Clustering of variables around latent components: an application in consumer science

The present work proposes a method based on CLV (Clustering around Latent Variables) for identifying groups of consumers in L-shape data. This kind of datastructure is very common in consumer studies where a panel of consumers is asked to assess the global liking of a certain number of products and then, preference scores are arranged in a two-way table Y. External information on both products (physicalchemical description or sensory attributes) and consumers (socio-demographic background, purchase behaviours or consumption habits) may be available in a row descriptor matrix X and in a column descriptor matrix Z respectively. The aim of this method is to automatically provide a consumer segmentation where all the three matrices play an active role in the classification, getting homogeneous groups from all points of view: preference, products and consumer characteristics. The proposed clustering method is illustrated on data from preference studies on food products: juices based on berry fruits and traditional cheeses from Trentino. The hedonic ratings given by the consumer panel on the products under study were explained with respect to the product chemical compounds, sensory evaluation and consumer socio-demographic information, purchase behaviour and consumption habits.

Measure of Global Specialization and Spatial Clustering for the Identification of "Specialized" Agglomeration

The intensity of regional specialization in specific activities, and conversely, the level of industrial concentration in specific locations, has been used as a complementary evidence for the existence and significance of externalities. Additionally, economists have mainly focused the debate on disentangling the sources of specialization and concentration processes according to three vectors: natural advantages, internal, and external scale economies. The arbitrariness of partitions plays a key role in capturing these effects, while the selection of the partition would have to reflect the actual characteristics of the economy. Thus, the identification of spatial boundaries to measure specialization becomes critical, since most likely the model will be adapted to different scales of distance, and be influenced by different types of externalities or economies of agglomeration, which are based on the mechanisms of interaction with particular requirements of spatial proximity. This work is based on the analysis of the spatial aspect of economic specialization supported by the manufacturing industry case. The main objective is to propose, for discrete and continuous space: i) a measure of global specialization; ii) a local disaggregation of the global measure; and iii) a spatial clustering method for the identification of specialized agglomerations.

Development of a new galaxy classification technique and its application to the zCOSMOS survey

The purpose of this Thesis is to develop a robust and powerful method to classify galaxies from large surveys, in order to establish and confirm the connections between the principal observational parameters of the galaxies (spectral features, colours, morphological indices), and help unveil the evolution of these parameters from $z \sim 1$ to the local Universe. Within the framework of zCOSMOS-bright survey, and making use of its large database of objects ($\sim 10\,000$ galaxies in the redshift range $0 < z \lesssim 1.2$) and its great reliability in redshift and spectral properties determinations, first we adopt and extend the \emph{classification cube method}, as developed by Mignoli et al. (2009), to exploit the bimodal properties of galaxies (spectral, photometric and morphologic) separately, and then combining together these three subclassifications. We use this classification method as a test for a newly devised statistical classification, based on Principal Component Analysis and Unsupervised Fuzzy Partition clustering method (PCA+UFP), which is able to define the galaxy population exploiting their natural global bimodality, considering simultaneously up to 8 different properties. The PCA+UFP analysis is a very powerful and robust tool to probe the nature and the evolution of galaxies in a survey. It allows to define with less uncertainties the classification of galaxies, adding the flexibility to be adapted to different parameters: being a fuzzy classification it avoids the problems due to a hard classification, such as the classification cube presented in the first part of the article. The PCA+UFP method can be easily applied to different datasets: it does not rely on the nature of the data and for this reason it can be successfully employed with others observables (magnitudes, colours) or derived properties (masses, luminosities, SFRs, etc.). The agreement between the two classification cluster definitions is very high. ``Early'' and ``late'' type galaxies are well defined by the spectral, photometric and morphological properties, both considering them in a separate way and then combining the classifications (classification cube) and treating them as a whole (PCA+UFP cluster analysis). Differences arise in the definition of outliers: the classification cube is much more sensitive to single measurement errors or misclassifications in one property than the PCA+UFP cluster analysis, in which errors are ``averaged out'' during the process. This method allowed us to behold the \emph{downsizing} effect taking place in the PC spaces: the migration between the blue cloud towards the red clump happens at higher redshifts for galaxies of larger mass. The determination of $M_{\mathrm{cross}}$ the transition mass is in significant agreement with others values in literature.

Comparing Different Approaches for Clustering Categorical Data

There are different ways to do cluster analysis of categorical data in the literature and the choice among them is strongly related to the aim of the researcher, if we do not take into account time and economical constraints. Main approaches for clustering are usually distinguished into model-based and distance-based methods: the former assume that objects belonging to the same class are similar in the sense that their observed values come from the same probability distribution, whose parameters are unknown and need to be estimated; the latter evaluate distances among objects by a defined dissimilarity measure and, basing on it, allocate units to the closest group. In clustering, one may be interested in the classification of similar objects into groups, and one may be interested in finding observations that come from the same true homogeneous distribution. But do both of these aims lead to the same clustering? And how good are clustering methods designed to fulfil one of these aims in terms of the other? In order to answer, two approaches, namely a latent class model (mixture of multinomial distributions) and a partition around medoids one, are evaluated and compared by Adjusted Rand Index, Average Silhouette Width and Pearson-Gamma indexes in a fairly wide simulation study. Simulation outcomes are plotted in bi-dimensional graphs via Multidimensional Scaling; size of points is proportional to the number of points that overlap and different colours are used according to the cluster membership.

