3,697 research outputs found
Fairness-aware Machine Learning in Educational Data Mining
Fairness is an essential requirement of every educational system, which is reflected in a variety of educational activities. With the extensive use of Artificial Intelligence (AI) and Machine Learning (ML) techniques in education, researchers and educators can analyze educational (big) data and propose new (technical) methods in order to support teachers, students, or administrators of (online) learning systems in the organization of teaching and learning. Educational data mining (EDM) is the result of the application and development of data mining (DM), and ML techniques to deal with educational problems, such as student performance prediction and student grouping. However, ML-based decisions in education can be based on protected attributes, such as race or gender, leading to discrimination of individual students or subgroups of students. Therefore, ensuring fairness in ML models also contributes to equity in educational systems. On the other hand, bias can also appear in the data obtained from learning environments. Hence, bias-aware exploratory educational data analysis is important to support unbiased decision-making in EDM.
In this thesis, we address the aforementioned issues and propose methods that mitigate discriminatory outcomes of ML algorithms in EDM tasks. Specifically, we make the following contributions:
We perform bias-aware exploratory analysis of educational datasets using Bayesian networks to identify the relationships among attributes in order to understand bias in the datasets. We focus the exploratory data analysis on features having a direct or indirect relationship with the protected attributes w.r.t. prediction outcomes.
We perform a comprehensive evaluation of the sufficiency of various group fairness measures in predictive models for student performance prediction problems. A variety of experiments on various educational datasets with different fairness measures are performed to provide users with a broad view of unfairness from diverse aspects.
We deal with the student grouping problem in collaborative learning. We introduce the fair-capacitated clustering problem that takes into account cluster fairness and cluster cardinalities. We propose two approaches, namely hierarchical clustering and partitioning-based clustering, to obtain fair-capacitated clustering.
We introduce the multi-fair capacitated (MFC) students-topics grouping problem that satisfies students' preferences while ensuring balanced group cardinalities and maximizing the diversity of members regarding the protected attribute. We propose three approaches: a greedy heuristic approach, a knapsack-based approach using vanilla maximal 0-1 knapsack formulation, and an MFC knapsack approach based on group fairness knapsack formulation.
In short, the findings described in this thesis demonstrate the importance of fairness-aware ML in educational settings. We show that bias-aware data analysis, fairness measures, and fairness-aware ML models are essential aspects to ensure fairness in EDM and the educational environment.Ministry of Science and Culture of Lower Saxony/LernMINT/51410078/E
Logic mining with hybridized 3-satisfiability fuzzy logic and harmony search algorithm in Hopfield neural network for Covid-19 death cases
Since the beginning of the Covid-19 infections in December 2019, the virus has emerged as the most lethally contagious in world history. In this study, the Hopfield neural network and logic mining technique merged to extract data from a model to provide insight into the link between factors influencing the Covid-19 datasets. The suggested technique uses a 3-satisfiability-based reverse analysis (3SATRA) and a hybridized Hopfield neural network to identify the relationships relating to the variables in a set of Covid-19 data. The list of data is to identify the relationships between the key characteristics that lead to a more prolonged time of death of the patients. The learning phase of the hybridized 3-satisfiability (3SAT) Hopfield neural network and the reverse analysis (RA) method has been optimized using a new method of fuzzy logic and two metaheuristic algorithms: Genetic and harmony search algorithms. The performance assessment metrics, such as energy analysis, error analysis, computational time, and accuracy, were computed at the end of the algorithms. The multiple performance metrics demonstrated that the 3SATRA with the fuzzy logic metaheuristic algorithm model outperforms other logic mining models. Furthermore, the experimental findings have demonstrated that the best-induced logic identifies important variables to detect critical patients that need more attention. In conclusion, the results validate the efficiency of the suggested approach, which occurs from the fact that the new version has a positive effect
Exploration autonome et efficiente de chantiers miniers souterrains inconnus avec un drone filaire
