Flujos de trabajo sistemáticos para el análisis computacional de datos proteómicos

Trabajo de fin de Grado. Grado en Estadística. Curso académico 2020-2021.[ES]La proteómica es el estudio de los proteomas, donde se separan, identifican y caracterizan proteínas a gran escala. Se utilizaron técnicas de espectrometría de masas para obtener cuantificación de proteínas y max-quant para obtener sus intensidades en muestras de los estadios del linfocito b y de leucemia linfocítica crónica. A través de técnicas estadísticas, se pueden encontrar relaciones entre todos los tipos celulares y, a través de técnicas bioinformáticas, se pueden encontrar rutas de señalización de proteínas involucradas y su ubicación celular.[EN]Proteomics is the study of proteomes, where they separate, identify and characterize proteins on a large scale. Mass spectrum-metrics techniques were used to obtain protein and max-quant quantification to obtain their intensities in samples from the stages of lymphocyte b and chronic lymphocytic leukemia. Through statistical techniques, relations between all cell types can be contracted and, through bioinformatic techniques, pathways of protein signaling involved and their cell location can be foun

Deciphering biomarkers for leptomeningeal metastasis in malignant hemopathies (Lymphoma/Leukemia) patients by comprehensive multipronged proteomics characterization of cerebrospinal fluid

In the present work, leptomeningeal disease, a very destructive form of systemic cancer, was characterized from several proteomics points of view. This pathology involves the invasion of the leptomeninges by malignant tumor cells. The tumor spreads to the central nervous system through the cerebrospinal fluid (CSF) and has a very grim prognosis; the average life expectancy of patients who suffer it does not exceed 3 months. The early diagnosis of leptomeningeal disease is a challenge because, in most of the cases, it is an asymptomatic pathology. When the symptoms are clear, the disease is already in the very advanced stages and life expectancy is low. Consequently, there is a pressing need to determine useful CSF proteins to help in the diagnosis and/or prognosis of this disease. For this purpose, a systematic and exhaustive proteomics characterization of CSF by multipronged proteomics approaches was performed to determine different protein profiles as potential biomarkers. Proteins such as PTPRC, SERPINC1, sCD44, sCD14, ANPEP, SPP1, FCGR1A, C9, sCD19, and sCD34, among others, and their functional analysis, reveals that most of them are linked to the pathology and are not detected on normal CSF. Finally, a panel of biomarkers was verified by a prediction model for leptomeningeal disease, showing new insights into the research for potential biomarkers that are easy to translate into the clinic for the diagnosis of this devastating disease.We gratefully acknowledge financial support from the Spanish Health Institute, Carlos III (ISCIII), for the grants: FIS PI14/01538, FIS PI17/01930 and CB16/12/00400. We also acknowledge Fondos FEDER (EU) and Junta Castilla-León (COVID-19 grant COV20EDU/00187). The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023 of the PE I + D + I2017-2020, funded by ISCIII and FEDER—Norma Galicia is supported by the CONACYT Program. P. Juanes-Velasco is supported by JCYL PhD Program “Nos Impulsa-JCYL” and scholarship JCYLEDU/601/2020

Caribbean Corals in Crisis: Record Thermal Stress, Bleaching, and Mortality in 2005

BACKGROUND The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. METHODOLOGY/PRINCIPAL FINDINGS Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. CONCLUSIONS/SIGNIFICANCE Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.This work was partially supported by salaries from the NOAA Coral Reef Conservation Program to the NOAA Coral Reef Conservation Program authors. NOAA provided funding to Caribbean ReefCheck investigators to undertake surveys of bleaching and mortality. Otherwise, no funding from outside authors' institutions was necessary for the undertaking of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature

Primary Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population

Coulomb dissociation of 16O into 4He and 12C

We measured the Coulomb dissociation of 16O into 4He and 12C at the R3B setup in a first campaign within FAIR Phase 0 at GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt. The goal was to improve the accuracy of the experimental data for the 12C(a,?)16O fusion reaction and to reach lower center-ofmass energies than measured so far. The experiment required beam intensities of 109 16O ions per second at an energy of 500 MeV/nucleon. The rare case of Coulomb breakup into 12C and 4He posed another challenge: The magnetic rigidities of the particles are so close because of the same mass-To-charge-number ratio A/Z = 2 for 16O, 12C and 4He. Hence, radical changes of the R3B setup were necessary. All detectors had slits to allow the passage of the unreacted 16O ions, while 4He and 12C would hit the detectors' active areas depending on the scattering angle and their relative energies. We developed and built detectors based on organic scintillators to track and identify the reaction products with sufficient precision

