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.

Uncovering the encoding and transmission of behaviourally relevant information in neural activity

Most cognitive functions require the encoding and routing of information across distributed networks of brain regions. Information propagation is typically attributed to physical connections existing between brain regions, and contributes to the formation of spatially correlated activity patterns, known as functional connectivity. While structural connectivity provides the anatomical foundation for neural interactions, the exact manner in which it shapes functional connectivity is complex and not yet fully understood. Additionally, traditional measures of directed functional connectivity only capture the overall correlation between neural activity, and provide no insight on the content of transmitted information, limiting their ability in understanding neural computations underlying the distributed processing of behaviorally-relevant variables. In this work, we first study the relationship between structural and functional connectivity in simulated recurrent spiking neural networks with spike timing dependent plasticity. We use established measures of time-lagged correlation and overall information propagation to infer the temporal evolution of synaptic weights, showing that measures of dynamic functional connectivity can be used to reliably reconstruct the evolution of structural properties of the network. Then, we extend current methods of directed causal communication between brain areas, by deriving an information-theoretic measure of Feature-specific Information Transfer (FIT) quantifying the amount, content and direction of information flow. We test FIT on simulated data, showing its key properties and advantages over traditional measures of overall propagated information. We show applications of FIT to several neural datasets obtained with different recording methods (magneto and electro-encephalography, spiking activity, local field potentials) during various cognitive functions, ranging from sensory perception to decision making and motor learning. Overall, these analyses demonstrate the ability of FIT to advance the investigation of communication between brain regions, uncovering the previously unaddressed content of directed information flow.

tecniche di machine learning per la predizione del rating delle applicazioni all’interno di un play store

Il mio progetto di tesi ha come obiettivo quello di creare un modello in grado di predire il rating delle applicazioni presenti all’interno del Play Store, uno dei più grandi servizi di distribuzione digitale Android. A tale scopo ho utilizzato il linguaggio Python, che grazie alle sue librerie, alla sua semplicità e alla sua versatilità è certamen- te uno dei linguaggi più usati nel campo dell’intelligenza artificiale. Il punto di partenza del mio studio è stato il Dataset (Insieme di dati strutturati in forma relazionale) “Google Play Store Apps” reperibile su Kaggle al seguente indirizzo: https://www.kaggle.com/datasets/lava18/google-play-store-apps, contenente 10841 osservazioni e 13 attributi. Dopo una prima parte relativa al caricamen- to, alla visualizzazione e alla preparazione dei dati su cui lavorare, ho applica- to quattro di↵erenti tecniche di Machine Learning per la stima del rating delle applicazioni. In particolare, sono state utilizzate:https://www.kaggle.com/datasets/lava18/google-play-store-apps, contenente 10841 osservazioni e 13 attributi. Dopo una prima parte relativa al caricamento, alla visualizzazione e alla preparazione dei dati su cui lavorare, ho applicato quattro differenti tecniche di Machine Learning per la stima del rating delle applicazioni: Ridje, Regressione Lineare, Random Forest e SVR. Tali algoritmi sono stati applicati attuando due tipi diversi di trasformazioni (Label Encoding e One Hot Encoding) sulla variabile ‘Category’, con lo scopo di analizzare come le suddette trasformazioni riescano a influire sulla bontà del modello. Ho confrontato poi l’errore quadratico medio (MSE), l’errore medio as- soluto (MAE) e l’errore mediano assoluto (MdAE) con il fine di capire quale sia l’algoritmo più efficiente.

Planning, operations and data handling of planetary science missions

Dissertação para obtenção do Grau de Mestre em Engenharia Física

Compositions in life science data

The aim of this talk is to convince the reader that there are a lot of interesting statisticalproblems in presentday life science data analysis which seem ultimately connected withcompositional statistics.Key words: SAGE, cDNA microarrays, (1D-)NMR, virus quasispecies

How Much Does It Cost? Optimization of Costs in Sequence Analysis of Social Science Data

One major methodological problem in analysis of sequence data is the determination of costs from which distances between sequences are derived. Although this problem is currently not optimally dealt with in the social sciences, it has some similarity with problems that have been solved in bioinformatics for three decades. In this article, the authors propose an optimization of substitution and deletion/insertion costs based on computational methods. The authors provide an empirical way of determining costs for cases, frequent in the social sciences, in which theory does not clearly promote one cost scheme over another. Using three distinct data sets, the authors tested the distances and cluster solutions produced by the new cost scheme in comparison with solutions based on cost schemes associated with other research strategies. The proposed method performs well compared with other cost-setting strategies, while it alleviates the justification problem of cost schemes.

A process for mining science & technology documents databases, illustrated for the case of "knowledge discovery and data mining"

This paper presents a process of mining research & development abstract databases to profile current status and to project potential developments for target technologies, The process is called "technology opportunities analysis." This article steps through the process using a sample data set of abstracts from the INSPEC database on the topic o "knowledge discovery and data mining." The paper offers a set of specific indicators suitable for mining such databases to understand innovation prospects. In illustrating the uses of such indicators, it offers some insights into the status of knowledge discovery research*.

Implementing statistical learning methods through Bayesian networks. Part 1: a guide to Bayesian parameter estimation using forensic science data

As a thorough aggregation of probability and graph theory, Bayesian networks currently enjoy widespread interest as a means for studying factors that affect the coherent evaluation of scientific evidence in forensic science. Paper I of this series of papers intends to contribute to the discussion of Bayesian networks as a framework that is helpful for both illustrating and implementing statistical procedures that are commonly employed for the study of uncertainties (e.g. the estimation of unknown quantities). While the respective statistical procedures are widely described in literature, the primary aim of this paper is to offer an essentially non-technical introduction on how interested readers may use these analytical approaches - with the help of Bayesian networks - for processing their own forensic science data. Attention is mainly drawn to the structure and underlying rationale of a series of basic and context-independent network fragments that users may incorporate as building blocs while constructing larger inference models. As an example of how this may be done, the proposed concepts will be used in a second paper (Part II) for specifying graphical probability networks whose purpose is to assist forensic scientists in the evaluation of scientific evidence encountered in the context of forensic document examination (i.e. results of the analysis of black toners present on printed or copied documents).

An Open Source, DDI-based Curation System for Social Science Data

Poster at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

Supporting the creation, management, and long-term preservation of social science research data

Poster at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

A rose is a rose is a rose? Defining significant properties of social science research data

Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

Compositions in life science data

The aim of this talk is to convince the reader that there are a lot of interesting statistical problems in presentday life science data analysis which seem ultimately connected with compositional statistics. Key words: SAGE, cDNA microarrays, (1D-)NMR, virus quasispecies