Abstract: Underground mining stopes are often mapped using a sensor located at the end of a pole that the operator introduces into the stope from a secure area. The sensor emits laser beams that provide the distance to a detected wall, thus creating a 3D map. This produces shadow zones and a low point density on the distant walls. To address these challenges, a research team from the Université de Sherbrooke is designing a tethered drone equipped with a rotating LiDAR for this mission, thus benefiting from several points of view. The wired transmission allows for unlimited flight time, shared computing, and real-time communication. For compatibility with the movement of the drone after tether entanglements, the excess length is integrated into an onboard spool, contributing to the drone payload. During manual piloting, the human factor causes problems in the perception and comprehension of a virtual 3D environment, as well as the execution of an optimal mission. This thesis focuses on autonomous navigation in two aspects: path planning and exploration. The system must compute a trajectory that maps the entire environment, minimizing the mission time and respecting the maximum onboard tether length. Path planning using a Rapidly-exploring Random Tree (RRT) quickly finds a feasible path, but the optimization is computationally expensive and the performance is variable and unpredictable. Exploration by the frontier method is representative of the space to be explored and the path can be optimized by solving a Traveling Salesman Problem (TSP) but existing techniques for a tethered drone only consider the 2D case and do not optimize the global path. To meet these challenges, this thesis presents two new algorithms. The first one, RRT-Rope, produces an equal or shorter path than existing algorithms in a significantly shorter computation time, up to 70% faster than the next best algorithm in a representative environment. A modified version of RRT-connect computes a feasible path, shortened with a deterministic technique that takes advantage of previously added intermediate nodes. The second algorithm, TAPE, is the first 3D cavity exploration method that focuses on minimizing mission time and unwound tether length. On average, the overall path is 4% longer than the method that solves the TSP, but the tether remains under the allowed length in 100% of the simulated cases, compared to 53% with the initial method. The approach uses a 2-level hierarchical architecture: global planning solves a TSP after frontier extraction, and local planning minimizes the path cost and tether length via a decision function. The integration of these two tools in the NetherDrone produces an intelligent system for autonomous exploration, with semi-autonomous features for operator interaction. This work opens the door to new navigation approaches in the field of inspection, mapping, and Search and Rescue missions.La cartographie des chantiers miniers souterrains est souvent réalisée à l’aide d’un capteur situé au bout d’une perche que l’opérateur introduit dans le chantier, depuis une zone sécurisée. Le capteur émet des faisceaux laser qui fournissent la distance à un mur détecté, créant ainsi une carte en 3D. Ceci produit des zones d’ombres et une faible densité de points sur les parois éloignées. Pour relever ces défis, une équipe de recherche de l’Université de Sherbrooke conçoit un drone filaire équipé d’un LiDAR rotatif pour cette mission, bénéficiant ainsi de plusieurs points de vue. La transmission filaire permet un temps de vol illimité, un partage de calcul et une communication en temps réel. Pour une compatibilité avec le mouvement du drone lors des coincements du fil, la longueur excédante est intégrée dans une bobine embarquée, qui contribue à la charge utile du drone. Lors d’un pilotage manuel, le facteur humain entraîne des problèmes de perception et compréhension d’un environnement 3D virtuel, et d’exécution d’une mission optimale. Cette thèse se concentre sur la navigation autonome sous deux aspects : la planification de trajectoire et l’exploration. Le système doit calculer une trajectoire qui cartographie l’environnement complet, en minimisant le temps de mission et en respectant la longueur maximale de fil embarquée. La planification de trajectoire à l’aide d’un Rapidly-exploring Random Tree (RRT) trouve rapidement un chemin réalisable, mais l’optimisation est coûteuse en calcul et la performance est variable et imprévisible. L’exploration par la méthode des frontières est représentative de l’espace à explorer et le chemin peut être optimisé en résolvant un Traveling Salesman Problem (TSP), mais les techniques existantes pour un drone filaire ne considèrent que le cas 2D et n’optimisent pas le chemin global. Pour relever ces défis, cette thèse présente deux nouveaux algorithmes. Le premier, RRT-Rope, produit un chemin égal ou plus court que les algorithmes existants en un temps de calcul jusqu’à 70% plus court que le deuxième meilleur algorithme dans un environnement représentatif. Une version modifiée de RRT-connect calcule un chemin réalisable, raccourci avec une technique déterministe qui tire profit des noeuds intermédiaires préalablement ajoutés. Le deuxième algorithme, TAPE, est la première méthode d’exploration