Multiple sequence alignment correction using constraints

Trabalho apresentado no âmbito do European Master in Computational Logics, como requisito parcial para obtenção do grau de Mestre em Computational LogicsOne of the most important fields in bioinformatics has been the study of protein sequence alignments. The study of homologous proteins, related by evolution, shows the conservation of many amino acids because of their functional and structural importance. One particular relationship between the amino acid sites in the same sequence or between different sequences, is protein-coevolution, interest in which has increased as a consequence of mathematical and computational methods used to understand the spatial, functional and evolutionary dependencies between amino acid sites. The principle of coevolution means that some amino acids are related through evolution because mutations in one site can create evolutionary pressures to select compensatory mutations in other sites that are functionally or structurally related. With the actual methods to detect coevolution, specifically mutual information techniques from the information theory field, we show in this work that much of the information between coevolved sites is lost because of mistakes in the multiple sequence alignment of variable regions. Moreover, we show that using these statistical methods to detect coevolved sites in multiple sequence alignments results in a high rate of false positives. Due to the amount of errors in the detection of coevolved site from multiple sequence alignments, we propose in this work a method to improve the detection efficacy of coevolved sites and we implement an algorithm to fix such sites correcting the misalignment produced in those specific locations. The detection part of our work is based on the mutual information between sites that are guessed as having coevolved, due to their high statistical correlation score. With this information we search for possible misalignments on those regions due to the incorrect matching of amino acids during the alignment. The re-alignment part is based on constraint programming techniques, to avoid the combinatorial complexity when one amino acid can be aligned with many others and to avoid inconsistencies in the alignments. In this work, we present a framework to impose constraints over the sequences, and we show how it is possible to compute alignments based on different criteria just by setting constraint between the amino acids. This framework can be applied not only for improving the alignment and detection of coevolved regions, but also to any desired constraints that may be used to express functional or structural relations among the amino acids in multiple sequences. We show also that after we fix these misalignments, using constraints based techniques, the correlation between coevolved sites increases and, in general, the new alignment is closer to the correct alignment than the MSA alignment. Finally, we show possible future research lines with the objective of overcoming some drawbacks detected during this work

Framework para detección de intrusos usando DeLP

Uno de los principales problemas que se presentan en las redes de mediana y gran escala es la dificultad para monitorear y detectar vulnerabilidades que puedan ser explotadas. Tanto los recursos que se comparten en una red, como los principales hosts que intervienen en la misma quedan expuestos a posibles ataques que pueden causar pérdidas considerables en los datos. En esta línea de investigación se pretende desarrollar un framework de detección de intrusos, donde todos los hosts que participan de una red puedan argumentar si una vulnerabilidad en algún host puede ser explotada. Es necesario entonces un mecanismo para poder informar la configuración de cada host y de toda entidad que participe en la red, para luego razonar en forma argumentativa sobre un potencial ataque. Para esta representación de conocimiento e inferencia se utiliza programación en lógica rebatible, Defeasible Logic Programming (DeLP). Además se tratan de analizar brevemente los problemas derivados de la estructura del framework y de la lógica. Dichos problemas impactan negativamente sobre la seguridad, performance y escalabilidad del sistema propuesto.Eje: Procesamiento Concurrente, Paralelo y DistribuidoRed de Universidades con Carreras en Informática (RedUNCI

Framework para detección de intrusos usando DeLP

Uno de los principales problemas que se presentan en las redes de mediana y gran escala es la dificultad para monitorear y detectar vulnerabilidades que puedan ser explotadas. Tanto los recursos que se comparten en una red, como los principales hosts que intervienen en la misma quedan expuestos a posibles ataques que pueden causar pérdidas considerables en los datos. En esta línea de investigación se pretende desarrollar un framework de detección de intrusos, donde todos los hosts que participan de una red puedan argumentar si una vulnerabilidad en algún host puede ser explotada. Es necesario entonces un mecanismo para poder informar la configuración de cada host y de toda entidad que participe en la red, para luego razonar en forma argumentativa sobre un potencial ataque. Para esta representación de conocimiento e inferencia se utiliza programación en lógica rebatible, Defeasible Logic Programming (DeLP). Además se tratan de analizar brevemente los problemas derivados de la estructura del framework y de la lógica. Dichos problemas impactan negativamente sobre la seguridad, performance y escalabilidad del sistema propuesto.Eje: Procesamiento Concurrente, Paralelo y DistribuidoRed de Universidades con Carreras en Informática (RedUNCI

Computación distribuida de alto rendimiento y disponibilidad: desarrollo y perspectiva

