Methods for Biodata Analysis in different Omic Contexts

The world of Computational Biology and Bioinformatics presently integrates many different expertise, including computer science and electronic engineering. A major aim in Data Science is the development and tuning of specific computational approaches to interpret the complexity of Biology. Molecular biologists and medical doctors heavily rely on an interdisciplinary expert capable of understanding the biological background to apply algorithms for finding optimal solutions to their problems. With this problem-solving orientation, I was involved in two basic research fields: Cancer Genomics and Enzyme Proteomics. For this reason, what I developed and implemented can be considered a general effort to help data analysis both in Cancer Genomics and in Enzyme Proteomics, focusing on enzymes which catalyse all the biochemical reactions in cells. Specifically, as to Cancer Genomics I contributed to the characterization of intratumoral immune microenvironment in gastrointestinal stromal tumours (GISTs) correlating immune cell population levels with tumour subtypes. I was involved in the setup of strategies for the evaluation and standardization of different approaches for fusion transcript detection in sarcomas that can be applied in routine diagnostic. This was part of a coordinated effort of the Sarcoma working group of "Alleanza Contro il Cancro". As to Enzyme Proteomics, I generated a derived database collecting all the human proteins and enzymes which are known to be associated to genetic disease. I curated the data search in freely available databases such as PDB, UniProt, Humsavar, Clinvar and I was responsible of searching, updating, and handling the information content, and computing statistics. I also developed a web server, BENZ, which allows researchers to annotate an enzyme sequence with the corresponding Enzyme Commission number, the important feature fully describing the catalysed reaction. More to this, I greatly contributed to the characterization of the enzyme-genetic disease association, for a better classification of the metabolic genetic diseases.

Assessing the fit of unidimensional IRT models for binary data under model misspecification

Model misspecification affects the classical test statistics used to assess the fit of the Item Response Theory (IRT) models. Robust tests have been derived under model misspecification, as the Generalized Lagrange Multiplier and Hausman tests, but their use has not been largely explored in the IRT framework. In the first part of the thesis, we introduce the Generalized Lagrange Multiplier test to detect differential item response functioning in IRT models for binary data under model misspecification. By means of a simulation study and a real data analysis, we compare its performance with the classical Lagrange Multiplier test, computed using the Hessian and the cross-product matrix, and the Generalized Jackknife Score test. The power of these tests is computed empirically and asymptotically. The misspecifications considered are local dependence among items and non-normal distribution of the latent variable. The results highlight that, under mild model misspecification, all tests have good performance while, under strong model misspecification, the performance of the tests deteriorates. None of the tests considered show an overall superior performance than the others. In the second part of the thesis, we extend the Generalized Hausman test to detect non-normality of the latent variable distribution. To build the test, we consider a seminonparametric-IRT model, that assumes a more flexible latent variable distribution. By means of a simulation study and two real applications, we compare the performance of the Generalized Hausman test with the M2 limited information goodness-of-fit test and the Likelihood-Ratio test. Additionally, the information criteria are computed. The Generalized Hausman test has a better performance than the Likelihood-Ratio test in terms of Type I error rates and the M2 test in terms of power. The performance of the Generalized Hausman test and the information criteria deteriorates when the sample size is small and with a few items.

Formare competenze per gestire processi di Open Innovation. Uno studio di caso.