de cavités en 3D qui minimise le temps de mission et la longueur du fil déroulé. En moyenne, le trajet global est 4% plus long que la méthode qui résout le TSP, mais le fil reste sous la longueur autorisée dans 100% des cas simulés, contre 53% avec la méthode initiale. L’approche utilise une architecture hiérarchique à 2 niveaux : la planification globale résout un TSP après extraction des frontières, et la planification locale minimise le coût du chemin et la longueur de fil via une fonction de décision. L’intégration de ces deux outils dans le NetherDrone produit un système intelligent pour l’exploration autonome, doté de fonctionnalités semi-autonomes pour une interaction avec l’opérateur. Les travaux réalisés ouvrent la porte à de nouvelles approches de navigation dans le domaine des missions d’inspection, de cartographie et de recherche et sauvetage
Design of new algorithms for gene network reconstruction applied to in silico modeling of biomedical data
Programa de Doctorado en Biotecnología, Ingeniería y Tecnología QuímicaLínea de Investigación: Ingeniería, Ciencia de Datos y BioinformáticaClave Programa: DBICódigo Línea: 111The root causes of disease are still poorly understood. The success of current therapies is limited because persistent diseases are frequently treated based on their symptoms rather than the underlying cause of the disease. Therefore, biomedical research is experiencing a technology-driven shift to data-driven holistic approaches to better characterize the molecular mechanisms causing disease. Using omics data as an input, emerging disciplines like network biology attempt to model the relationships between biomolecules. To this effect, gene co- expression networks arise as a promising tool for deciphering the relationships between genes in large transcriptomic datasets. However, because of their low specificity and high false positive rate, they demonstrate a limited capacity to retrieve the disrupted mechanisms that lead to disease onset, progression, and maintenance. Within the context of statistical modeling, we dove deeper into the reconstruction of gene co-expression networks with the specific goal of discovering disease-specific features directly from expression data. Using ensemble techniques, which combine the results of various metrics, we were able to more precisely capture biologically significant relationships between genes. We were able to find de novo potential disease-specific features with the help of prior biological knowledge and the development of new network inference techniques.
Through our different approaches, we analyzed large gene sets across multiple samples and used gene expression as a surrogate marker for the inherent biological processes, reconstructing robust gene co-expression networks that are simple to explore. By mining disease-specific gene co-expression networks we come up with a useful framework for identifying new omics-phenotype associations from conditional expression datasets.In this sense, understanding diseases from the perspective of biological network perturbations will improve personalized medicine, impacting rational biomarker discovery, patient stratification and drug design, and ultimately leading to more targeted therapies.Universidad Pablo de Olavide de Sevilla. Departamento de Deporte e Informátic
Less is More: Restricted Representations for Better Interpretability and Generalizability
Deep neural networks are prevalent in supervised learning for large amounts of tasks such as image classification, machine translation and even scientific discovery.
Their success is often at the sacrifice of interpretability and generalizability. The increasing complexity of models and involvement of the pre-training process make the inexplicability more imminent. The outstanding performance when labeled data are abundant while prone to overfit when labeled data are limited demonstrates the difficulty of deep neural networks' generalizability to different datasets.
This thesis aims to improve interpretability and generalizability by restricting representations. We choose to approach interpretability by focusing on attribution analysis to understand which features contribute to prediction on BERT, and to approach generalizability by focusing on effective methods in a low-data regime.
We consider two strategies of restricting representations: (1) adding bottleneck, and (2) introducing compression. Given input x, suppose we want to learn y with the latent representation z (i.e. x→z→y), adding bottleneck means adding function R such that L(R(z)) < L(z) and introducing compression means adding function R so that L(R(y)) < L(y) where L refers to the number of bits. In other words, the restriction is added either in the middle of the pipeline or at the end of it.
We first introduce how adding information bottleneck can help attribution analysis and apply it to investigate BERT's behavior on text classification in Chapter 3.
We then extend this attribution method to analyze passage reranking in Chapter 4, where we conduct a detailed analysis to understand cross-layer and cross-passage behavior.
