601 research outputs found

    Graph theoretic methods for the analysis of structural relationships in biological macromolecules

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    Subgraph isomorphism and maximum common subgraph isomorphism algorithms from graph theory provide an effective and an efficient way of identifying structural relationships between biological macromolecules. They thus provide a natural complement to the pattern matching algorithms that are used in bioinformatics to identify sequence relationships. Examples are provided of the use of graph theory to analyze proteins for which three-dimensional crystallographic or NMR structures are available, focusing on the use of the Bron-Kerbosch clique detection algorithm to identify common folding motifs and of the Ullmann subgraph isomorphism algorithm to identify patterns of amino acid residues. Our methods are also applicable to other types of biological macromolecule, such as carbohydrate and nucleic acid structures

    Lossless Representation of Graphs using Distributions

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    We consider complete graphs with edge weights and/or node weights taking values in some set. In the first part of this paper, we show that a large number of graphs are completely determined, up to isomorphism, by the distribution of their sub-triangles. In the second part, we propose graph representations in terms of one-dimensional distributions (e.g., distribution of the node weights, sum of adjacent weights, etc.). For the case when the weights of the graph are real-valued vectors, we show that all graphs, except for a set of measure zero, are uniquely determined, up to isomorphism, from these distributions. The motivating application for this paper is the problem of browsing through large sets of graphs.Comment: 19 page

    Integration of multi-scale protein interactions for biomedical data analysis

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    With the advancement of modern technologies, we observe an increasing accumulation of biomedical data about diseases. There is a need for computational methods to sift through and extract knowledge from the diverse data available in order to improve our mechanistic understanding of diseases and improve patient care. Biomedical data come in various forms as exemplified by the various omics data. Existing studies have shown that each form of omics data gives only partial information on cells state and motivated jointly mining multi-omics, multi-modal data to extract integrated system knowledge. The interactome is of particular importance as it enables the modelling of dependencies arising from molecular interactions. This Thesis takes a special interest in the multi-scale protein interactome and its integration with computational models to extract relevant information from biomedical data. We define multi-scale interactions at different omics scale that involve proteins: pairwise protein-protein interactions, multi-protein complexes, and biological pathways. Using hypergraph representations, we motivate considering higher-order protein interactions, highlighting the complementary biological information contained in the multi-scale interactome. Based on those results, we further investigate how those multi-scale protein interactions can be used as either prior knowledge, or auxiliary data to develop machine learning algorithms. First, we design a neural network using the multi-scale organization of proteins in a cell into biological pathways as prior knowledge and train it to predict a patient's diagnosis based on transcriptomics data. From the trained models, we develop a strategy to extract biomedical knowledge pertaining to the diseases investigated. Second, we propose a general framework based on Non-negative Matrix Factorization to integrate the multi-scale protein interactome with multi-omics data. We show that our approach outperforms the existing methods, provide biomedical insights and relevant hypotheses for specific cancer types

    Isomorphisms in co-TT graphs

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    2019 Spring.Includes bibliographical references.A threshold tolerance graph is a graph where each vertex v is assigned a weight wv and a tolerance tv, and there is an edge between two vertices vx and vy if and only if wx + wy ≥ min(tx,ty). A co-TT graph is the complement of a threshold tolerance graph. Recognition of these graphs can be done in O(n2) time; however no polynomial-time algorithm to identify isomorphisms between pairs of TT or co-TT graphs was previously known. We give an algorithm to identify these isomorphisms, which takes O(n2) time

