Systems Biology Perspectives for Studying Neurodevelopmental Events

Brain development follows a complex process orchestrated by diverse molecular and cellular events for which a perturbation can cause pathologies. In fact, multiple neuronal cell fate decisions driven by complex gene regulatory programs are involved in neurogenesis and neurodevelopment, and their characterization are part of the current challenges on neurobiology. In this chapter, we provide an overview of the various genomic strategies in use to explore the spatiotemporally defined gene regulatory wires implicated in brain development. Finally, we will discuss the intake of these approaches for understanding the multifactorial events implicated in neurodevelopment and the future requirements for further expanding our understanding of the brain

A comprehensive resource for retrieving, visualizing, and integrating functional genomics data

The enormous amount of freely accessible functional genomics data is an invaluable resource for interrogating the biological function of multiple DNA-interacting players and chromatin modifications by large-scale comparative analyses. However, in practice, interrogating large collections of public data requires major efforts for (i) reprocessing available raw reads, (ii) incorporating quality assessments to exclude artefactual and low-quality data, and (iii) processing data by using high-performance computation. Here, we present qcGenomics, a user-friendly online resource for ultrafast retrieval, visualization, and comparative analysis of tens of thousands of genomics datasets to gain new functional insight from global or focused multidimensional data integration.\ua0\ua9 2019 Blum et al

Characterising ChIP-seq binding patterns by model-based peak shape deconvolution

BACKGROUND: Chromatin immunoprecipitation combined with massive parallel sequencing (ChIP-seq) is widely used to study protein-chromatin interactions or chromatin modifications at genome-wide level. Sequence reads that accumulate locally at the genome (peaks) reveal loci of selectively modified chromatin or specific sites of chromatin-binding factors. Computational approaches (peak callers) have been developed to identify the global pattern of these sites, most of which assess the deviation from background by applying distribution statistics. RESULTS: We have implemented MeDiChISeq, a regression-based approach, which--by following a learning process--defines a representative binding pattern from the investigated ChIP-seq dataset. Using this model MeDiChISeq identifies significant genome-wide patterns of chromatin-bound factors or chromatin modification. MeDiChISeq has been validated for various publicly available ChIP-seq datasets and extensively compared with other peak callers. CONCLUSIONS: MeDiChI-Seq has a high resolution when identifying binding events, a high degree of peak-assessment reproducibility in biological replicates, a low level of false calls and a high true discovery rate when evaluated in the context of gold-standard benchmark datasets. Importantly, this approach can be applied not only to 'sharp' binding patterns--like those retrieved for transcription factors (TFs)--but also to the broad binding patterns seen for several histone modifications. Notably, we show that at high sequencing depths, MeDiChISeq outperforms other algorithms due to its powerful peak shape recognition capacity which facilitates discerning significant binding events from spurious background enrichment patterns that are enhanced with increased sequencing depths

Nucleic Acids Res

The absence of a quality control (QC) system is a major weakness for the comparative analysis of genome-wide profiles generated by next-generation sequencing (NGS). This concerns particularly genome binding/occupancy profiling assays like chromatin immunoprecipitation (ChIP-seq) but also related enrichment-based studies like methylated DNA immunoprecipitation/methylated DNA binding domain sequencing, global run on sequencing or RNA-seq. Importantly, QC assessment may significantly improve multidimensional comparisons that have great promise for extracting information from combinatorial analyses of the global profiles established for chromatin modifications, the bindings of epigenetic and chromatin-modifying enzymes/machineries, RNA polymerases and transcription factors and total, nascent or ribosome-bound RNAs. Here we present an approach that associates global and local QC indicators to ChIP-seq data sets as well as to a variety of enrichment-based studies by NGS. This QC system was used to certify >5600 publicly available data sets, hosted in a database for data mining and comparative QC analyses

RARb agonist drug (C286) demonstrates efficacy in a pre-clinical neuropathic pain model restoring multiple pathways via DNA repair mechanisms