Adding bottleneck can not only provide insight to understand deep neural networks but can also be used to increase generalizability.
In Chapter 5, we demonstrate the equivalence between adding bottleneck and doing neural compression. We then leverage this finding with a framework called Non-Parametric learning by Compression with Latent Variables (NPC-LV), and show how optimizing neural compressors can be used in the non-parametric image classification with few labeled data.
To further investigate how compression alone helps non-parametric learning without latent variables (NPC), we carry out experiments with a universal compressor gzip on text classification in Chapter 6.
In Chapter 7, we elucidate methods of adopting the perspective of doing compression but without the actual process of compression using T5.
Using experimental results in passage reranking, we show that our method is highly effective in a low-data regime when only one thousand query-passage pairs are available.
In addition to the weakly supervised scenario, we also extend our method to large language models like GPT under almost no supervision --- in one-shot and zero-shot settings. The experiments show that without extra parameters or in-context learning, GPT can be used for semantic similarity, text classification, and text ranking and outperform strong baselines, which is presented in Chapter 8.
The thesis proposes to tackle two big challenges in machine learning --- "interpretability" and "generalizability" through restricting representation. We provide both theoretical derivation and empirical results to show the effectiveness of using information-theoretic approaches. We not only design new algorithms but also provide numerous insights on why and how "compression" is so important in understanding deep neural networks and improving generalizability
Recommended Implementation of Quantitative Susceptibility Mapping for Clinical Research in The Brain: A Consensus of the ISMRM Electro-Magnetic Tissue Properties Study Group
This article provides recommendations for implementing quantitative susceptibility mapping (QSM) for clinical brain research. It is a consensus of the ISMRM Electro-Magnetic Tissue Properties Study Group. While QSM technical development continues to advance rapidly, the current QSM methods have been demonstrated to be repeatable and reproducible for generating quantitative tissue magnetic susceptibility maps in the brain. However, the many QSM approaches available give rise to the need in the neuroimaging community for guidelines on implementation. This article describes relevant considerations and provides specific implementation recommendations for all steps in QSM data acquisition, processing, analysis, and presentation in scientific publications. We recommend that data be acquired using a monopolar 3D multi-echo GRE sequence, that phase images be saved and exported in DICOM format and unwrapped using an exact unwrapping approach. Multi-echo images should be combined before background removal, and a brain mask created using a brain extraction tool with the incorporation of phase-quality-based masking. Background fields should be removed within the brain mask using a technique based on SHARP or PDF, and the optimization approach to dipole inversion should be employed with a sparsity-based regularization. Susceptibility values should be measured relative to a specified reference, including the common reference region of whole brain as a region of interest in the analysis, and QSM results should be reported with - as a minimum - the acquisition and processing specifications listed in the last section of the article. These recommendations should facilitate clinical QSM research and lead to increased harmonization in data acquisition, analysis, and reporting
Advances and Applications of DSmT for Information Fusion. Collected Works, Volume 5
This fifth volume on Advances and Applications of DSmT for Information Fusion collects theoretical and applied contributions of researchers working in different fields of applications and in mathematics, and is available in open-access. The collected contributions of this volume have either been published or presented after disseminating the fourth volume in 2015 in international conferences, seminars, workshops and journals, or they are new. The contributions of each part of this volume are chronologically ordered.
First Part of this book presents some theoretical advances on DSmT, dealing mainly with modified Proportional Conflict Redistribution Rules (PCR) of combination with degree of intersection, coarsening techniques, interval calculus for PCR thanks to set inversion via interval analysis (SIVIA), rough set classifiers, canonical decomposition of dichotomous belief functions, fast PCR fusion, fast inter-criteria analysis with PCR, and improved PCR5 and PCR6 rules preserving the (quasi-)neutrality of (quasi-)vacuous belief assignment in the fusion of sources of evidence with their Matlab codes.
