Finding similar or diverse solutions in answer set programming: theory and applications

For many computational problems, the main concern is to find a best solution (e.g., a most preferred product configuration, a shortest plan, a most parsimonious phylogeny) with respect to some well-described criteria. On the other hand, in many real-world applications, computing a subset of good solutions that are similar/diverse may be desirable for better decision-making. For one reason, the given computational problem may have too many good solutions, and the user may want to examine only a few of them to pick one; in such cases, finding a few similar/diverse good solutions may be useful. Also, in many real-world applications the users usually take into account further criteria that are not included in the formulation of the optimization problem; in such cases, finding a few good solutions that are close to or distant from a particular set of solutions may be useful. With this motivation, we have studied various computational problems related to finding similar/diverse (resp. close/distant) solutions with respect to a given distance function, in the context of Answer Set Programming (ASP). We have introduced novel offline/online computational methods in ASP to solve such computational problems. We have modified an ASP solver according to one of our online methods, providing a useful tool (CLASP-NK) for various ASP applications. We have showed the applicability and effectiveness of our methods/tools in three domains: phylogeny reconstruction, AI planning, and biomedical query answering. Motivated by the promising results, we have developed computational tools to be used by the experts in these areas

Semantic resources in pharmacovigilance: a corpus and an ontology for drug-drug interactions

Mención Internacional en el título de doctorNowadays, with the increasing use of several drugs for the treatment of one or more different diseases (polytherapy) in large populations, the risk for drugs combinations that have not been studied in pre-authorization clinical trials has increased. This provides a favourable setting for the occurrence of drug-drug interactions (DDIs), a common adverse drug reaction (ADR) representing an important risk to patients safety, and an increase in healthcare costs. Their early detection is, therefore, a main concern in the clinical setting. Although there are different databases supporting healthcare professionals in the detection of DDIs, the quality of these databases is very uneven, and the consistency of their content is limited. Furthermore, these databases do not scale well to the large and growing number of pharmacovigilance literature in recent years. In addition, large amounts of current and valuable information are hidden in published articles, scientific journals, books, and technical reports. Thus, the large number of DDI information sources has overwhelmed most healthcare professionals because it is not possible to remain up to date on everything published about DDIs. Computational methods can play a key role in the identification, explanation, and prediction of DDIs on a large scale, since they can be used to collect, analyze and manipulate large amounts of biological and pharmacological data. Natural language processing (NLP) techniques can be used to retrieve and extract DDI information from pharmacological texts, supporting researchers and healthcare professionals on the challenging task of searching DDI information among different and heterogeneous sources. However, these methods rely on the availability of specific resources providing the domain knowledge, such as databases, terminological vocabularies, corpora, ontologies, and so forth, which are necessary to address the Information Extraction (IE) tasks. In this thesis, we have developed two semantic resources for the DDI domain that make an important contribution to the research and development of IE systems for DDIs. We have reviewed and analyzed the existing corpora and ontologies relevant to this domain, based on their strengths and weaknesses, we have developed the DDI corpus and the ontology for drug-drug interactions (named DINTO). The DDI corpus has proven to fulfil the characteristics of a high-quality gold-standard, and has demonstrated its usefulness as a benchmark for the training and testing of different IE systems in the SemEval-2013 DDIExtraction shared task. Meanwhile, DINTO has been used and evaluated in two different applications. Firstly, it has been proven that the knowledge represented in the ontology can be used to infer DDIs and their different mechanisms. Secondly, we have provided a proof-of-concept of the contribution of DINTO to NLP, by providing the domain knowledge to be exploited by an IE pilot prototype. From these results, we believe that these two semantic resources will encourage further research into the application of computational methods to the early detection of DDIs. This work has been partially supported by the Regional Government of Madrid under the Research Network MA2VICMR [S2009/TIC-1542], by the Spanish Ministry of Education under the project MULTIMEDICA [TIN2010-20644-C03-01] and by the European Commission Seventh Framework Programme under TrendMiner project [FP7-ICT287863].Hoy en día ha habido un notable aumento del número de pacientes polimedicados que reciben simultáneamente varios fármacos para el tratamiento de una o varias enfermedades. Esta situación proporciona el escenario ideal para la prescripción de combinaciones de fármacos que no han sido estudiadas previamente en ensayos clínicos, y puede dar lugar a un aumento de interacciones farmacológicas (DDIs por sus siglas en inglés). Las interacciones entre fármacos son un tipo de reacción adversa que supone no sólo un riesgo para los pacientes, sino también una importante causa de aumento del gasto sanitario. Por lo tanto, su detección temprana es crucial en la práctica clínica. En la actualidad existen diversos recursos y bases de datos que pueden ayudar a los profesionales sanitarios en la detección de posibles interacciones farmacológicas. Sin embargo, la calidad de su información varía considerablemente de unos a otros, y la consistencia de sus contenidos es limitada. Además, la actualización de estos recursos es difícil debido al aumento que ha experimentado la literatura farmacológica en los últimos años. De hecho, mucha información sobre DDIs se encuentra dispersa en artículos, revistas científicas, libros o informes técnicos, lo que ha hecho que la mayoría de los profesionales sanitarios se hayan visto abrumados al intentar mantenerse actualizados en el dominio de las interacciones farmacológicas. La ingeniería informática puede representar un papel fundamental en este campo permitiendo la identificación, explicación y predicción de DDIs, ya que puede ayudar a recopilar, analizar y manipular grandes cantidades de datos biológicos y farmacológicos. En concreto, las técnicas del procesamiento del lenguaje natural (PLN) pueden ayudar a recuperar y extraer información sobre DDIs de textos farmacológicos, ayudando a los investigadores y profesionales sanitarios en la complicada tarea de buscar esta información en diversas fuentes. Sin embargo, el desarrollo de estos métodos depende de la disponibilidad de recursos específicos que proporcionen el conocimiento del dominio, como bases de datos, vocabularios terminológicos, corpora u ontologías, entre otros, que son necesarios para desarrollar las tareas de extracción de información (EI). En el marco de esta tesis hemos desarrollado dos recursos semánticos en el dominio de las interacciones farmacológicas que suponen una importante contribución a la investigación y al desarrollo de sistemas de EI sobre DDIs. En primer lugar hemos revisado y analizado los corpora y ontologías existentes relevantes para el dominio y, en base a sus potenciales y limitaciones, hemos desarrollado el corpus DDI y la ontología para interacciones farmacológicas DINTO. El corpus DDI ha demostrado cumplir con las características de un estándar de oro de gran calidad, así como su utilidad para el entrenamiento y evaluación de distintos sistemas en la tarea de extracción de información SemEval-2013 DDIExtraction Task. Por su parte, DINTO ha sido utilizada y evaluada en dos aplicaciones diferentes. En primer lugar, hemos demostrado que esta ontología puede ser utilizada para inferir interacciones entre fármacos y los mecanismos por los que ocurren. En segundo lugar, hemos obtenido una primera prueba de concepto de la contribución de DINTO al área del PLN al proporcionar el conocimiento del dominio necesario para ser explotado por un prototipo de un sistema de EI. En vista de estos resultados, creemos que estos dos recursos semánticos pueden estimular la investigación en el desarrollo de métodos computaciones para la detección temprana de DDIs. Este trabajo ha sido financiado parcialmente por el Gobierno Regional de Madrid a través de la red de investigación MA2VICMR [S2009/TIC-1542], por el Ministerio de Educación Español, a través del proyecto MULTIMEDICA [TIN2010-20644-C03-01], y por el Séptimo Programa Macro de la Comisión Europea a través del proyecto TrendMiner [FP7-ICT287863].This work has been partially supported by the Regional Government of Madrid under the Research Network MA2VICMR [S2009/TIC-1542], by the Spanish Ministry of Education under the project MULTIMEDICA [TIN2010-20644-C03-01] and by the European Commission Seventh Framework Programme under TrendMiner project [FP7-ICT287863].Programa Oficial de Doctorado en Ciencia y Tecnología InformáticaPresidente: Asunción Gómez Pérez.- Secretario: María Belén Ruiz Mezcua.- Vocal: Mariana Neve