Neuropathic pain (NP) is associated with profound gene expression alterations within the nociceptive system. DNA mechanisms, such as epigenetic remodelling and repair pathways have been implicated in NP. Here we have used a rat model of peripheral nerve injury to study the effect of a recently developed RARb agonist, C286, currently under clinical research, in NP. A four week treatment initiated two days after the injury normalised pain sensation. Genome-wide and pathway enrichment analysis showed that multiple mechanisms persistently altered in the spinal cord were restored to preinjury levels by the agonist. Concomitant upregulation of DNA repair proteins, ATM and BRCA1, the latter being required for C286 mediated pain modulation, suggest that early DNA repair may be important to prevent phenotypic epigenetic imprints in NP. Thus, C286 is a promising drug candidate for neuropathic pain and DNA repair mechanisms may be useful therapeutic targets to explore

Monitorización y seguimiento del esfuerzo realizado por los estudiantes y de su asistencia a actividades presenciales

Este artículo documenta el planteamiento, la metodología y los primeros resultados de un plan de monitorización detallada del esfuerzo y de asistencia a actividades presenciales por parte de los estudiantes de las titulaciones ofertadas por la Escuela Técnica Superior de Ingenieros Navales de la Universidad Politécnica de Madrid durante el segundo cuatrimestre del curso 2011-2012. Se ha establecido un sistema mecánico de recogida de datos de esfuerzo por parte de los estudiantes utilizando una hoja tipo test especialmente configurada al efecto. Se pasa una hoja en todas y cada una de las actividades presenciales realizadas y en la hoja se solicita información sobre el trabajo "fuera de clase". Se documenta en este artículo cómo se ha estructurado esa hoja, qué tipo de datos se recogen, cómo se tratan mediante una base de datos creada al efecto, qué tipo de análisis se puede realizar y qué resultados preliminares obtenemos de dichos análisis

Gestión del conocimiento. Perspectiva multidisciplinaria. Volumen 5

El libro “Gestión del Conocimiento. Perspectiva Multidisciplinaria”, Volumen 5, de la Colección Unión Global, es resultado de investigaciones. Los capítulos del libro, son resultados de investigaciones desarrolladas por sus autores. El libro es una publicación internacional, seriada, continua, arbitrada de acceso abierto a todas las áreas del conocimiento, que cuenta con el esfuerzo de investigadores de varios países del mundo, orientada a contribuir con procesos de gestión del conocimiento científico, tecnológico y humanístico que consoliden la transformación del conocimiento en diferentes escenarios, tanto organizacionales como universitarios, para el desarrollo de habilidades cognitivas del quehacer diario. La gestión del conocimiento es un camino para consolidar una plataforma en las empresas públicas o privadas, entidades educativas, organizaciones no gubernamentales, ya sea generando políticas para todas las jerarquías o un modelo de gestión para la administración, donde es fundamental articular el conocimiento, los trabajadores, directivos, el espacio de trabajo, hacia la creación de ambientes propicios para el desarrollo integral de las instituciones

Gestión del conocimiento. Perspectiva multidisciplinaria. Volumen 8

El libro “Gestión del Conocimiento. Perspectiva Multidisciplinaria”, volumen 8, de la Colección Unión Global, es resultado de investigaciones. Los capítulos del libro, son resultados de investigaciones desarrolladas por sus autores. El libro es una publicación internacional, seriada, continua, arbitrada de acceso abierto a todas las áreas del conocimiento, que cuenta con el esfuerzo de investigadores de varios países del mundo, orientada a contribuir con procesos de gestión del conocimiento científico, tecnológico y humanístico que consoliden la transformación del conocimiento en diferentes escenarios, tanto organizacionales como universitarios, para el desarrollo de habilidades cognitivas del quehacer diario. La gestión del conocimiento es un camino para consolidar una plataforma en las empresas públicas o privadas, entidades educativas, organizaciones no gubernamentales, ya sea generando políticas para todas las jerarquías o un modelo de gestión para la administración, donde es fundamental articular el conocimiento, los trabajadores, directivos, el espacio de trabajo, hacia la creación de ambientes propicios para el desarrollo integral de las instituciones

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)