Because more applications of DSmT have emerged in the past years since the apparition of the fourth book of DSmT in 2015, the second part of this volume is about selected applications of DSmT mainly in building change detection, object recognition, quality of data association in tracking, perception in robotics, risk assessment for torrent protection and multi-criteria decision-making, multi-modal image fusion, coarsening techniques, recommender system, levee characterization and assessment, human heading perception, trust assessment, robotics, biometrics, failure detection, GPS systems, inter-criteria analysis, group decision, human activity recognition, storm prediction, data association for autonomous vehicles, identification of maritime vessels, fusion of support vector machines (SVM), Silx-Furtif RUST code library for information fusion including PCR rules, and network for ship classification.
Finally, the third part presents interesting contributions related to belief functions in general published or presented along the years since 2015. These contributions are related with decision-making under uncertainty, belief approximations, probability transformations, new distances between belief functions, non-classical multi-criteria decision-making problems with belief functions, generalization of Bayes theorem, image processing, data association, entropy and cross-entropy measures, fuzzy evidence numbers, negator of belief mass, human activity recognition, information fusion for breast cancer therapy, imbalanced data classification, and hybrid techniques mixing deep learning with belief functions as well
Leveraging elasticity theory to calculate cell forces: From analytical insights to machine learning
Living cells possess capabilities to detect and respond to mechanical features of their surroundings. In traction force microscopy, the traction of cells on an elastic substrate is made visible by observing substrate deformation as measured by the movement of embedded marker beads. Describing the substrates by means of elasticity theory, we can calculate the adhesive forces, improving our understanding of cellular function and behavior. In this dissertation, I combine analytical solutions with numerical methods and machine learning techniques to improve traction prediction in a range of experimental applications. I describe how to include the normal traction component in regularization-based Fourier approaches, which I apply to experimental data. I compare the dominant strategies for traction reconstruction, the direct method and inverse, regularization-based approaches and find, that the latter are more precise while the former is more stress resilient to noise. I find that a point-force based reconstruction can be used to study the force balance evolution in response to microneedle pulling showing a transition from a dipolar into a monopolar force arrangement. Finally, I show how a conditional invertible neural network not only reconstructs adhesive areas more localized, but also reveals spatial correlations and variations in reliability of traction reconstructions
Uncertainty Quantification in Machine Learning for Engineering Design and Health Prognostics: A Tutorial
On top of machine learning models, uncertainty quantification (UQ) functions
as an essential layer of safety assurance that could lead to more principled
decision making by enabling sound risk assessment and management. The safety
and reliability improvement of ML models empowered by UQ has the potential to
significantly facilitate the broad adoption of ML solutions in high-stakes
decision settings, such as healthcare, manufacturing, and aviation, to name a
few. In this tutorial, we aim to provide a holistic lens on emerging UQ methods
for ML models with a particular focus on neural networks and the applications
of these UQ methods in tackling engineering design as well as prognostics and
health management problems. Toward this goal, we start with a comprehensive
classification of uncertainty types, sources, and causes pertaining to UQ of ML
models. Next, we provide a tutorial-style description of several
state-of-the-art UQ methods: Gaussian process regression, Bayesian neural
network, neural network ensemble, and deterministic UQ methods focusing on
spectral-normalized neural Gaussian process. Established upon the mathematical
formulations, we subsequently examine the soundness of these UQ methods
quantitatively and qualitatively (by a toy regression example) to examine their
strengths and shortcomings from different dimensions. Then, we review
quantitative metrics commonly used to assess the quality of predictive
uncertainty in classification and regression problems. Afterward, we discuss
the increasingly important role of UQ of ML models in solving challenging
problems in engineering design and health prognostics. Two case studies with
source codes available on GitHub are used to demonstrate these UQ methods and
compare their performance in the life prediction of lithium-ion batteries at
the early stage and the remaining useful life prediction of turbofan engines
Comparative genomics of recent adaptation in Candida pathogens
[eng] Fungal infections pose a serious health threat, affecting >1,000 million people and causing ~1.5 million deaths each year. The problem is growing due to insufficient diagnostic and therapeutic options, increased number of susceptible patients, expansion of pathogens partly linked to climate change and the rise of antifungal drug resistance. Among other fungal pathogens, Candida species are a major cause of severe hospital-acquired infections, with high mortality in immunocompromised patients. Various Candida pathogens constitute a public health issue, which require further efforts to develop new drugs, optimize currently available treatments and improve diagnostics. Given the high dynamism of Candida genomes, a promising strategy to improve current therapies and diagnostics is to understand the evolutionary mechanisms of adaptation to antifungal drugs and to the human host. Previous work using in vitro evolution, population genomics, selection inferences and Genome Wide Association Studies (GWAS) have partially clarified such recent adaptation, but various open questions remain. In the three research articles that conform this PhD thesis we addressed some of these gaps from the perspective of comparative genomics.