Los avances de la tecnología informática y la baja de costos del equipamiento hicieron realidad, en las últimas décadas, el desarrollo de los sistemas distribuidos. Basados en sistemas seguros de comunicación y computadoras personales o estaciones de trabajo cada vez más veloces, han madurado en su concepci ón y desarrollo. Por un lado con este soporte, arquitectura física y arquitectura de programación o algorítmica, se desarrollan aplicaciones geográ ca y administrativamente distribuidas. Esto presenta el desafío de lograr el mejor aprovechamiento y rendimiento de todo el sistema. En este sentido se orienta el estudio de la computación colaborativa , computación paralela y distribuida de alta disponibilidad . En este escrito se presenta un resumen de avance del proyecto iniciado hace tres años y cuáles son las perspectivas dentro del mismo.Eje: Procesamiento Concurrente, Paralelo y DistribuidoRed de Universidades con Carreras en Informática (RedUNCI

Computación distribuida de alto rendimiento y disponibilidad: desarrollo y perspectiva

Los avances de la tecnología informática y la baja de costos del equipamiento hicieron realidad, en las últimas décadas, el desarrollo de los sistemas distribuidos. Basados en sistemas seguros de comunicación y computadoras personales o estaciones de trabajo cada vez más veloces, han madurado en su concepci ón y desarrollo. Por un lado con este soporte, arquitectura física y arquitectura de programación o algorítmica, se desarrollan aplicaciones geográ ca y administrativamente distribuidas. Esto presenta el desafío de lograr el mejor aprovechamiento y rendimiento de todo el sistema. En este sentido se orienta el estudio de la computación colaborativa , computación paralela y distribuida de alta disponibilidad . En este escrito se presenta un resumen de avance del proyecto iniciado hace tres años y cuáles son las perspectivas dentro del mismo.Eje: Procesamiento Concurrente, Paralelo y DistribuidoRed de Universidades con Carreras en Informática (RedUNCI

Online dispute resolution: an artificial intelligence perspective

Litigation in court is still the main dispute resolution mode. However, given the amount and characteristics of the new disputes, mostly arising out of electronic contracting, courts are becoming slower and outdated. Online Dispute Resolution (ODR) recently emerged as a set of tools and techniques, supported by technology, aimed at facilitating conflict resolution. In this paper we present a critical evaluation on the use of Artificial Intelligence (AI) based techniques in ODR. In order to fulfill this goal, we analyze a set of commercial providers (in this case twenty four) and some research projects (in this circumstance six). Supported by the results so far achieved, a new approach to deal with the problem of ODR is proposed, in which we take on some of the problems identified in the current state of the art in linking ODR and AI.The work described in this paper is included in TIARAC - Telematics and Artificial Intelligence in Alternative Conflict Resolution Project (PTDC/JUR/71354/2006), which is a research project supported by FCT (Science & Technology Foundation), Portugal. The work of Davide Carneiro is also supported by a doctoral grant by FCT (SFRH/BD/64890/2009).Acknowledgments. The work described in this paper is included in TIARAC - Telematics and Artificial Intelligence in Alternative Conflict Resolution Project (PTDC/JUR/71354/2006), which is a research project supported by FCT (Science & Technology Foundation), Portugal. The work of Davide Carneiro is also supported by a doctoral grant by FCT (SFRH/BD/64890/2009)

IL21R expressing CD14+CD16+ monocytes expand in multiple myeloma patients leading to increased osteoclasts

Bone marrow monocytes are primarily committed to osteoclast formation. It is, however, unknown whether potential primary alterations are specifically present in bone marrow monocytes of multiple myeloma patients, smoldering myeloma or monoclonal gammopathy of uncertain significance. Herein, we analyzed the immunophenotypic and transcriptional profiles of bone marrow CD14+ monocytes in a cohort of patients with different types of monoclonal gammopathies to identify alterations involved in myeloma-enhanced osteoclastogenesis. A higher number of bone marrow CD14+CD16+ cells was found in patients with active myeloma as compared to those with smoldering myeloma and monoclonal gammopathy of uncertain significance. Interestingly, sorted bone marrow CD14+CD16+ cells from myeloma patients were more pro-osteoclastogenic than CD14+CD16- cells in cultures ex vivo. Moreover, transcriptional analysis demonstrated that bone marrow multiple myeloma (but neither monoclonal gammopathy of uncertain significance nor smoldering myeloma) CD14+ cells significantly upregulated genes involved in osteoclast formation, including IL21R. IL21R mRNA over-expression by bone marrow CD14+ cells was independent from the presence of IL-21. Consistently, IL-21 production by T cells as well as IL-21 bone marrow levels were not significantly different among monoclonal gammopathies. Thereafter, we showed that IL21R over-expression in CD14+ cells increased osteoclast formation. Consistently, IL-21R signaling inhibition by Janex 1 suppressed osteoclast differentiation from bone marrow CD14+ cells of myeloma patients. Our results indicated that multiple myeloma patients showed distinct bone marrow monocyte features compared to those with indolent monoclonal gammopathies, supporting the role of IL21R over-expression by bone marrow CD14+ cells in enhanced osteoclast formation