41 research outputs found

    LIPIcs, Volume 251, ITCS 2023, Complete Volume

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    LIPIcs, Volume 251, ITCS 2023, Complete Volum

    LIPIcs, Volume 261, ICALP 2023, Complete Volume

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    LIPIcs, Volume 261, ICALP 2023, Complete Volum

    Network-based methods for biological data integration in precision medicine

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    [eng] The vast and continuously increasing volume of available biomedical data produced during the last decades opens new opportunities for large-scale modeling of disease biology, facilitating a more comprehensive and integrative understanding of its processes. Nevertheless, this type of modelling requires highly efficient computational systems capable of dealing with such levels of data volumes. Computational approximations commonly used in machine learning and data analysis, namely dimensionality reduction and network-based approaches, have been developed with the goal of effectively integrating biomedical data. Among these methods, network-based machine learning stands out due to its major advantage in terms of biomedical interpretability. These methodologies provide a highly intuitive framework for the integration and modelling of biological processes. This PhD thesis aims to explore the potential of integration of complementary available biomedical knowledge with patient-specific data to provide novel computational approaches to solve biomedical scenarios characterized by data scarcity. The primary focus is on studying how high-order graph analysis (i.e., community detection in multiplex and multilayer networks) may help elucidate the interplay of different types of data in contexts where statistical power is heavily impacted by small sample sizes, such as rare diseases and precision oncology. The central focus of this thesis is to illustrate how network biology, among the several data integration approaches with the potential to achieve this task, can play a pivotal role in addressing this challenge provided its advantages in molecular interpretability. Through its insights and methodologies, it introduces how network biology, and in particular, models based on multilayer networks, facilitates bringing the vision of precision medicine to these complex scenarios, providing a natural approach for the discovery of new biomedical relationships that overcomes the difficulties for the study of cohorts presenting limited sample sizes (data-scarce scenarios). Delving into the potential of current artificial intelligence (AI) and network biology applications to address data granularity issues in the precision medicine field, this PhD thesis presents pivotal research works, based on multilayer networks, for the analysis of two rare disease scenarios with specific data granularities, effectively overcoming the classical constraints hindering rare disease and precision oncology research. The first research article presents a personalized medicine study of the molecular determinants of severity in congenital myasthenic syndromes (CMS), a group of rare disorders of the neuromuscular junction (NMJ). The analysis of severity in rare diseases, despite its importance, is typically neglected due to data availability. In this study, modelling of biomedical knowledge via multilayer networks allowed understanding the functional implications of individual mutations in the cohort under study, as well as their relationships with the causal mutations of the disease and the different levels of severity observed. Moreover, the study presents experimental evidence of the role of a previously unsuspected gene in NMJ activity, validating the hypothetical role predicted using the newly introduced methodologies. The second research article focuses on the applicability of multilayer networks for gene priorization. Enhancing concepts for the analysis of different data granularities firstly introduced in the previous article, the presented research provides a methodology based on the persistency of network community structures in a range of modularity resolution, effectively providing a new framework for gene priorization for patient stratification. In summary, this PhD thesis presents major advances on the use of multilayer network-based approaches for the application of precision medicine to data-scarce scenarios, exploring the potential of integrating extensive available biomedical knowledge with patient-specific data

