Understanding the Code of Life: Holistic Conceptual Modeling of the Genome

[ES] En las últimas décadas, los avances en la tecnología de secuenciación han producido cantidades significativas de datos genómicos, hecho que ha revolucionado nuestra comprensión de la biología. Sin embargo, la cantidad de datos generados ha superado con creces nuestra capacidad para interpretarlos. Descifrar el código de la vida es un gran reto. A pesar de los numerosos avances realizados, nuestra comprensión del mismo sigue siendo mínima, y apenas estamos empezando a descubrir todo su potencial, por ejemplo, en áreas como la medicina de precisión o la farmacogenómica. El objetivo principal de esta tesis es avanzar en nuestra comprensión de la vida proponiendo una aproximación holística mediante un enfoque basado en modelos que consta de tres artefactos: i) un esquema conceptual del genoma, ii) un método para su aplicación en el mundo real, y iii) el uso de ontologías fundacionales para representar el conocimiento del dominio de una forma más precisa y explícita. Las dos primeras contribuciones se han validado mediante la implementación de sistemas de información genómicos basados en modelos conceptuales. La tercera contribución se ha validado mediante experimentos empíricos que han evaluado si el uso de ontologías fundacionales conduce a una mejor comprensión del dominio genómico. Los artefactos generados ofrecen importantes beneficios. En primer lugar, se han generado procesos de gestión de datos más eficientes, lo que ha permitido mejorar los procesos de extracción de conocimientos. En segundo lugar, se ha logrado una mejor comprensión y comunicación del dominio.[CA] En les últimes dècades, els avanços en la tecnologia de seqüenciació han produït quantitats significatives de dades genòmiques, fet que ha revolucionat la nostra comprensió de la biologia. No obstant això, la quantitat de dades generades ha superat amb escreix la nostra capacitat per a interpretar-los. Desxifrar el codi de la vida és un gran repte. Malgrat els nombrosos avanços realitzats, la nostra comprensió del mateix continua sent mínima, i a penes estem començant a descobrir tot el seu potencial, per exemple, en àrees com la medicina de precisió o la farmacogenómica. L'objectiu principal d'aquesta tesi és avançar en la nostra comprensió de la vida proposant una aproximació holística mitjançant un enfocament basat en models que consta de tres artefactes: i) un esquema conceptual del genoma, ii) un mètode per a la seua aplicació en el món real, i iii) l'ús d'ontologies fundacionals per a representar el coneixement del domini d'una forma més precisa i explícita. Les dues primeres contribucions s'han validat mitjançant la implementació de sistemes d'informació genòmics basats en models conceptuals. La tercera contribució s'ha validat mitjançant experiments empírics que han avaluat si l'ús d'ontologies fundacionals condueix a una millor comprensió del domini genòmic. Els artefactes generats ofereixen importants beneficis. En primer lloc, s'han generat processos de gestió de dades més eficients, la qual cosa ha permés millorar els processos d'extracció de coneixements. En segon lloc, s'ha aconseguit una millor comprensió i comunicació del domini.[EN] Over the last few decades, advances in sequencing technology have produced significant amounts of genomic data, which has revolutionised our understanding of biology. However, the amount of data generated has far exceeded our ability to interpret it. Deciphering the code of life is a grand challenge. Despite our progress, our understanding of it remains minimal, and we are just beginning to uncover its full potential, for instance, in areas such as precision medicine or pharmacogenomics. The main objective of this thesis is to advance our understanding of life by proposing a holistic approach, using a model-based approach, consisting of three artifacts: i) a conceptual schema of the genome, ii) a method for its application in the real-world, and iii) the use of foundational ontologies to represent domain knowledge in a more unambiguous and explicit way. The first two contributions have been validated by implementing genome information systems based on conceptual models. The third contribution has been validated by empirical experiments assessing whether using foundational ontologies leads to a better understanding of the genomic domain. The artifacts generated offer significant benefits. First, more efficient data management processes were produced, leading to better knowledge extraction processes. Second, a better understanding and communication of the domain was achieved.Las fructíferas discusiones y los resultados derivados de los proyectos INNEST2021 /57, MICIN/AEI/10.13039/501100011033, PID2021-123824OB-I00, CIPROM/2021/023 y PDC2021- 121243-I00 han contribuido en gran medida a la calidad final de este tesis.García Simón, A. (2022). Understanding the Code of Life: Holistic Conceptual Modeling of the Genome [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/19143