First, we addressed methodological issues regarding the analysis of Candida genomes. Studying recent adaptation in these pathogens requires adequate bioinformatic tools for variant calling, filtering and functional annotation. Among other reasons, current methods are suboptimal due to limited accuracy to identify structural variants from short read sequencing data. In addition, there is a need for easy-to-use, reproducible variant calling pipelines. To address these gaps we developed the “personalized Structural Variation detection” pipeline (perSVade), a framework to call, filter and annotate several variant types, including structural variants, directly from reads. PerSVade enables accurate identification of structural variants in any species of interest, such as Candida pathogens. In addition, our tool automatically predicts the structural variant calling accuracy on simulated genomes, which informs about the reliability of the calling process. Furthermore, perSVade can be used to analyze single nucleotide polymorphisms and copy number-variants, so that it facilitates multi-variant, reproducible genomic studies. This tool will likely boost variant analyses in Candida pathogens and beyond.
Second, we addressed open questions about recent adaptation in Candida, using perSVade for variant identification. On the one hand, we investigated the evolutionary mechanisms of drug resistance in Candida glabrata. For this, we used a large-scale in vitro evolution experiment to study adaptation to two commonly-used antifungals: fluconazole and anidulafungin. Our results show rapid adaptation to one or both drugs, with moderate fitness costs and through few mutations in a narrow set of genes. In addition, we characterize a novel role of ERG3 mutations in cross-resistance towards fluconazole in
anidulafungin-adapted strains. These findings illuminate the mutational paths leading to drug resistance and cross-resistance in Candida pathogens. On the other hand, we reanalyzed ~2,000 public genomes and phenotypes to understand the signs of recent selection and drug resistance in six major Candida species: C. auris, C. glabrata, C. albicans, C. tropicalis, C. parapsilosis and C. orthopsilosis. We found hundreds of genes under recent selection, suggesting that clinical adaptation is diverse and complex. These involve species-specific but also convergently affected processes, such as cell adhesion, which could underlie conserved adaptive mechanisms. In addition, using GWAS we predicted known drivers of antifungal resistance alongside potentially novel players. Furthermore, our analyses reveal an important role of generally-overlooked structural variants, and suggest an unexpected involvement of (para)sexual recombination in the spread of resistance. Taken together, our findings provide novel insights on how Candida pathogens adapt to human-related environments and suggest candidate genes that deserve future attention. In summary, the results of this thesis improve our knowledge about the mechanisms of recent adaptation in Candida pathogens, which may enable improved therapeutic and diagnostic applications.[cat] Les infeccions fúngiques representen una greu amenaça per a la salut, afectant a més de 1.000 milions de persones i causant aproximadament 1,5 milions de morts cada any. El problema està augmentant a causa d’unes opcions terapèutiques i diagnòstiques insuficients, l'increment del nombre de pacients susceptibles, l'expansió dels patògens parcialment vinculada al canvi climàtic i l'augment de la resistència als fàrmacs antifúngics. D’entre diversos fongs patògens, els llevats del gènere Candida són una causa important d'infeccions nosocomials, amb una alta mortalitat en pacients immunodeprimits. Diverses espècies de Candida constitueixen un problema de salut pública, cosa que requereix més esforços per a desenvolupar nous medicaments, optimitzar els tractaments disponibles i millorar els diagnòstics. Tenint en compte el dinamisme genòmic d’aquests patògens, una estratègia prometedora per millorar les teràpies i diagnòstics actuals és comprendre els mecanismes evolutius d'adaptació als fàrmacs antifúngics i a l’hoste humà. Treballs anteriors utilitzant l'evolució in vitro, la genòmica de poblacions, les inferències de selecció i els estudis d'associació de genoma complet (GWAS, per les sigles en anglès) han aclarit parcialment aquesta adaptació recent, però encara hi ha diverses preguntes obertes. En els tres articles que conformen aquesta tesi doctoral, hem abordat algunes d'aquestes preguntes des de la perspectiva de la genòmica comparativa.