    Site-Specific Rules Extraction in Precision Agriculture

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    El incremento sostenible en la producción alimentaria para satisfacer las necesidades de una población mundial en aumento es un verdadero reto cuando tenemos en cuenta el impacto constante de plagas y enfermedades en los cultivos. Debido a las importantes pérdidas económicas que se producen, el uso de tratamientos químicos es demasiado alto; causando contaminación del medio ambiente y resistencia a distintos tratamientos. En este contexto, la comunidad agrícola divisa la aplicación de tratamientos más específicos para cada lugar, así como la validación automática con la conformidad legal. Sin embargo, la especificación de estos tratamientos se encuentra en regulaciones expresadas en lenguaje natural. Por este motivo, traducir regulaciones a una representación procesable por máquinas está tomando cada vez más importancia en la agricultura de precisión.Actualmente, los requisitos para traducir las regulaciones en reglas formales están lejos de ser cumplidos; y con el rápido desarrollo de la ciencia agrícola, la verificación manual de la conformidad legal se torna inabordable.En esta tesis, el objetivo es construir y evaluar un sistema de extracción de reglas para destilar de manera efectiva la información relevante de las regulaciones y transformar las reglas de lenguaje natural a un formato estructurado que pueda ser procesado por máquinas. Para ello, hemos separado la extracción de reglas en dos pasos. El primero es construir una ontología del dominio; un modelo para describir los desórdenes que producen las enfermedades en los cultivos y sus tratamientos. El segundo paso es extraer información para poblar la ontología. Puesto que usamos técnicas de aprendizaje automático, implementamos la metodología MATTER para realizar el proceso de anotación de regulaciones. Una vez creado el corpus, construimos un clasificador de categorías de reglas que discierne entre obligaciones y prohibiciones; y un sistema para la extracción de restricciones en reglas, que reconoce información relevante para retener el isomorfismo con la regulación original. Para estos componentes, empleamos, entre otra técnicas de aprendizaje profundo, redes neuronales convolucionales y “Long Short- Term Memory”. Además, utilizamos como baselines algoritmos más tradicionales como “support-vector machines” y “random forests”.Como resultado, presentamos la ontología PCT-O, que ha sido alineada con otras ontologías como NCBI, PubChem, ChEBI y Wikipedia. El modelo puede ser utilizado para la identificación de desórdenes, el análisis de conflictos entre tratamientos y la comparación entre legislaciones de distintos países. Con respecto a los sistemas de extracción, evaluamos empíricamente el comportamiento con distintas métricas, pero la métrica F1 es utilizada para seleccionar los mejores sistemas. En el caso del clasificador de categorías de reglas, el mejor sistema obtiene un macro F1 de 92,77% y un F1 binario de 85,71%. Este sistema usa una red “bidirectional long short-term memory” con “word embeddings” como entrada. En relación al extractor de restricciones de reglas, el mejor sistema obtiene un micro F1 de 88,3%. Este extractor utiliza como entrada una combinación de “character embeddings” junto a “word embeddings” y una red neuronal “bidirectional long short-term memory”.<br /

    Closed-World Semantics for Query Answering in Temporal Description Logics

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    Ontology-mediated query answering is a popular paradigm for enriching answers to user queries with background knowledge. For querying the absence of information, however, there exist only few ontology-based approaches. Moreover, these proposals conflate the closed-domain and closed-world assumption, and therefore are not suited to deal with the anonymous objects that are common in ontological reasoning. Many real-world applications, like processing electronic health records (EHRs), also contain a temporal dimension, and require efficient reasoning algorithms. Moreover, since medical data is not recorded on a regular basis, reasoners must deal with sparse data with potentially large temporal gaps. Our contribution consists of three main parts: Firstly, we introduce a new closed-world semantics for answering conjunctive queries with negation over ontologies formulated in the description logic ELH⊥, which is based on the minimal universal model. We propose a rewriting strategy for dealing with negated query atoms, which shows that query answering is possible in polynomial time in data complexity. Secondly, we introduce a new temporal variant of ELH⊥ that features a convexity operator. We extend this minimal-world semantics for answering metric temporal conjunctive queries with negation over the logic and obtain similar rewritability and complexity results. Thirdly, apart from the theoretical results, we evaluate minimal-world semantics in practice by selecting patients, based their EHRs, that match given criteria

    Graph embedding in SYNCHEM2, an expert system for organic synthesis discovery

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    AbstractGraph embedding (subgraph isomorphism) is an NP-complete problem of great theoretical and practical importance in the sciences, especially chemistry and computer science. This paper presents positive test results for techniques to speed embedding by modeling graphs with subroutines, precalculating edge tables, turning recursion into iteration, and using search-ordering heuristics.The expert system synchem2 searches for synthesis routes of organic molecules without the online guidance of a user, and this paper examines how embedding information helps to implement the central operations of synchem2: selection, application, and evaluation of chemical reactions. The paper also outlines the architecture of synchem2, analyzes the computational time complexity of embedding and related problems in graph isomorphism and canonical chemical naming, and suggests topics and techniques for further research

    Graph theoretic models

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23224/1/0000157.pd
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