A Model-Based graphical editor for supporting the creation, verification and validation of OntoUML conceptual models

Essa tese apresenta um editor gráfico baseado em modelos para o suporte à criação, verificação e validação de modelos conceituais e ontologias de domínio em uma linguagem de modelagem filosoficamente e cognitivamente bem-fundada chamada OntoUML. O editor é projetado de forma que, por um lado, ele protege o usuário da complexidade dos princípios ontológicos subjacentes à essa linguagem. Por outro lado, ele reforça esses princípios nos modelos produzidos por prover um mecanismo para verificação formal automática de restrições, daí assegurando que os modelos criados serão sintaticamente corretos. Além disso, avaliar a qualidade de modelos conceituais é um ponto chave para assegurar que modelos conceituais podem ser utilizados efetivamente como uma base para o entendimento, acordo e construção de sistemas de informação. Por essa razão, o editor é também capaz de gerar instâncias de modelos automaticamente por meio da transformação desses modelos em especificações na linguagem, baseada em lógica, chamada Alloy. Como as especificações Alloy geradas incluem os axiomas modais da ontologia fundacional subjacente à OntoUML, chamada Unified Foundational Ontology (UFO), então as instâncias geradas automaticamente vão apresentar um comportamento modal enquanto estiverem sendo classificadas dinamicamente, suportando, assim, a validação das meta-propriedades modais dos tipos fornecidos pela linguagem OntoUML

Representing Dynamic Invariants in Ontologically Well-Founded Conceptual Models

Conceptual models often capture the invariant aspects of the phenomena we perceive. These invariants may be considered static when they refer to structures we perceive in phenomena at a particular point in time or dynamic/temporal when they refer to regularities across different points in time. While static invariants have received significant attention, dynamics enjoy marginal support in widely-employed techniques such as UML and OCL. This thesis aims at addressing this gap by proposing a technique for the representation of dynamic invariants of subject domains in UML-based conceptual models. For that purpose, a temporal extension of OCL is proposed. It enriches the ontologically well-founded OntoUML profile and enables the expression of a variety of (arbitrary) temporal constraints. The extension is fully implemented in the tool for specification, verification and simulation of enriched OntoUML models

A model-driven approach to the conceptual modeling of situations : from specification to validation

A modelagem de situações para aplicações sensíveis ao contexto, também chamadas de aplicações sensíveis a situações, é, por um lado, uma tarefa chave para o funcionamento adequado dessas aplicações. Por outro lado, essa também é uma tafera árdua graças à complexidade e à vasta gama de tipos de situações possíveis. Com o intuito de facilitar a representação desses tipos de situações em tempo de projeto, foi criada a Linguagem de Modelagem de Situações (Situation Modeling Language - SML), a qual se baseia parcialmente em ricas teorias ontológicas de modelagem conceitual, além de fornecer uma plataforma de detecção de situação em tempo de execução. Apesar do benefício da existência dessa infraestrutura, a tarefa de definir tipos de situação é ainda não-trivial, podendo carregar problemas que dificilmente são detectados por modeladores via inspeções manuais. Esta dissertação tem o propósito de melhorar e facilitar ainda mais a definição de tipos de situação em SML propondo: (i) uma maior integração da linguagem com as teorias ontológicas de modelagem conceitual pelo uso da linguagem OntoUML, visando aumentar a expressividade dos modelos de situação; e (ii) uma abordagem para validação de tipos de situação usando um método formal, visando garantir que os modelos criados correspondam à intenção do modelador. Tanto a integração quanto a validação são implementadas em uma ferramenta para especificação, verificação e validação de tipos de situação ontologicamente enriquecidos.The modeling of situation types for context-aware applications, also called situationaware applications, is, on the one hand, a key task to the proper functioning of those applications. On the other hand, it is also a hard task given the complexity and the wide range of possible situation types. Aiming at facilitating the representation of those types of situations at design-time, the Situation Modeling Language (SML) was created. This language is based partially on rich ontological theories of conceptual modeling and is accompanied by a platform for situation-detection at runtime. Despite the benefits of the availability of this suitable infrastructure, the definition of situation types, being a non-trivial task, can still pose problems that are hardly detected by modelers by manual model inspection. This thesis aims at improving and facilitating the definition of situation types in SML by proposing: (i) the integration between the language and the ontological theories of conceptual modeling by using the OntoUML language, with the purpose of increasing the expressivity of situation type models; and (ii) an approach for the validation of situation type models using a lightweight formal method, aiming at increasing the correspondence between the created models’ instances and the modeler’s intentions. Both the integration and the validation are implemented in a tool for specification, verification and validation of ontologically-enriched situation types.CAPE