Generating explanations for complex biomedical queries

Recent advances in health and life sciences have led to generation of a large amount of biomedical data. To facilitate access to its desired parts, such a big mass of data has been represented in structured forms, like databases and ontologies. On the other hand, representing these databases and ontologies in different formats, constructing them independently from each other, and storing them at different locations have brought about many challenges for answering queries about the knowledge represented in these ontologies and databases. One of the challenges for the users is to be able to represent such a biomedical query in a natural language, and get its answers in an understandable form. Another challenge is to extract relevant knowledge from different knowledge resources, and integrate them appropriately using also definitions, such as, chains of gene-gene interactions, cliques of genes based on gene-gene relations, or similarity/diversity of genes/drugs. Furthermore, once an answer is found for a complex query, the experts may need further explanations about the answer. The first two challenges have been addressed earlier using Answer Set Programming (ASP), with the development of a software system (called BIOQUERY-ASP). This thesis addresses the third challenge: explanation generation in ASP. In this thesis, we extend the earlier work on the first two challenges, to new forms of biomedical queries (e.g., about drug similarity) and to new biomedical knowledge resources. We introduce novel mathematical models and algorithms to generate (shortest or k different) explanations for queries in ASP, and provide a comprehensive theoretical analysis of these methods. We implement these algorithms and integrate them in BIOQUERY-ASP, and provide an experimental evaluation of our methods with some complex biomedical queries over the biomedical knowledge resources PHARMGKB, DRUGBANK, BIOGRID, CTD, SIDER, DISEASEONTOLOGY and ORPHADATA

Reasoning about Triggered Actions in AnsProlog and its Application to Molecular Interactions in Cells

Reasoning about molecular interactions and signaling pathways is important from various perspectives such as predicting side effects of drugs, explaining unusual cellular behavior and drug and therapy design. Because of the vast size of these interactions a typical biologist can only focus on a very small part of the network. Thus there is a great need to develop knowledge representation and reasoning formalisms and their implementations for modelling and reasoning about molecular interactions in cells of organisms. An important component of these interactions is the action of one molecule interacting with or binding to another, or one molecule separating into multiple other molecules. Thus, action theories and action languages are good candidates to model these interactions. One major lacking of most existing action languages is the notion of triggered actions, which is a common phenomena in the cellular domain. In this paper, we introduce a language for representing and reasoning about triggered actions, and show how to model reasoning about side effects, explaining observations, and designing drugs in our language through implementations using AnsProlog

Proceedings of the 11th Workshop on Nonmonotonic Reasoning

These are the proceedings of the 11th Nonmonotonic Reasoning Workshop. The aim of this series is to bring together active researchers in the broad area of nonmonotonic reasoning, including belief revision, reasoning about actions, planning, logic programming, argumentation, causality, probabilistic and possibilistic approaches to KR, and other related topics. As part of the program of the 11th workshop, we have assessed the status of the field and discussed issues such as: Significant recent achievements in the theory and automation of NMR; Critical short and long term goals for NMR; Emerging new research directions in NMR; Practical applications of NMR; Significance of NMR to knowledge representation and AI in general