Machine Learning methods for hepatocellular malignancies segmentation and MVI prediction

The aim of this thesis project is to automatically localize HCC tumors in the human liver and subsequently predict if the tumor will undergo microvascular infiltration (MVI), the initial stage of metastasis development. The input data for the work have been partially supplied by Sant'Orsola Hospital and partially downloaded from online medical databases. Two Unet models have been implemented for the automatic segmentation of the livers and the HCC malignancies within it. The segmentation models have been evaluated with the Intersection-over-Union and the Dice Coefficient metrics. The outcomes obtained for the liver automatic segmentation are quite good (IOU = 0.82; DC = 0.35); the outcomes obtained for the tumor automatic segmentation (IOU = 0.35; DC = 0.46) are, instead, affected by some limitations: it can be state that the algorithm is almost always able to detect the location of the tumor, but it tends to underestimate its dimensions. The purpose is to achieve the CT images of the HCC tumors, necessary for features extraction. The 14 Haralick features calculated from the 3D-GLCM, the 120 Radiomic features and the patients' clinical information are collected to build a dataset of 153 features. Now, the goal is to build a model able to discriminate, based on the features given, the tumors that will undergo MVI and those that will not. This task can be seen as a classification problem: each tumor needs to be classified either as “MVI positive” or “MVI negative”. Techniques for features selection are implemented to identify the most descriptive features for the problem at hand and then, a set of classification models are trained and compared. Among all, the models with the best performances (around 80-84% ± 8-15%) result to be the XGBoost Classifier, the SDG Classifier and the Logist Regression models (without penalization and with Lasso, Ridge or Elastic Net penalization).

Development of advanced methods for the simulation of the reacting mixture formation in internal combustion engines with the use of machine learning algorithms

Besides increasing the share of electric and hybrid vehicles, in order to comply with more stringent environmental protection limitations, in the mid-term the auto industry must improve the efficiency of the internal combustion engine and the well to wheel efficiency of the employed fuel. To achieve this target, a deeper knowledge of the phenomena that influence the mixture formation and the chemical reactions involving new synthetic fuel components is mandatory, but complex and time intensive to perform purely by experimentation. Therefore, numerical simulations play an important role in this development process, but their use can be effective only if they can be considered accurate enough to capture these variations. The most relevant models necessary for the simulation of the reacting mixture formation and successive chemical reactions have been investigated in the present work, with a critical approach, in order to provide instruments to define the most suitable approaches also in the industrial context, which is limited by time constraints and budget evaluations. To overcome these limitations, new methodologies have been developed to conjugate detailed and simplified modelling techniques for the phenomena involving chemical reactions and mixture formation in non-traditional conditions (e.g. water injection, biofuels etc.). Thanks to the large use of machine learning and deep learning algorithms, several applications have been revised or implemented, with the target of reducing the computing time of some traditional tasks by orders of magnitude. Finally, a complete workflow leveraging these new models has been defined and used for evaluating the effects of different surrogate formulations of the same experimental fuel on a proof-of-concept GDI engine model.

Application of Deep Learning techniques in the search for BSM Higgs bosons in the $\mu\mu$ final state in CMS

The Standard Model (SM) of particle physics predicts the existence of a Higgs field responsible for the generation of particles' mass. However, some aspects of this theory remain unsolved, supposing the presence of new physics Beyond the Standard Model (BSM) with the production of new particles at a higher energy scale compared to the current experimental limits. The search for additional Higgs bosons is, in fact, predicted by theoretical extensions of the SM including the Minimal Supersymmetry Standard Model (MSSM). In the MSSM, the Higgs sector consists of two Higgs doublets, resulting in five physical Higgs particles: two charged bosons $H^{\pm}$, two neutral scalars $h$ and $H$, and one pseudoscalar $A$. The work presented in this thesis is dedicated to the search of neutral non-Standard Model Higgs bosons decaying to two muons in the model independent MSSM scenario. Proton-proton collision data recorded by the CMS experiment at the CERN LHC at a center-of-mass energy of 13 TeV are used, corresponding to an integrated luminosity of $35.9\ \text{fb}^{-1}$. Such search is sensitive to neutral Higgs bosons produced either via gluon fusion process or in association with a $\text{b}\bar{\text{b}}$ quark pair. The extensive usage of Machine and Deep Learning techniques is a fundamental element in the discrimination between signal and background simulated events. A new network structure called parameterised Neural Network (pNN) has been implemented, replacing a whole set of single neural networks trained at a specific mass hypothesis value with a single neural network able to generalise well and interpolate in the entire mass range considered. The results of the pNN signal/background discrimination are used to set a model independent 95\% confidence level expected upper limit on the production cross section times branching ratio, for a generic $\phi$ boson decaying into a muon pair in the 130 to 1000 GeV range.