Ontology Validation for Managers

Ontology driven conceptual modeling focuses on accurately representing a domain of interest, instead of making information fit an arbitrary set of constructs. It may be used for different purposes, like to achieve semantic interoperability (Nardi, Falbo and Almeida, 2013), development of knowledge representation models (Guizzardi and Zamborlini, 2012) and language evaluation (Santos, Almeida and Guizzardi,2010). Regardless its final application, a model must be accurately defined in order for it to be a successful solution. This new branch of conceptual modeling improves traditional techniques by taking into consideration ontological properties, such as rigidity, identity and dependence, which are derived from a foundational ontology. This increasing interest in more expressive languages for conceptual modeling is shown by OMGs request for language proposals for the Semantic Information Model Federation (SIMF) (OMG,2011). OntoUML (Guizzardi, 2005) is an example of a language designed for that purpose.Its metamodel (Carraretto, 2010) is designed to comply to the Unified Foundational Ontology (UFO). It focus on structural aspects of individuals and universals.Grounded on human cognition and linguistics, it aims to provide the most basic categories in which humans understand and classify things around them.In (Guizzardi, 2010) Guizzardi quotes the famous Dijkstras lecture, in which he discusses the humble programmer and makes an analogy entitled the humble ontologist. He argues that the task of ontology-driven conceptual modeling is extremely complex and thus, modelers should surround themselves with as many tools as possible to aid in the development of the ontology. These complexities arise from different sources. A couple of them come from foundational ontology itself, both its modal nature, which imposes modelers to deal with possibilities, and the many different restrictions of each ontological category. But they also come from the need of accurately defining instance level constraints, which require additional rules, outside of the languages graphical notation. To help modelers to develop high quality OntoUML models, a number of tools have been proposed to aid in different phases of conceptual modeling. From the construction of the models themselves using design patterns questions (Guizzardi et al., 2011), to automatic syntax verification (Benevides, 2010) and model validation through simulation (Benevides et al., 2010). The importance of domain specification that accurately captures the intended conceptualization has been recognized by both the traditional conceptual modeling community (Moody et al., 2003) and the ontology community (Vrandečić, 2009). In this research we want to improve (Benevides et al., 2010) initiative, but focus exclusively on the validation of ontology driven conceptual models, and not on verification. With the complexity of the modeling activity in mind, we want to help modelers to systematically produce high quality ontologies, improving precision and coverage (Gangemi et al., 2005) of the models. We intend to make the simulationbased approach available for users that are not experts in the formal method, relieving them of the need to learn yet another language, solely for the purpose of validating their models

Spatial ontologies for architectural heritage

Informatics and artificial intelligence have generated new requirements for digital archiving, information, and documentation. Semantic interoperability has become fundamental for the management and sharing of information. The constraints to data interpretation enable both database interoperability, for data and schemas sharing and reuse, and information retrieval in large datasets. Another challenging issue is the exploitation of automated reasoning possibilities. The solution is the use of domain ontologies as a reference for data modelling in information systems. The architectural heritage (AH) domain is considered in this thesis. The documentation in this field, particularly complex and multifaceted, is well-known to be critical for the preservation, knowledge, and promotion of the monuments. For these reasons, digital inventories, also exploiting standards and new semantic technologies, are developed by international organisations (Getty Institute, ONU, European Union). Geometric and geographic information is essential part of a monument. It is composed by a number of aspects (spatial, topological, and mereological relations; accuracy; multi-scale representation; time; etc.). Currently, geomatics permits the obtaining of very accurate and dense 3D models (possibly enriched with textures) and derived products, in both raster and vector format. Many standards were published for the geographic field or in the cultural heritage domain. However, the first ones are limited in the foreseen representation scales (the maximum is achieved by OGC CityGML), and the semantic values do not consider the full semantic richness of AH. The second ones (especially the core ontology CIDOC – CRM, the Conceptual Reference Model of the Documentation Commettee of the International Council of Museums) were employed to document museums’ objects. Even if it was recently extended to standing buildings and a spatial extension was included, the integration of complex 3D models has not yet been achieved. In this thesis, the aspects (especially spatial issues) to consider in the documentation of monuments are analysed. In the light of them, the OGC CityGML is extended for the management of AH complexity. An approach ‘from the landscape to the detail’ is used, for considering the monument in a wider system, which is essential for analysis and reasoning about such complex objects. An implementation test is conducted on a case study, preferring open source applications

Research in progress: report on the ICAIL 2017 doctoral consortium

This paper arose out of the 2017 international conference on AI and law doctoral consortium. There were five students who presented their Ph.D. work, and each of them has contributed a section to this paper. The paper offers a view of what topics are currently engaging students, and shows the diversity of their interests and influences

Modeling Stories for Conceptual Model Validation.