adaptive capabilities of the pi3k/akt/mtor pathway in acute myeloid leukemia revealed by the use of selective inhibitors

Because of its aberrant activation, the PI3K/AKT/mTOR signaling pathway represents a pharmacological target in blast cells from patients with acute myelogenous leukemia (AML). Using Reverse Phase Protein Microarrays (RPMA), we have analyzed 20 phosphorylated epitopes of the PI3K/Akt/mTor signal pathway of peripheral blood and bone marrow specimens of 84 patients with newly diagnosed AML. Fresh blast cells were grown for 2 h, 4 h or 20 h untreated or treated with a panel of phase I or phase II Akt allosteric inhibitors, either alone or in combination with the mTOR kinase inhibitor Torin1 or the broad RTK inhibitor Sunitinib. By unsupervised hierarchical clustering a strong phosphorylation/activity of most of the sampled members of the PI3K/Akt/mTOR pathway was observed in 70% of samples from AML patients. Remarkably, however, we observed that inhibition of Akt phosphorylation, as well as of its substrates, was transient, and recovered or even increased far above basal level after 20 h in 60% samples. We demonstrated that inhibition of Akt induces FOXO-dependent insulin receptor expression and IRS-1 activation, attenuating the effect of drug treatment by reactivation of PI3K/Akt. Consistent with this model we found that combined inhibition of Akt and RTKs is much more effective than either alone, revealing the adaptive capabilities of signaling networks in blast cells and highliting the limations of these drugs if used as monotherapy.

A clustering method for robust and reliable large scale functional and structural protein sequence annotation

Bioinformatics, in the last few decades, has played a fundamental role to give sense to the huge amount of data produced. Obtained the complete sequence of a genome, the major problem of knowing as much as possible of its coding regions, is crucial. Protein sequence annotation is challenging and, due to the size of the problem, only computational approaches can provide a feasible solution. As it has been recently pointed out by the Critical Assessment of Function Annotations (CAFA), most accurate methods are those based on the transfer-by-homology approach and the most incisive contribution is given by cross-genome comparisons. In the present thesis it is described a non-hierarchical sequence clustering method for protein automatic large-scale annotation, called “The Bologna Annotation Resource Plus” (BAR+). The method is based on an all-against-all alignment of more than 13 millions protein sequences characterized by a very stringent metric. BAR+ can safely transfer functional features (Gene Ontology and Pfam terms) inside clusters by means of a statistical validation, even in the case of multi-domain proteins. Within BAR+ clusters it is also possible to transfer the three dimensional structure (when a template is available). This is possible by the way of cluster-specific HMM profiles that can be used to calculate reliable template-to-target alignments even in the case of distantly related proteins (sequence identity < 30%). Other BAR+ based applications have been developed during my doctorate including the prediction of Magnesium binding sites in human proteins, the ABC transporters superfamily classification and the functional prediction (GO terms) of the CAFA targets. Remarkably, in the CAFA assessment, BAR+ placed among the ten most accurate methods. At present, as a web server for the functional and structural protein sequence annotation, BAR+ is freely available at http://bar.biocomp.unibo.it/bar2.0.

Unsupervised reinforcement learning via state entropy maximization

Reinforcement Learning (RL) provides a powerful framework to address sequential decision-making problems in which the transition dynamics is unknown or too complex to be represented. The RL approach is based on speculating what is the best decision to make given sample estimates obtained from previous interactions, a recipe that led to several breakthroughs in various domains, ranging from game playing to robotics. Despite their success, current RL methods hardly generalize from one task to another, and achieving the kind of generalization obtained through unsupervised pre-training in non-sequential problems seems unthinkable. Unsupervised RL has recently emerged as a way to improve generalization of RL methods. Just as its non-sequential counterpart, the unsupervised RL framework comprises two phases: An unsupervised pre-training phase, in which the agent interacts with the environment without external feedback, and a supervised fine-tuning phase, in which the agent aims to efficiently solve a task in the same environment by exploiting the knowledge acquired during pre-training. In this thesis, we study unsupervised RL via state entropy maximization, in which the agent makes use of the unsupervised interactions to pre-train a policy that maximizes the entropy of its induced state distribution. First, we provide a theoretical characterization of the learning problem by considering a convex RL formulation that subsumes state entropy maximization. Our analysis shows that maximizing the state entropy in finite trials is inherently harder than RL. Then, we study the state entropy maximization problem from an optimization perspective. Especially, we show that the primal formulation of the corresponding optimization problem can be (approximately) addressed through tractable linear programs. Finally, we provide the first practical methodologies for state entropy maximization in complex domains, both when the pre-training takes place in a single environment as well as multiple environments.

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.