Herramientas eficientes para el análisis masivo de datos ómicos

En los últimos años se han desarrollado técnicas en el campo de la biología que han revolucionado las áreas de la genómica y la proteómica. Estas técnicas, entre las que se encuentran la secuenciación masiva y la proteómica de Shotgun, nos están permitiendo un conocimiento mucho más profundo del funcionamiento de las células, pudiendo ver qué ARN mensajero y proteínas están presentes en un momento puntual de las mismas, además de conocer mejor algunos mecanismos de regulación. Con el desarrollo de estas tecnologías, se están generando más datos de los que es posible procesar en una cantidad razonable de tiempo. Es necesario el desarrollo de nuevas herramientas que manejen este tipo de datos de una forma eficiente, haciendo uso de técnicas de computación de altas prestaciones que incluyan el uso de granjas de computación, computación paralela y gestión de plataformas virtualizadas. En la presente tesis se pretende realizar un abordaje integral del análisis masivo de datos provenientes de estastécnicas con herramientas eficientes, empezando por el procesamiento de los datos en crudo y obteniendo información de más alto nivel sobre expresión de genes y proteínas, enriqueciéndola con información relacionada de bases de datos y ontologías de libre acceso, para finalmente generar informes que reflejen el funcionamiento celular asociado a toda esta información. También incluye el desarrollo de herramientas generadoras de hipótesis en el ámbito de la regulación génica, que sirvan a biólogos experimentalistas para el desarrollo de nuevos experimentos de validación. Este abordaje se ha concretado en el desarrollo de diferentes metodologías y herramientas. Primeramente se han desarrollado varios flujos de trabajo para análisis de RNA-Seq, Microarrays y proteómica de Shotgun de diferentes proyectos y bases de datos públicas tales como ENCODE, Human Proteome Project, Illumina Human Body Map o the Cancer Cell Line Encyclopedia, enfocados para realizar estudios proteogenómicos, permitiendo detectar con exactitud los genes expresados sin necesidad de un control, o mezclar datos transcriptómicos y proteómicos para poder realizar una mejor detección de proteínas..

Paralelización con CUDA de algoritmos de verificación facial

Los delitos y fraudes derivados de la suplantación de identidad generan pérdidas millonarias para empresas y naciones. Hoy en día existen diversos métodos biométricos para la verificación de identidad. Entre ellos se encuentra la verificación facial, de gran interés práctico por su carácter no intrusivo. Los algoritmos que se aplican para la verificación facial tienen un alto coste computacional, dificultando su uso en aplicaciones de tiempo real. Sin embargo estos algoritmos presentan un alto grado de paralelismo a nivel de datos que podría explotarse xon plataformas multicore. En la actualidad uno de los principales exponentes de las plataformas multicore son las unidades de procesamiento gráfico (GPU). En este proyecto se ha abordado la implementación de diversos algoritmos de verificación facial en GPU. Los resultados en términos de rendimiento han sido altamente satisfactorios, llegando a obtenerse speedups superiores a 200 en comparación con implementaciones paralelas tradicionales (OpenMP). Asimismo se ha desarrollado una interfaz gráfica que permite realizar la verificación de la identidad de una persona apartir de dos fotografías con cualquiera de los métodos implementados. [ABSTRACT] Crime and fraud derived from identy theft produce loss of millions to enterprises and nations. Nowadays there exist several biometric methods for identity verification. One of them is facials recognition, of great practical interest due to its non-instructive character. The algorithms applied to facial verification demand high computational cost, making it difficult to use them in real-time applications. However, these algorithms show a large degree of data-level parallelism which could be exploited with multi-core platforms. One of the main current representatives of multi-core platforms are graphics processing units (GPUs). This project deals with the implementation of several face verification algorithms in GPUs. The performance results were highly satisfactory, reaching speedups of 200 when compared to traditional parallel implementations (OpenMP). Furthermore, a graphical interface that allows performing identity verification of a person with any of the implemented methods was developed

Activating transcription factor 6 derepression mediates neuroprotection in Huntington disease

Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction and neurodegeneration in Huntington disease (HD); however, the factors that disrupt homeostasis are not fully understood. Here, we determined that expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in murine in vivo and in vitro HD models and in HD patients. DREAM downregulation was observed early after birth and was associated with endogenous neuroprotection. In the R6/2 mouse HD model, induced DREAM haplodeficiency or blockade of DREAM activity by chronic administration of the drug repaglinide delayed onset of motor dysfunction, reduced striatal atrophy, and prolonged life span. DREAM-related neuroprotection was linked to an interaction between DREAM and the unfolded protein response (UPR) sensor activating transcription factor 6 (ATF6). Repaglinide blocked this interaction and enhanced ATF6 processing and nuclear accumulation of transcriptionally active ATF6, improving prosurvival UPR function in striatal neurons. Together, our results identify a role for DREAM silencing in the activation of ATF6 signaling, which promotes early neuroprotection in HDThis work was funded by the Instituto de Salud Carlos III/CIBERNED (to J.R. Naranjo, B. Mellström, and A. Rábano), FISS-RIC RD12/0042/0019 (to C. Valenzuela), Madrid regional government/Neurodegmodels (to J.R. Naranjo), MINECO grants SAF2010-21784 and SAF2014-53412-R (to J.R. Naranjo), SAF2012-32209 (to M. Gutierrez-Rodriguez), SAF2010-14916 and SAF2013-45800-R (to C. Valenzuela), and a grant from the Swedish Research Council (J.Y. Li

Human dendritic cells activated with MV130 induce Th1, Th17 and IL-10 responses via RIPK2 and MyD88 signalling pathways

Recurrent respiratory tract infections (RRTIs) are the first leading cause of community-and nosocomial-acquired infections. Antibiotics remain the mainstay of treatment, enhancing the potential to develop antibiotic resistances. Therefore, the development of new alternative approaches to prevent and treat RRTIs is highly demanded. Daily sublingual administration of the whole heat-inactivated polybacterial preparation (PBP) MV130 significantly reduced the rate of respiratory infections in RRTIs patients, however, the immunological mechanisms of action remain unknown. Herein, we study the capacity of MV130 to immunomodulate the function of human dendritic cells (DCs) as a potential mechanism that contribute to the clinical benefits. We demonstrate that DCs from RRTIs patients and healthy controls display similar ex vivo immunological responses to MV130. By combining systems biology and functional immunological approaches we show that MV130 promotes the generation of Th1/Th17 responses via receptor-interacting serine/threonine-protein kinase-2 (RIPK2)-and myeloid-differentiation primary-response gene88 (MyD88)-mediated signalling pathways under the control of IL-10. In vivo BALB/c mice sublingually immunized with MV130 display potent systemic Th1/Th17 and IL-10 responses against related and unrelated antigens. We elucidate immunological mechanisms underlying the potential way of action of MV130, which might help to design alternative treatments in other clinical conditions with high risk of recurrent infections.This work was supported by grant IPT-2012-0639-090000 from INNPACTO and MINECO, Spain to Inmunotek S.L. The authors' laboratories are supported by grants SAF2014-52706-R to O.P. from MINECO, Spain, and SAF2016-79040R to D.S. from MINECO and European Fund for Regional Development, Spain. O.P. is a Ramon y Cajal Scholar funded by MINECO and the European Social Fund. L.C. is a recipient of a European Respiratory Society Fellowship (RESPIRE2-2013-3708). We thank to Juan Lopez-Relano and Sarai Martinez-Cano for excellent technical assistance with mice experiments.S

A study of alterations in DNA epigenetic modifications (5mC and 5hmC) and gene expression influenced by simulated microgravity in human lymphoblastoid cells

Cells alter their gene expression in response to exposure to various environmental changes. Epigenetic mechanisms such as DNA methylation are believed to regulate the alterations in gene expression patterns. In vitro and in vivo studies have documented changes in cellular proliferation, cytoskeletal remodeling, signal transduction, bone mineralization and immune deficiency under the influence of microgravity conditions experienced in space. However microgravity induced changes in the epigenome have not been well characterized. In this study we have used Next-generation Sequencing (NGS) to profile ground-based “simulated” microgravity induced changes on DNA methylation (5-methylcytosine or 5mC), hydroxymethylation (5-hydroxymethylcytosine or 5hmC), and simultaneous gene expression in cultured human lymphoblastoid cells. Our results indicate that simulated microgravity induced alterations in the methylome (~60% of the differentially methylated regions or DMRs are hypomethylated and ~92% of the differentially hydroxymethylated regions or DHMRs are hyperhydroxymethylated). Simulated microgravity also induced differential expression in 370 transcripts that were associated with crucial biological processes such as oxidative stress response, carbohydrate metabolism and regulation of transcription. While we were not able to obtain any global trend correlating the changes of methylation/ hydroxylation with gene expression, we have been able to profile the simulated microgravity induced changes of 5mC over some of the differentially expressed genes that includes five genes undergoing differential methylation over their promoters and twenty five genes undergoing differential methylation over their gene-bodies. To the best of our knowledge, this is the first NGS-based study to profile epigenomic patterns induced by short time exposure of simulated microgravity and we believe that our findings can be a valuable resource for future explorations