GEPAS, an experiment-oriented pipeline for the analysis of microarray gene expression data

The Gene Expression Profile Analysis Suite, GEPAS, has been running for more than three years. With >76 000 experiments analysed during the last year and a daily average of almost 300 analyses, GEPAS can be considered a well-established and widely used platform for gene expression microarray data analysis. GEPAS is oriented to the analysis of whole series of experiments. Its design and development have been driven by the demands of the biomedical community, probably the most active collective in the field of microarray users. Although clustering methods have obviously been implemented in GEPAS, our interest has focused more on methods for finding genes differentially expressed among distinct classes of experiments or correlated to diverse clinical outcomes, as well as on building predictors. There is also a great interest in CGH-arrays which fostered the development of the corresponding tool in GEPAS: InSilicoCGH. Much effort has been invested in GEPAS for developing and implementing efficient methods for functional annotation of experiments in the proper statistical framework. Thus, the popular FatiGO has expanded to a suite of programs for functional annotation of experiments, including information on transcription factor binding sites, chromosomal location and tissues. The web-based pipeline for microarray gene expression data, GEPAS, is available at http://www.gepas.org. © 2005 Oxford University Press.J.M.V. is supported by the Formacion del Personal Investigador fellowship program from the Ministerio de Educación y Ciencia. L.C. is supported by a fellowship from the Fondo de Investigacion Sanitaria (grant PI020919). P.M. is supported by a grant from Genoma España and Canada Genome.This work is partly supported by grants from Fundación Ramón Areces, Fundació La Caixa, Fundación BBVA and RTICCC from the FI

Ecología y sociedad: gestión del conejo de monte en la Península Ibérica

The European rabbit (Oryctolagus cuniculus) is considered a key species of Mediterranean ecosystems, to which it is native. In 2019, the IUCN reassessed the status of the species to that of threatened in the Iberian Peninsula due to the decline that had experienced its populations during the last decades. Paradoxically, the species has increased its presence in some Iberian areas, being considered a "plague" for damaging crops and infrastructures. Thus, there is debate among managers, farmers and hunters regarding the objectives of rabbit management (i.e., for population control or increase). A plausible hypothesis to explain this paradoxical situation is the existence of two independent evolutionary units recognized by the IUCN as two subspecies (O.c.cuniculus and O.c.algirus). They present well-defined geographical distributions as well as genetic and morphological differences that even led Darwin to consider them different species. In fact, increasing research indicates that both genetic groups are in an advanced process of speciation, suggesting the need to establish different management measures for each one. The general objective of this doctoral thesis is to develop scientific knowledge to understand the situation of the rabbit and its subspecies in the Peninsula and provide optimal management recommendations for this species in its various contexts. To do this, it pays simultaneous attention to two aspects that have barely been explored in the scientific literature to date: the rabbit subspecies and the study of the social dimension related to its management. In general, an interdisciplinary approach is used for this purpose, combining both ecological and sociological studies. The results highlight the existence of notable differences between the rabbit subspecies, which can support an independent management framework and may help to guarantee the conservation of the O.c.algirus. In addition, the results of this doctoral thesis also suggest an apparent disconnection between the social perception of rabbit problems and research-based knowledge, which emphasizes the need to involve all parties in charge of rabbit management in the construction and communication of knowledge. Such an approach can reduce existing conflict and polarization in the management of the species. Regardless of future decisions about where to draw the boundaries between rabbit subspecies, this study emphasizes the need to understand the social and ecological factors under which the species is managed. In addition, this research on subspecies and the social aspects associated with their management, as well as the practical recommendations offered, could be extended to any other species in similar circumstances.El conejo europeo (Oryctolagus cuniculus) es considerada una especie clave de los ecosistemas mediterráneos, de los que es autóctona. En 2019, la UICN reevaluó el estatus de la especie al de amenazada en la Península Ibérica como consecuencia del declive que han experimentado sus poblaciones en las últimas décadas. Paradójicamente, la especie ha aumentado su presencia en algunas zonas de cultivo ibéricas, siendo considerada una "plaga" por dañar cultivos e infraestructuras. Existe pues un debate cada vez mayor entre los gestores, agricultores y cazadores con respecto a los objetivos de gestion del conejo (es decir, para el control o aumento de la población). Una hipótesis plausible para explicar esta paradójica situación es la existencia de dos unidades evolutivas independientes reconocidas por la UICN como dos subespecies (O.c.cuniculus y O.c.algirus). Presentan distribuciones geográficas bien definidas así como diferencias genéticas y morfológicas que incluso llevaron a Darwin a considerarlas especies distintas. De hecho, cada vez más investigaciones señalan que ambos grupos genéticos se encuentran en un proceso avanzado de especiación, lo que sugiere la necesidad de establecer diferentes medidas de gestión para cada uno. El objetivo general de esta tesis doctoral es desarrollar conocimiento científico que ayude a comprender la situación del conejo y de sus subespecies en la Península con el fin de proporcionar recomendaciones de gestión óptimas para esta especie en sus diversos contextos. Para ello, presta atención simultánea a dos aspectos escasamente explorados en la literatura científica hasta la fecha: las subespecies des de conejo y el estudio de la dimensión social relativa a su gestión. En general, con este fin se emplea un enfoque interdisciplinar que combina estudios tanto ecológicos como sociológicos. Los resultados destacan la existencia de diferencias notables entre las subespecies de conejo, lo que puede apoyar la necesidad de un manejo independiente que garantice la conservación de O.c.algirus. Además, los resultados de esta tesis doctoral también sugieren una aparente desconexión entre la percepción social que se tiene sobre los problemas del conejo y el conocimiento basado en la investigación, lo que enfatiza la necesidad de involucrar a todas las partes encargadas de la gestión del conejo en la construcción y comunicación del conocimiento. Tal enfoque puede reducir el conflicto existente y la polarización en la gestión de la especie. Independientemente de las decisiones futuras sobre dónde trazar los límites entre las subespecies de conejo, este estudio enfatiza la necesidad de comprender los factores sociales y ecológicos en los que se gestiona la especie. En general, las investigaciones sobre las subespecies y los aspectos sociales asociados a su gestión, así como las recomendaciones prácticas que se ofrecen, podrían extenderse a cualquier otra especie en circunstancias similares