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Wake on LAN over Internet as web service system on chip

En este artículo presentamos un System on Chip (SoC) diseñado para ejecutar un Web Service (WS) concreto en un Application-Specific Integrated Circuit (ASIC). El sistema se ha diseñado sin procesador y sin software y se ha concebido como un patrón de diseño hardware para un fácil desarrollo de servicios de red que se ofrecen como WS bajo un enfoque de Arquitecturas Orientadas a Servicio. Por tanto, el chip no sólo es capaz de actuar como un Proveedor de Servicios SOAP sino que también es capaz, por si sólo, de registrar el servicio en un Servidor de Registro externo mediante el protocolo estándar de publicación UDDI. Esta propuesta se ha denominado WSoC. El objetivo principal de este WSoC es desarrollar dispositivos de red SOA más viables económicamente hablando y con mantenimiento cero. Para validar la propuesta, se ha implementado un prototipo mediante el uso de la tecnología FPGA. En concreto, se ha seleccionado el servicio de red WoL over Internet, que permite que cualquier cliente WS encienda cualquier dispositivo de red compatible con la tecnología WoL. También se ha desarrollado un escenario completo SOA para testear las funciones del prototipo, validando la propuesta

Preservación y difusión del Fondo Histórico de la Universidad de la Sabana

En el contexto de las instituciones de educación superior la excelente acogida y utilización de los repositorios digitales han generado multitud de nuevos/as requerimientos/necesidades de incorporación de contenidos digitales. Esta circunstancia explica, entre otras, que los repositorios de viejo cuño, originariamente concebidos como sistemas de captura, preservación y difusión del patrimonio científico-académico de las instituciones, se hayan visto forzados a gestionar material digital que a menudo exceden sus capacidades funcionales. Un caso especial que tratamos en el presente estudio es la incorporación de los Fondos Antiguos e Históricos. Este tipo de material digital presenta particularidades digitales muy específicas derivadas principalmente de los propios fondos y el proceso de obtención de la copia digital. A menudo este hecho genera desencuentros entre las políticas de conservación y divulgación institucionales. Como es conocido, la denominada copia digital de preservación, producto de una primera fase de ese proceso de digitalización, se traduce en archivos de mucha definición, calidad y por lo tanto de enorme tamaño para ser gestionados correctamente desde el punto de vista de su accesibilidad. En el polo opuesto, sin embargo, las copias de consulta han sacrificado la calidad de los archivos en favor de su acceso. Recientemente, además, otra derivada se ha añadido a esta problemática, a saber, la “movilización” de contenidos y los nuevos requerimientos a sus futuras representaciones (e.g., la adaptación a su visualización por dispositivos móviles, etc.). El dilema de este modo está servido, ¿preservación y difusión son incompatibles? Creemos que no. En adelante presentaremos a lo largo de la comunicación los trabajos realizados en el repositorio intellectum de la Universidad de la Sabana. Todos ellos muestran las soluciones implementadas ad hoc para solucionar los problemas anteriormente mencionados, a saber: la incorporación de un Fondo Histórico de especial importancia y tamaño con arreglo a los requerimientos de máxima calidad y difusión (acceso) de las copias de preservación, copias de consulta y representaciones adicionales para diferentes usuarios y dispositivos de acceso. El Instituto de Humanidades de la Universidad de la Sabana recibió el año 2005 en donación dos colecciones con aproximadamente 40.000 folios de los siglos XVIII, XIX y XX, correspondientes a los fondos documentales Manuel María Mosquera y David Mejía Velilla. El proyecto, con importantes actuaciones de infraestructura en la Biblioteca Octavio Arizmendi Posada de la Universidad, integró estos fondos en el Archivo Histórico Cipriano Rodríguez Santa María. Como fase ya ejecutadas podemos mencionar actuaciones de identificación, clasificación, descripción, elaboración de herramientas de consulta y control de calidad. En la fase actual se está procediendo progresivamente a la digitalización, catalogación, microfilmación y subida al repositorio institucional intellectum. Esta subida se efectúa mediante procedimientos de metadatación y creación de paquetes de ingesta específicamente diseñados para optimizar los flujos de trabajo de los agentes del proceso. En intellectum, repositorio construido con el software DSpace, se ha realizado un enfoque en el que coexisten las soluciones específicas de preservación de los fondos documentales antedichos con las igualmente específicas de difusión y visualización, de forma amplia, para una variedad de usuarios y dispositivos de acceso. El sistema de ingesta de intellectum está orientado al depósito de las digitalizaciones en formato jpeg de alta calidad resultantes del proceso de digitalización por los responsables de los fondos históricos. Estas digitalizaciones son los objetos principales de los sistemas de preservación que incorpora DSpace en la actualidad (y los que adicionalmente se incorporen en el futuro). Por su gran tamaño, derivado de su alta definición, estos ficheros no se ponen a disposición de los usuarios generales, almacenándose en un bundle específico exclusivamente accedidos por las funcionalidades de preservación del DSpace y por los usuarios administradores de intellectum. Posteriormente un conjunto de tareas automáticas de curación ensamblan a partir de esas copias de preservación diversas versiones o representaciones de cada objeto. En concreto, en la versión actual de intellectum, se ensamblan los ficheros de preservación en un único fichero en formato pdf multipágina apto para su descarga por todo tipo de usuarios (almacenado en un bundle accesible) o como representación en formato flash apta para un visor pseudo-streming (específico de intellectum). La ventaja de este enfoque reside en generar en tiempo nuevas copias o representaciones de cada objeto digital sin necesidad de realizar una re-ingesta de los ficheros. De este modo, la adaptabilidad y flexibilidad del sistema son máximas al facilitar el acceso y representación de los objetos digitales con un mínimo esfuerzo, sea cual sea la evolución tecnológica o la opción de acceso de los usuarios. Una última virtud de este modelo es la posibilidad de desechar representaciones que devengan obsoletas, ya que las copias maestras, las realmente valiosas a efectos de preservación, seguirán existiendo en DSpace. Las posibilidades son múltiples y están imbricadas precisamente en el enfoque multinivel de almacenamiento descrito