    Exploration of Chemical Space: Formal, chemical and historical aspects

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    Starting from the observation that substances and reactions are the central entities of chemistry, I have structured chemical knowledge into a formal space called a directed hypergraph, which arises when substances are connected by their reactions. I call this hypernet chemical space. In this thesis, I explore different levels of description of this space: its evolution over time, its curvature, and categorical models of its compositionality. The vast majority of the chemical literature focuses on investigations of particular aspects of some substances or reactions, which have been systematically recorded in comprehensive databases such as Reaxys for the last 200 years. While complexity science has made important advances in physics, biology, economics, and many other fields, it has somewhat neglected chemistry. In this work, I propose to take a global view of chemistry and to combine complexity science tools, modern data analysis techniques, and geometric and compositional theories to explore chemical space. This provides a novel view of chemistry, its history, and its current status. We argue that a large directed hypergraph, that is, a model of directed relations between sets, underlies chemical space and that a systematic study of this structure is a major challenge for chemistry. Using the Reaxys database as a proxy for chemical space, we search for large-scale changes in a directed hypergraph model of chemical knowledge and present a data-driven approach to navigate through its history and evolution. These investigations focus on the mechanistic features by which this space has been expanding: the role of synthesis and extraction in the production of new substances, patterns in the selection of starting materials, and the frequency with which reactions reach new regions of chemical space. Large-scale patterns that emerged in the last two centuries of chemical history are detected, in particular, in the growth of chemical knowledge, the use of reagents, and the synthesis of products, which reveal both conservatism and sharp transitions in the exploration of the space. Furthermore, since chemical similarity of substances arises from affinity patterns in chemical reactions, we quantify the impact of changes in the diversity of the space on the formulation of the system of chemical elements. In addition, we develop formal tools to probe the local geometry of the resulting directed hypergraph and introduce the Forman-Ricci curvature for directed and undirected hypergraphs. This notion of curvature is characterized by applying it to social and chemical networks with higher order interactions, and then used for the investigation of the structure and dynamics of chemical space. The network model of chemistry is strongly motivated by the observation that the compositional nature of chemical reactions must be captured in order to build a model of chemical reasoning. A step forward towards categorical chemistry, that is, a formalization of all the flavors of compositionality in chemistry, is taken by the construction of a categorical model of directed hypergraphs. We lifted the structure from a lineale (a poset version of a symmetric monoidal closed category) to a category of Petri nets, whose wiring is a bipartite directed graph equivalent to a directed hypergraph. The resulting construction, based on the Dialectica categories introduced by Valeria De Paiva, is a symmetric monoidal closed category with finite products and coproducts, which provides a formal way of composing smaller networks into larger in such a way that the algebraic properties of the components are preserved in the resulting network. Several sets of labels, often used in empirical data modeling, can be given the structure of a lineale, including: stoichiometric coefficients in chemical reaction networks, reaction rates, inhibitor arcs, Boolean interactions, unknown or incomplete data, and probabilities. Therefore, a wide range of empirical data types for chemical substances and reactions can be included in our model

    EUROCOMB 21 Book of extended abstracts

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    r-Simple k-Path and Related Problems Parameterized by k/r

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    Combining task and motion planning for mobile manipulators