Development and characterization of deep learning techniques for neuroimaging data

Deep learning methods are extremely promising machine learning tools to analyze neuroimaging data. However, their potential use in clinical settings is limited because of the existing challenges of applying these methods to neuroimaging data. In this study, first a data leakage type caused by slice-level data split that is introduced during training and validation of a 2D CNN is surveyed and a quantitative assessment of the model’s performance overestimation is presented. Second, an interpretable, leakage-fee deep learning software written in a python language with a wide range of options has been developed to conduct both classification and regression analysis. The software was applied to the study of mild cognitive impairment (MCI) in patients with small vessel disease (SVD) using multi-parametric MRI data where the cognitive performance of 58 patients measured by five neuropsychological tests is predicted using a multi-input CNN model taking brain image and demographic data. Each of the cognitive test scores was predicted using different MRI-derived features. As MCI due to SVD has been hypothesized to be the effect of white matter damage, DTI-derived features MD and FA produced the best prediction outcome of the TMT-A score which is consistent with the existing literature. In a second study, an interpretable deep learning system aimed at 1) classifying Alzheimer disease and healthy subjects 2) examining the neural correlates of the disease that causes a cognitive decline in AD patients using CNN visualization tools and 3) highlighting the potential of interpretability techniques to capture a biased deep learning model is developed. Structural magnetic resonance imaging (MRI) data of 200 subjects was used by the proposed CNN model which was trained using a transfer learning-based approach producing a balanced accuracy of 71.6%. Brain regions in the frontal and parietal lobe showing the cerebral cortex atrophy were highlighted by the visualization tools.

Machine learning as a service for high energy physics (MLaaS4HEP): a service for ML-based data analyses

With the CERN LHC program underway, there has been an acceleration of data growth in the High Energy Physics (HEP) field and the usage of Machine Learning (ML) in HEP will be critical during the HL-LHC program when the data that will be produced will reach the exascale. ML techniques have been successfully used in many areas of HEP nevertheless, the development of a ML project and its implementation for production use is a highly time-consuming task and requires specific skills. Complicating this scenario is the fact that HEP data is stored in ROOT data format, which is mostly unknown outside of the HEP community. The work presented in this thesis is focused on the development of a ML as a Service (MLaaS) solution for HEP, aiming to provide a cloud service that allows HEP users to run ML pipelines via HTTP calls. These pipelines are executed by using the MLaaS4HEP framework, which allows reading data, processing data, and training ML models directly using ROOT files of arbitrary size from local or distributed data sources. Such a solution provides HEP users non-expert in ML with a tool that allows them to apply ML techniques in their analyses in a streamlined manner. Over the years the MLaaS4HEP framework has been developed, validated, and tested and new features have been added. A first MLaaS solution has been developed by automatizing the deployment of a platform equipped with the MLaaS4HEP framework. Then, a service with APIs has been developed, so that a user after being authenticated and authorized can submit MLaaS4HEP workflows producing trained ML models ready for the inference phase. A working prototype of this service is currently running on a virtual machine of INFN-Cloud and is compliant to be added to the INFN Cloud portfolio of services.