En primer lloc, hem abordat qüestions metodològiques relatives a l'anàlisi dels genomes de les espècies Candida. L'estudi de l'adaptació recent en aquests patògens requereix eines bioinformàtiques adequades per a la detecció, filtratge i anotació funcional de variants genètiques. Entre altres raons, els mètodes actuals són subòptims a causa de la limitada precisió per identificar variants estructurals a partir de dades de seqüenciació amb lectures curtes. A més, hi ha una necessitat d’eines computacionals per a la detecció de variants que siguin senzilles d'utilitzar i reproduibles. Per abordar aquestes mancances, hem desenvolupat el mètode bioinformàtic "personalized Structural Variation detection" (perSVade), una eina que permet la detecció, filtratge i anotació de diversos tipus de variants, incloent-hi les variants estructurals, directament des de les lectures. PerSVade permet la identificació precisa de les variants estructurals en qualsevol espècie d'interès, com ara els patògens Candida. A més, la nostra eina prediu automàticament la precisió de la detecció d’aquestes variants en genomes simulats, la qual cosa informa sobre la fiabilitat del procés. Finalment, perSVade es pot utilitzar per analitzar altres tipus de variants, com els polimorfismes de nucleòtid únic o els canvis en el nombre de còpies, facilitant així estudis genòmics integrals i reproduibles. Aquesta eina probablement impulsarà les anàlisis genòmiques en els patògens Candida i també en altres espècies.
En segon lloc, hem abordat algunes de les preguntes obertes sobre l'adaptació recent en els llevats Candida, utilitzant perSVade per a la identificació de variants. D'una banda, hem investigat els mecanismes evolutius de resistència als fàrmacs antifúngics en Candida glabrata. Per a això, hem utilitzat un experiment
d'evolució in vitro a gran escala per estudiar l'adaptació a dos antifúngics comuns: el fluconazol i l’anidulafungina. Els nostres resultats mostren una adaptació ràpida a un o ambdós fàrmacs, amb un cost per al creixement moderat i a través de poques mutacions en un nombre reduït de gens. A més, hem caracteritzat un paper nou de les mutacions en ERG3 en la resistència creuada al fluconazol en soques adaptades a anidulafungina. Aquests descobriments aclareixen els processos mutacionals que condueixen a la resistència als fàrmacs i a la resistència creuada en els patògens Candida. D'altra banda, hem re-analitzat aproximadament 2.000 genomes i fenotips disponibles en repositoris públics per a comprendre els senyals genòmics de selecció recent i de resistència a fàrmacs antifúngics, en sis espècies rellevants de Candida: C. auris, C. glabrata, C. albicans, C. tropicalis, C. parapsilosis i C. orthopsilosis. Hem trobat centenars de gens sota selecció recent, suggerint que l'adaptació clínica és diversa i complexa. Aquests gens estan relacionats amb funcions específiques de cada espècie, però també trobem processos alterats de manera similar en diferents patògens, com per exemple l’adhesió cel·lular, cosa que indica fenòmens d’adaptació conservats. A part, utilitzant GWAS hem predit mecanismes esperats de resistència a antifúngics i també possibles nous factors. A més, les nostres anàlisis revelen un paper important de les variants estructurals, generalment poc estudiades, i suggereixen una implicació inesperada de la recombinació (para)sexual en la propagació de la resistència. En conjunt, els nostres descobriments proporcionen noves perspectives sobre com els patògens Candida s'adapten als entorns humans, i suggereixen gens candidats que mereixen investigacions futures. En resum, els resultats d’aquesta tesi milloren el nostre coneixement sobre els mecanismes d'adaptació recent en els patògens Candida, cosa que pot permetre el disseny de noves teràpies i diagnòstics
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