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    Aplicat embargament des de la data de defensa fins el dia 31/12/2019Premi Extraordinari de Doctorat, promoció 2018-2019. Àmbit d’Enginyeria IndustrialThis thesis addresses the combination of task and motion planning which deals with different types of robotic manipulation problems. Manipulation problems are referred to as mobile manipulation, collaborative multiple mobile robots tasks, and even higher dimensional tasks (like bi-manual robots or mobile manipulators). Task and motion planning problems needs to obtain a geometrically feasible manipulation plan through symbolic and geometric search space. The combination of task and motion planning levels has emerged as a challenging issue as the failure leads robots to dead-end tasks due to geometric constraints. In addition, task planning is combined with physics-based motion planning and information to cope with manipulation tasks in which interactions between robots and objects are required, or also a low-cost feasible plan in terms of power is looked for. Moreover, combining task and motion planning frameworks is enriched by introducing manipulation knowledge. It facilitates the planning process and aids to provide the way of executing symbolic actions. Combining task and motion planning can be considered under uncertain information and with human-interaction. Uncertainty can be viewed in the initial state of the robot world or the result of symbolic actions. To deal with such issues, contingent-based task and motion planning is proposed using a perception system and human knowledge. Also, robots can ask human for those tasks which are difficult or infeasible for the purpose of collaboration. An implementation framework to combine different types of task and motion planning is presented. All the required modules and tools are also illustrated. As some task planning algorithms are implemented in Prolog or C++ languages and our geometric reasoner is developed in C++, the flow of information between different languages is explained.Aquesta tesis es centra en les eines de planificació combinada a nivell de tasca i a nivell de moviments per abordar diferents problemes de manipulació robòtica. Els problemes considerats són de navegació de robots mòbil enmig de obstacles no fixes, tasques de manipulació cooperativa entre varis robots mòbils, i tasques de manipulació de dimensió més elevada com les portades a terme amb robots bi-braç o manipuladors mòbils. La planificació combinada de tasques i de moviments ha de cercar un pla de manipulació que sigui geomètricament realitzable, a través de d'un espai de cerca simbòlic i geomètric. La combinació dels nivells de planificació de tasca i de moviments ha sorgit com un repte ja que les fallades degudes a les restriccions geomètriques poden portar a tasques sense solució. Addicionalment, la planificació a nivell de tasca es combina amb informació de la física de l'entorn i amb mètodes de planificació basats en la física, per abordar tasques de manipulació en les que la interacció entre el robot i els objectes és necessària, o també si es busca un pla realitzable i amb un baix cost en termes de potència. A més, el marc proposat per al combinació de la planificació a nivell de tasca i a nivell de moviments es millora mitjançant l'ús de coneixement, que facilita el procés de planificació i ajuda a trobar la forma d'executar accions simbòliques. La combinació de nivells de planificació també es pot considerar en casos d'informació incompleta i en la interacció humà-robot. La incertesa es considera en l'estat inicial i en el resultat de les accions simbòliques. Per abordar aquest problema, es proposa la planificació basada en contingències usant un sistema de percepció i el coneixement de l'operari humà. Igualment, els robots poden demanar col·laboració a l'operari humà per a que realitzi aquelles accions que són difícils o no realitzables pel robot. Es presenta també un marc d'implementació per a la combinació de nivells de planificació usant diferents mètodes, incloent tots els mòduls i eines necessàries. Com que alguns algorismes estan implementats en Prolog i d'altres en C++, i el mòdul de raonament geomètric proposat està desenvolupat en C++, es detalla el flux d'informació entre diferents llenguatges.Award-winningPostprint (published version

    Asymptotic study of regular planar graphs

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    The central topic of this dissertation is the study of some families of regular planar graphs and maps. We are in particular interested in their asymptotic enumeration in order to understand of the associated uniform random model. In a first part, we give both an exact and an asymptotic enumeration of labelled cubic planar graphs, multigraphs and simple maps, via a recursive scheme following the iterative decompositon of a graph in smaller components of higher connecttivity. In the second part, we apply those results to the study a the uniform random labelled cubic planar graph. We compute for instance the probability of connectivity, and prove that some significant parameters are distributed following a Gaussian limit law: the numbers of cut-vertices, isthmuses, blocks, cherries, near-bricks, and triangles. In the third and last part, we develop the first recursive combinatorial scheme to enumerate 4-regular labelled planar graphs. This scheme is based on a decomposition in terms of connectivity, similar to that of cubic planar graphs, which leads to the exact enumeration of 4-regular planar graphs and simple maps.Das zentrale Thema dieser Dissertation sind Familien von regulären planaren Graphen und Karten. Insbesondere sind wir an daran interessiert, diese zu zählen und die Zusammenhänge zu deren zufälligen Gegenstücken zu erforschen. Im ersten Teil geben wir sowohl eine rekursive als auch eine asymptotische Abzählung von kubischen, planaren Graphen, Multigraphen und einfachen Karten, durch eine Dekomposition entlang deren Komponenten. Im zweiten Teil wenden wir diese Resultate auf zufällige kubische planare Graphen an. Insbesondere berechnen wir die Wahrscheinlichkeit von Zusammenhängigkeit, und beweisen das einige bedeutende Parameter normalverteilt sind: die Anzahl der cut-vertices, isthmuses, Blöcke, cherries, near-bricks und Dreiecke. Im dritten und letzten Teil entwickeln wir das erste kombinatorisches Schema, basierend auf einem Dekompositionsschema das ähnlich zu dem im Kontext von kubischen planaren Graphen ist, das zur rekursiven Abzählung von 4-regulären planaren Graphen und einfachen Karten führt
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