Advancing digital healthcare research and machine learning-aided knowledge extraction amidst the COVID-19 pandemic

The rapid progression of biomedical research coupled with the explosion of scientific literature has generated an exigent need for efficient and reliable systems of knowledge extraction. This dissertation contends with this challenge through a concentrated investigation of digital health, Artificial Intelligence, and specifically Machine Learning and Natural Language Processing's (NLP) potential to expedite systematic literature reviews and refine the knowledge extraction process. The surge of COVID-19 complicated the efforts of scientists, policymakers, and medical professionals in identifying pertinent articles and assessing their scientific validity. This thesis presents a substantial solution in the form of the COKE Project, an initiative that interlaces machine reading with the rigorous protocols of Evidence-Based Medicine to streamline knowledge extraction. In the framework of the COKE (“COVID-19 Knowledge Extraction framework for next-generation discovery science”) Project, this thesis aims to underscore the capacity of machine reading to create knowledge graphs from scientific texts. The project is remarkable for its innovative use of NLP techniques such as a BERT + bi-LSTM language model. This combination is employed to detect and categorize elements within medical abstracts, thereby enhancing the systematic literature review process. The COKE project's outcomes show that NLP, when used in a judiciously structured manner, can significantly reduce the time and effort required to produce medical guidelines. These findings are particularly salient during times of medical emergency, like the COVID-19 pandemic, when quick and accurate research results are critical.

Network analysis and machine learning assist drug repurposing and safety assessment in neurological diseases

In recent decades, two prominent trends have influenced the data modeling field, namely network analysis and machine learning. This thesis explores the practical applications of these techniques within the domain of drug research, unveiling their multifaceted potential for advancing our comprehension of complex biological systems. The research undertaken during this PhD program is situated at the intersection of network theory, computational methods, and drug research. Across six projects presented herein, there is a gradual increase in model complexity. These projects traverse a diverse range of topics, with a specific emphasis on drug repurposing and safety in the context of neurological diseases. The aim of these projects is to leverage existing biomedical knowledge to develop innovative approaches that bolster drug research. The investigations have produced practical solutions, not only providing insights into the intricacies of biological systems, but also allowing the creation of valuable tools for their analysis. In short, the achievements are: • A novel computational algorithm to identify adverse events specific to fixed-dose drug combinations. • A web application that tracks the clinical drug research response to SARS-CoV-2. • A Python package for differential gene expression analysis and the identification of key regulatory "switch genes". • The identification of pivotal events causing drug-induced impulse control disorders linked to specific medications. • An automated pipeline for discovering potential drug repurposing opportunities. • The creation of a comprehensive knowledge graph and development of a graph machine learning model for predictions. Collectively, these projects illustrate diverse applications of data science and network-based methodologies, highlighting the profound impact they can have in supporting drug research activities.

Synthetic data generation for the assessment of antimicrobial resistance through machine learning

As a consequence of the diffusion of next generation sequencing techniques, metagenomics databases have become one of the most promising repositories of information about features and behavior of microorganisms. One of the subjects that can be studied from those data are bacteria populations. Next generation sequencing techniques allow to study the bacteria population within an environment by sampling genetic material directly from it, without the needing of culturing a similar population in vitro and observing its behavior. As a drawback, it is quite complex to extract information from those data and usually there is more than one way to do that; AMR is no exception. In this study we will discuss how the quantified AMR, which regards the genotype of the bacteria, can be related to the bacteria phenotype and its actual level of resistance against the specific substance. In order to have a quantitative information about bacteria genotype, we will evaluate the resistome from the read libraries, aligning them against CARD database. With those data, we will test various machine learning algorithms for predicting the bacteria phenotype. The samples that we exploit should resemble those that could be obtained from a natural context, but are actually produced by a read libraries simulation tool. In this way we are able to design the populations with bacteria of known genotype, so that we can relay on a secure ground truth for training and testing our algorithms.

Methods for monitoring Machine Learning models

The following thesis aims to investigate the issues concerning the maintenance of a Machine Learning model over time, both about the versioning of the model itself and the data on which it is trained and about data monitoring tools and their distribution. The themes of Data Drift and Concept Drift were then explored and the performance of some of the most popular techniques in the field of Anomaly detection, such as VAE, PCA, and Monte Carlo Dropout, were evaluated.