Per comprende più a fondo il problema che le aziende affrontare per formare le persone in grado di gestire processi di innovazione, in particolare di Open Innovation (OI), è stato realizzato nel 2021 uno studio di caso multiplo di un percorso di educazione non formale all’OI realizzato dalla società consortile ART-ER e rivolto ai dottorandi degli atenei emiliano-romagnoli. Nella seconda fase di tale percorso formativo, per rispondere alle sfide di OI lanciate dalle aziende, sono stati costituiti 4 tavoli di lavoro. A ciascun tavolo di lavoro hanno preso parte 3/4 dottorandi, due referenti aziendali, un consulente e un operatore di ART-ER. Il campione complessivo era costituito da 14 dottorandi; 8 referenti aziendali di quattro aziende; 4 membri di una società di consulenza e 4 operatori della società consortile ART-ER. Il seguente interrogativo di ricerca ha guidato l’indagine: l’interazione tra i soggetti coinvolti in ciascun tavolo di lavoro – considerato un singolo caso - si configura come una Comunità di Pratica in grado di favorire lo sviluppo di apprendimenti individuali funzionali a gestire i processi di OI attivati nelle imprese? I dati sono stati raccolti attraverso una ricerca documentale a tavolino, focus group, interviste semistrutturate e un questionario semistrutturato online. L’analisi dei dati è stata effettuata mediante un’analisi qualitativa del contenuto in più fasi con l’ausilio del software MAXQDA. I risultati dimostrano che in tre casi su quattro, i tavoli di lavoro si sono configurati come una Comunità di Pratica. In questi tre tavoli inoltre è emerso lo sviluppo di alcune aree di competenza funzionali alla gestione dei processi di OI. Nella conclusione sono state presentate alcune proposte per la riprogettazione delle future edizioni del percorso formativo.

Data surveillance for infectious diseases: models, complex networks and machine learning

In this thesis, we investigate the role of applied physics in epidemiological surveillance through the application of mathematical models, network science and machine learning. The spread of a communicable disease depends on many biological, social, and health factors. The large masses of data available make it possible, on the one hand, to monitor the evolution and spread of pathogenic organisms; on the other hand, to study the behavior of people, their opinions and habits. Presented here are three lines of research in which an attempt was made to solve real epidemiological problems through data analysis and the use of statistical and mathematical models. In Chapter 1, we applied language-inspired Deep Learning models to transform influenza protein sequences into vectors encoding their information content. We then attempted to reconstruct the antigenic properties of different viral strains using regression models and to identify the mutations responsible for vaccine escape. In Chapter 2, we constructed a compartmental model to describe the spread of a bacterium within a hospital ward. The model was informed and validated on time series of clinical measurements, and a sensitivity analysis was used to assess the impact of different control measures. Finally (Chapter 3) we reconstructed the network of retweets among COVID-19 themed Twitter users in the early months of the SARS-CoV-2 pandemic. By means of community detection algorithms and centrality measures, we characterized users’ attention shifts in the network, showing that scientific communities, initially the most retweeted, lost influence over time to national political communities. In the Conclusion, we highlighted the importance of the work done in light of the main contemporary challenges for epidemiological surveillance. In particular, we present reflections on the importance of nowcasting and forecasting, the relationship between data and scientific research, and the need to unite the different scales of epidemiological surveillance.

Meaningful insights: explainability techniques for black-box models on tabular data

Artificial Intelligence (AI) and Machine Learning (ML) are novel data analysis techniques providing very accurate prediction results. They are widely adopted in a variety of industries to improve efficiency and decision-making, but they are also being used to develop intelligent systems. Their success grounds upon complex mathematical models, whose decisions and rationale are usually difficult to comprehend for human users to the point of being dubbed as black-boxes. This is particularly relevant in sensitive and highly regulated domains. To mitigate and possibly solve this issue, the Explainable AI (XAI) field became prominent in recent years. XAI consists of models and techniques to enable understanding of the intricated patterns discovered by black-box models. In this thesis, we consider model-agnostic XAI techniques, which can be applied to Tabular data, with a particular focus on the Credit Scoring domain. Special attention is dedicated to the LIME framework, for which we propose several modifications to the vanilla algorithm, in particular: a pair of complementary Stability Indices that accurately measure LIME stability, and the OptiLIME policy which helps the practitioner finding the proper balance among explanations' stability and reliability. We subsequently put forward GLEAMS a model-agnostic surrogate interpretable model which requires to be trained only once, while providing both Local and Global explanations of the black-box model. GLEAMS produces feature attributions and what-if scenarios, from both dataset and model perspective. Eventually, we argue that synthetic data are an emerging trend in AI, being more and more used to train complex models instead of original data. To be able to explain the outcomes of such models, we must guarantee that synthetic data are reliable enough to be able to translate their explanations to real-world individuals. To this end we propose DAISYnt, a suite of tests to measure synthetic tabular data quality and privacy.