Identification of conserved domains in the promoter regions of nitric oxide synthase 2: implications for the species-specific transcription and evolutionary differences

<p>Abstract</p> <p>Background</p> <p>The majority of the genes involved in the inflammatory response are highly conserved in mammals. These genes are not significantly expressed under normal conditions and are mainly regulated at the transcription and prost-transcriptional level. Transcription from the promoters of these genes is very dependent on NF-κB activation, which integrates the response to diverse extracellular stresses. However, in spite of the high conservation of the pattern of promoter regulation in κB-regulated genes, there is inter-species diversity in some genes. One example is nitric oxide synthase 2 (NOS-2), which exhibits a species-specific pattern of expression in response to infection or pro-inflammatory challenge.</p> <p>Results</p> <p>We have conducted a comparative genomic analysis of NOS-2 with different bioinformatic approaches. This analysis shows that in the NOS-2 gene promoter the position and the evolutionary divergence of some conserved regions are different in rodents and non-rodent mammals, and in particular in primates. Two not previously described distal regions in rodents that are similar to the unique upstream region responsible of the NF-κB activation of NOS-2 in humans are fragmented and translocated to different locations in the rodent promoters. The rodent sequences moreover lack the functional κB sites and IFN-γ response sites present in the homologous human, rhesus monkey and chimpanzee regions. The absence of κB binding in these regions was confirmed by electrophoretic mobility shift assays.</p> <p>Conclusion</p> <p>The data presented reveal divergence between rodents and other mammals in the location and functionality of conserved regions of the NOS-2 promoter containing NF-κB and IFN-γ response elements.</p

Exploring the reasons for the large density of triplex-forming oligonucleotide target sequences in the human regulatory regions

BACKGROUND: DNA duplex sequences that can be targets for triplex formation are highly over-represented in the human genome, especially in regulatory regions. RESULTS: Here we studied using bioinformatics tools several properties of triplex target sequences in an attempt to determine those that make these sequences so special in the genome. CONCLUSION: Our results strongly suggest that the unique physical properties of these sequences make them particularly suitable as "separators" between protein-recognition sites in the promoter region

BABELOMICS: a suite of web tools for functional annotation and analysis of groups of genes in high-throughput experiments

We present Babelomics, a complete suite of web tools for the functional analysis of groups of genes in high-throughput experiments, which includes the use of information on Gene Ontology terms, interpro motifs, KEGG pathways, Swiss-Prot keywords, analysis of predicted transcription factor binding sites, chromosomal positions and presence in tissues with determined histological characteristics, through five integrated modules: FatiGO (fast assignment and transference of information), FatiWise, transcription factor association test, GenomeGO and tissues mining tool, respectively. Additionally, another module, FatiScan, provides a new procedure that integrates biological information in combination with experimental results in order to find groups of genes with modest but coordinate significant differential behaviour. FatiScan is highly sensitive and is capable of finding significant asymmetries in the distribution of genes of common function across a list of ordered genes even if these asymmetries were not extreme. The strong multiple-testing nature of the contrasts made by the tools is taken into account. All the tools are integrated in the gene expression analysis package GEPAS. Babelomics is the natural evolution of our tool FatiGO (which analysed almost 22 000 experiments during the last year) to include more sources on information and new modes of using it. Babelomics can be found at

Computational approaches to study transcriptional regulation in the human genome

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 22-02-200

SpeCond: a method to detect condition-specific gene expression

Transcriptomic studies routinely measure expression levels across numerous conditions. These datasets allow identification of genes that are specifically expressed in a small number of conditions. However, there are currently no statistically robust methods for identifying such genes. Here we present SpeCond, a method to detect condition-specific genes that outperforms alternative approaches. We apply the method to a dataset of 32 human tissues to determine 2,673 specifically expressed genes. An implementation of SpeCond is freely available as a Bioconductor package at http://www.bioconductor.org/packages/release/bioc/html/SpeCond.html

PupasView: a visual tool for selecting suitable SNPs, with putative pathological effect in genes, for genotyping purposes

We have developed a web tool, PupasView, for the selection of single nucleotide polymorphisms (SNPs) with potential phenotypic effect. PupasView constitutes an interactive environment in which functional information and population frequency data can be used as sequential filters over linkage disequilibrium parameters to obtain a final list of SNPs optimal for genotyping purposes. PupasView is the first resource that integrates phenotypic effects caused by SNPs at both the translational and the transcriptional level. PupasView retrieves SNPs that could affect conserved regions that the cellular machinery uses for the correct processing of genes (intron/exon boundaries or exonic splicing enhancers), predicted transcription factor binding sites and changes in amino acids in the proteins for which a putative pathological effect is calculated. The program uses the mapping of SNPs in the genome provided by Ensembl. PupasView will be of much help in studies of multifactorial disorders, where the use of functional SNPs will increase the sensitivity of the identification of the genes responsible for the disease. The PupasView web interface is accessible through and through