Hand gesture recognition system based in computer vision and machine learning : applications on human-machine interaction

Sendo uma forma natural de interação homem-máquina, o reconhecimento de gestos implica uma forte componente de investigação em áreas como a visão por computador e a aprendizagem computacional. O reconhecimento gestual é uma área com aplicações muito diversas, fornecendo aos utilizadores uma forma mais natural e mais simples de comunicar com sistemas baseados em computador, sem a necessidade de utilização de dispositivos extras. Assim, o objectivo principal da investigação na área de reconhecimento de gestos aplicada à interacção homemmáquina é o da criação de sistemas, que possam identificar gestos específicos e usálos para transmitir informações ou para controlar dispositivos. Para isso as interfaces baseados em visão para o reconhecimento de gestos, necessitam de detectar a mão de forma rápida e robusta e de serem capazes de efetuar o reconhecimento de gestos em tempo real. Hoje em dia, os sistemas de reconhecimento de gestos baseados em visão são capazes de trabalhar com soluções específicas, construídos para resolver um determinado problema e configurados para trabalhar de uma forma particular. Este projeto de investigação estudou e implementou soluções, suficientemente genéricas, com o recurso a algoritmos de aprendizagem computacional, permitindo a sua aplicação num conjunto alargado de sistemas de interface homem-máquina, para reconhecimento de gestos em tempo real. A solução proposta, Gesture Learning Module Architecture (GeLMA), permite de forma simples definir um conjunto de comandos que pode ser baseado em gestos estáticos e dinâmicos e que pode ser facilmente integrado e configurado para ser utilizado numa série de aplicações. É um sistema de baixo custo e fácil de treinar e usar, e uma vez que é construído unicamente com bibliotecas de código. As experiências realizadas permitiram mostrar que o sistema atingiu uma precisão de 99,2% em termos de reconhecimento de gestos estáticos e uma precisão média de 93,7% em termos de reconhecimento de gestos dinâmicos. Para validar a solução proposta, foram implementados dois sistemas completos. O primeiro é um sistema em tempo real capaz de ajudar um árbitro a arbitrar um jogo de futebol robótico. A solução proposta combina um sistema de reconhecimento de gestos baseada em visão com a definição de uma linguagem formal, o CommLang Referee, à qual demos a designação de Referee Command Language Interface System (ReCLIS). O sistema identifica os comandos baseados num conjunto de gestos estáticos e dinâmicos executados pelo árbitro, sendo este posteriormente enviado para um interface de computador que transmite a respectiva informação para os robôs. O segundo é um sistema em tempo real capaz de interpretar um subconjunto da Linguagem Gestual Portuguesa. As experiências demonstraram que o sistema foi capaz de reconhecer as vogais em tempo real de forma fiável. Embora a solução implementada apenas tenha sido treinada para reconhecer as cinco vogais, o sistema é facilmente extensível para reconhecer o resto do alfabeto. As experiências também permitiram mostrar que a base dos sistemas de interação baseados em visão pode ser a mesma para todas as aplicações e, deste modo facilitar a sua implementação. A solução proposta tem ainda a vantagem de ser suficientemente genérica e uma base sólida para o desenvolvimento de sistemas baseados em reconhecimento gestual que podem ser facilmente integrados com qualquer aplicação de interface homem-máquina. A linguagem formal de definição da interface pode ser redefinida e o sistema pode ser facilmente configurado e treinado com um conjunto de gestos diferentes de forma a serem integrados na solução final.

Machine learning Vasicek model calibration with Gaussian processes

In this article, we calibrate the Vasicek interest rate model under the risk neutral measure by learning the model parameters using Gaussian processes for machine learning regression. The calibration is done by maximizing the likelihood of zero coupon bond log prices, using mean and covariance functions computed analytically, as well as likelihood derivatives with respect to the parameters. The maximization method used is the conjugate gradients. The only prices needed for calibration are zero coupon bond prices and the parameters are directly obtained in the arbitrage free risk neutral measure.

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Dissertação para obtenção do Grau de Mestre em Engenharia Informática