Modelagem Conceitual é uma atividade desafiadora e avaliar a qualidade de modelos conceituais produzidos é chave para garantir que possam ser usados efetivamente como base para compreensão, acordo e desenvolvimento de sistemas de informação. Modelos podem ser avaliados com relação a diferentes critérios de qualidade e neste trabalho focamos em sua acurácia em caracterizar as conceituações que visam representar. Validar a acurácia de um modelo envolve entender os mundos admissíveis que são implícitos a ele e sua adequação em representar as conceituações de domínio. Esforços anteriores para validação de modelos conceituais baseados em ontologia deram origem a um simulador de modelos que permite a modeladores ser confrontado com as consequências de suas decisões de modelagem. Esse simulador de modelos gera sequências de snapshots da instanciação de modelos, revelando a dinâmica da criação, mudança e destruição de objetos. Ainda que esses esforços contribuam para avaliação de modelos, eles podem ser difíceis de compreender e usar e este trabalho melhora a abordagem existente usando um misto de histórias formais e informais. Histórias sempre foram usadas como meio de comunicar ideias complexas e nós argumentamos que podem ser usadas efetivamente para avaliar modelos e revelar escolhas de modelagem. Esta dissertação propõe uma abordagem para avaliar modelos conceituais criando narrativas a respeito do domínio de discurso. Essas narrativas exemplificam como conceitos de um modelo conceitual são empregados em seu contexto real. Para usá-las no simulador de modelos existente, as narrativas em linguagem natural são formalizadas como histórias abstratas usando a linguagem de especificação que definimos e, então, usadas para restringir a simulação de modelos, guiando o simulador para que corresponda à narrativa, apoiando a validação do modelo conceitual. Contrastar simulações com as conceituações pretendidas é a base da avaliação de modelos nessa abordagem. A narrativa em linguagem natural permite um entendimento intuitivo do significado dos conceitos. Comparar essas narrativas a diagramas de objeto que mostram a instanciação do modelo formal permite compreender como os conceitos são formalizados

Spatial ontologies for architectural heritage

Informatics and artificial intelligence have generated new requirements for digital archiving, information, and documentation. Semantic interoperability has become fundamental for the management and sharing of information. The constraints to data interpretation enable both database interoperability, for data and schemas sharing and reuse, and information retrieval in large datasets. Another challenging issue is the exploitation of automated reasoning possibilities. The solution is the use of domain ontologies as a reference for data modelling in information systems. The architectural heritage (AH) domain is considered in this thesis. The documentation in this field, particularly complex and multifaceted, is well-known to be critical for the preservation, knowledge, and promotion of the monuments. For these reasons, digital inventories, also exploiting standards and new semantic technologies, are developed by international organisations (Getty Institute, ONU, European Union). Geometric and geographic information is essential part of a monument. It is composed by a number of aspects (spatial, topological, and mereological relations; accuracy; multi-scale representation; time; etc.). Currently, geomatics permits the obtaining of very accurate and dense 3D models (possibly enriched with textures) and derived products, in both raster and vector format. Many standards were published for the geographic field or in the cultural heritage domain. However, the first ones are limited in the foreseen representation scales (the maximum is achieved by OGC CityGML), and the semantic values do not consider the full semantic richness of AH. The second ones (especially the core ontology CIDOC – CRM, the Conceptual Reference Model of the Documentation Commettee of the International Council of Museums) were employed to document museums’ objects. Even if it was recently extended to standing buildings and a spatial extension was included, the integration of complex 3D models has not yet been achieved. In this thesis, the aspects (especially spatial issues) to consider in the documentation of monuments are analysed. In the light of them, the OGC CityGML is extended for the management of AH complexity. An approach ‘from the landscape to the detail’ is used, for considering the monument in a wider system, which is essential for analysis and reasoning about such complex objects. An implementation test is conducted on a case study, preferring open source applications