on their relevance in life sciences. Results show that they improve the performances achieved by their previous versions. At the applicative level, two pipelines are presented. The first one is for the analysis of RNA-Seq datasets, both transcriptomic and single-cell data, and is aimed at identifying genes that may be involved in biological processes (e.g., the transition of tissues from normal to cancer). In this project, an R package is released on CRAN to make the pipeline accessible to the bioinformatic Community through high-level APIs. The second pipeline is in the drug discovery domain and is useful for identifying druggable pockets, namely regions of a protein with a high probability of accepting a small molecule (a drug). Both these pipelines achieve remarkable results. Lastly, a detour application is developed to identify the strengths/limitations of the “Principal Path” algorithm by analyzing Convolutional Neural Networks induced vector spaces. This application is conducted in the music and visual arts domains.

Indicatori di correlazione e di disordine basati sul concetto di entropia

The aim of this work is to carry out an applicative, comparative and exhaustive study between several entropy based indicators of independence and correlation. We considered some indicators characterized by a wide and consolidate literature, like mutual information, joint entropy, relative entropy or Kullback Leibler distance, and others, more recently introduced, like Granger, Maasoumi and racine entropy, also called Sρ, or utilized in more restricted domains, like Pincus approximate entropy or ApEn. We studied the behaviour of such indicators applying them to binary series. The series was designed to simulate a wide range of situations in order to characterize indicators limit and capability and to identify, case by case, the more useful and trustworthy ones. Our target was not only to study if such indicators were able to discriminate between dependence and independence because, especially for mutual information and Granger, Maasoumi and Racine, that was already demonstrated and reported in literature, but also to verify if and how they were able to provide information about structure, complexity and disorder of the series they were applied to. Special attention was paid on Pincus approximate entropy, that is said by the author to be able to provide information regarding the level of randomness, regularity and complexity of a series. By means of a focused and extensive research, we furthermore tried to clear the meaning of ApEn applied to a couple of different series. In such situation the indicator is named in literature as cross-ApEn. The cross-ApEn meaning and the interpretation of its results is often not simple nor univocal and the matter is scarcely delved into by literature, thereby users can easily leaded up to a misleading conclusion, especially if the indicator is employed, as often unfortunately it happens, in uncritical manner. In order to plug some cross-ApEn gaps and limits clearly brought out during the experimentation, we developed and applied to the already considered cases a further indicator we called “correspondence index”. The correspondence index is perfectly integrated into the cross-ApEn computational algorithm and it is able to provide, at least for binary data, accurate information about the intensity and the direction of an eventual correlation, even not linear, existing between two different series allowing, in the meanwhile, to detect an eventual condition of independence between the series themselves.

Transatlantic regulatory divergence in pharmaceuticals: exploring economic and cultural explanations

The analysis delves into the regulatory divergence between the EU and the US in the pharmaceutical sector. Through law and economics, political science, and cultural theory perspectives, the study explores how collective preferences within each jurisdiction shape regulations. By identifying cultural orientations such as individualism in the US and hierarchy in the EU, the research suggests that underlying cultural factors play a significant role in regulatory decisions. Despite calls for regulatory harmonization, the recognition of legitimate differences in preferences due to cultural diversity emphasizes that uniformity may not always be the best solution, showcasing the importance of understanding cultural influences in shaping regulatory landscapes.