Network intrusion detection system embedded on a smart sensor

This paper proposes a Network Intrusion Detection System (NIDS) embedded in an Smart Sensor inspired device, under a Service Oriented Architecture (SOA) approach, able to operate independently as an anomaly-based NIDS or integrated, transparently, in a Distributed Intrusion Detection System (DIDS). The proposal is innovative, because it combines the advantages of Smart Sensor approach and the subsequent offering of the NIDS functionality as a service with the SOA use in order to achieve their integration with other DIDS components. The main goal of the work is to reduce the huge volume of management tasks inherent to this type of network services, as well as facilitating the design of DIDS whose managing complexity could be restricted within well defined margins. The work also addresses the construction of a physical sensor prototype. This prototype was used to carry out the tests that has demonstrated the proposals validity, providing detection and performance ratios similar to those of existing IDS, but with the advantage of a zero-maintenance approach

Reinfection rate and disease severity of the BA.5 Omicron SARS-CoV-2 lineage compared to previously circulating variants of concern in the Canary Islands (Spain)

ABSTRACTThe emergence of the Omicron SARS-CoV-2 variant of concern has changed the COVID-19 scenario as this variant is characterized by high transmissibility and immune evasion ability. To evaluate the impact of this variant on the Canary Islands (Spain) population, we determined the reinfection rates and disease severity associated with the Omicron sublineages and the previously circulating variants of concern. We performed a retrospective observational study on 21,745 SARS-CoV-2 viral genomes collected from December 2020 to July 2022 in the Canary Islands (Spain). We compared the reinfection rates between lineages using pairwise proportion and Fisher’s exact tests. To assess disease severity, we studied the association of Alpha, Delta, BA.1, BA.2, BA.5, and other risk factors on 28-day hospital mortality using logistic regression and Cox proportional hazard models. We observed 127 bona fide reinfection cases throughout the study period. We found that BA.5 had the highest reinfection rate compared to other lineages (vs. Delta p = 2.89 × 10−25; vs. BA.1 p = 5.17 × 10−11; vs. BA.2 p = 0.002). Among the 1,094 hospitalized patients, multivariate logistic regression showed that Alpha (Odds Ratio [OR] =  0.45, 95% Confidence Interval [CI] =  0.23-0.87, p = 0.02), BA.2 (OR =   0.38, 95% CI = 0.22-0.63, p = 1.91 × 10−4), and BA.5 (OR = 0.30, 95% CI = 0.16-0.55, p = 1.05 × 10−4) had lower 28-day hospital mortality compared to Delta. These results were confirmed by using Cox proportional hazard models. Omicron lineages, and in particular BA.5, were associated with higher reinfection rates and lower disease severity (28-day hospital mortality) than previously circulating variants of concern