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Andres-Leon E.,Bioinformatics Unit UBio | Andres-Leon E.,University of Seville | Pena D.G.,University of Vigo | Gomez-Lopez G.,Bioinformatics Unit UBio | Pisano D.G.,Bioinformatics Unit UBio
Database | Year: 2015

MicroRNAs (miRNAs) are small non-coding elements involved in the post-transcriptional down-regulation of gene expression through base pairing with messenger RNAs (mRNAs). Through this mechanism, several miRNA-mRNA pairs have been described as critical in the regulation ofmultiple cellular processes, including early embryonic development and pathological conditions. Many of these pairs (such as miR-15 b/BCL2 in apoptosis or BART-6/BCL6 in diffuse large B-cell lymphomas) were experimentally discovered and/or computationally predicted. Available tools for target prediction are usually based on sequence matching, thermodynamics and conservation, among other approaches. Nevertheless, the main issue on miRNA-mRNA pair prediction is the little overlapping results among different prediction methods, or even with experimentally validated pairs lists, despite the fact that all rely on similar principles. To circumvent this problem, we have developed miRGate, a database containing novel computational predicted miRNA-mRNA pairs that are calculated using well-established algorithms. In addition, it includes an updated and complete dataset of sequences for both miRNA and mRNAs 30′Untranslated region from human (including human viruses), mouse and rat, as well as experimentally validated data from four well-known databases. The underlying methodology of miRGate has been successfully applied to independent datasets providing predictions that were convincingly validated by functional assays. miRGate is an open resource available at For programmatic access, we have provided a representational state transfer web service application programming interface that allows accessing the database at © The Author(s) 2015. Published by Oxford University Press.

Sanchez-Bailon M.P.,Institute Investigaciones Biomedicas A Sols Csic Uam | Calcabrini A.,Institute Investigaciones Biomedicas A Sols Csic Uam | Calcabrini A.,Instituto Superiore Of Sanita | Gomez-Dominguez D.,Institute Investigaciones Biomedicas A Sols Csic Uam | And 6 more authors.
Cellular Signalling | Year: 2012

SFKs are frequently deregulated in cancer where they control cellular proliferation, migration, survival and metastasis. Here we study the role of SFKs catalytic activity in triple-negative/basal-like and metastatic human breast cancer MDA-MB-231 cells employing three well-established inhibitors: Dasatinib, PP2 and SU6656. These compounds inhibited migration and invasion. Concomitantly, they reduced Fak, paxillin, p130CAS, caveolin-1 phosphorylation and altered cytoskeletal structures. They also inhibited cell proliferation, but in different manners. Dasatinib and PP2 increased p27 Kip1 expression and reduced c-Myc levels, restraining G1-S transition. In contrast, SU6656 did not modify p27 Kip1 expression, slightly altered c-Myc levels and generated polyploid multinucleated cells, indicating inhibition of cytokinesis. These later effects were also observed in SYF fibroblasts, suggesting a SFKs-independent action. ZM447439, an Aurora B kinase inhibitor, produced similar cell cycle and morphological alterations in MDA-MB-231 cells, indicating that SU6656 blocked Aurora B kinase. This was confirmed by inhibition of histone H3 phosphorylation, the canonical Aurora B kinase substrate. Furthermore, hierarchical clustering analysis of gene expression profiles showed that SU6656 defined a set of genes that differed from Dasatinib and PP2. Additionally, Gene Set Enrichment Analyses revealed that SU6656 significantly reduces the Src pathway. Together, these results show the importance of SFKs catalytic activity for MDA-MB-231 proliferation, migration and invasiveness. They also illustrate that SU6656 acts as dual SFKs and Aurora B kinase inhibitor, suggesting its possible use as a therapeutic agent in breast cancer. © 2012 Elsevier Inc..

Fernandez-Ramires R.,Human Genetics Group | Gomez G.,Bioinformatics Unit UBio | Munoz-Repeto I.,Human Genetics Group | De Cecco L.,Fondazione Instituto Nazionale Dei Tumori | And 10 more authors.
International Journal of Cancer | Year: 2011

To better understand the alterations present in the group of the so-called BRCAX tumors, we have used a cDNA microarray containing genes related to tumorigenesis and analyzed a series of 49 tumors consisting of 13 BRCA1, 14 BRCAX and 22 sporadic. We have confirmed that the BRCAX tumors are heterogeneous and can be divided in at least two main subgroups, so-called A and B, transcriptionally distinguishable and with different altered pathways within each of the groups. We have found that BRCAX-A and B subgroups, can be classified as Luminal A and Luminal B, respectively, taking into account the intrinsic phenotypes defined for the sporadic breast tumors. We have found that, at the somatic level, the BRCAX-B tumors are identical to their sporadic Luminal B counterparts, whereas BRCAX-A, despite having a Luminal A phenotype, shows additional genomic alterations. We have found 21 deregulated genes in the BRCAX-A group that we have called "the BRCAX susceptibility pathway" and suggested it as a candidate to search for new genes involved in the inherited susceptibility underlying the disease in this group. © 2010 UICC.

Rubio-Camarillo M.,Structural Computational Biology Group | Gomez-Lopez G.,Bioinformatics Unit UBio | Fernandez J.M.,Spanish National Bioinformatics Institute INB | Valencia A.,Structural Computational Biology Group | And 2 more authors.
Bioinformatics | Year: 2013

Motivation: RUbioSeq has been developed to facilitate the primary and secondary analysis of re-sequencing projects by providing an integrated software suite of parallelized pipelines to detect exome variants (single-nucleotide variants and copy number variations) and to perform bisulfite-seq analyses automatically. RUbioSeq's variant analysis results have been already validated and published. © The Author 2013.

Rubio-Camarillo M.,Bioinformatics Unit UBio | Lopez-Fernandez H.,University of Vigo | Lopez-Fernandez H.,Institute Investigacion Biomedica Of Vigo Ibiv | Gomez-Lopez G.,Bioinformatics Unit UBio | And 7 more authors.
Advances in Intelligent Systems and Computing | Year: 2016

To facilitate routine analysis and to improve the reproducibility of the results, next-generation sequencing analysis requires intuitive, efficient and integrated data processing pipelines. Here, we present RUbioSeq+, a multiplatform application that incorporates a suite of automated and parallelized workflows to analyse NGS data. The software supports DNA-seq (singlenucleotide and copy number variation analyses) as well as for bisulfite-seq and ChIP-seq workflows. RUbioSeq+ supports parallelized and multithreaded execution, and its interactive graphical user interface facilitates its use by both biomedical researchers and bioinformaticians. Results generated by our software have been experimentally validated and accepted for publication. RUbioSeq+ is free and open to all users at © Springer International Publishing Switzerland 2016.

Ambrosio M.R.,University of Siena | Navari M.,University of Siena | Di Lisio L.,Hospital Universitario Marques Of Valdecilla | Leon E.A.,Bioinformatics Unit UBio | And 9 more authors.
Infectious Agents and Cancer | Year: 2014

Background: Burkitt lymphoma is an aggressive B-cell lymphoma presenting in three clinical forms: endemic, sporadic and immunodeficiency-associated. More than 90% of endemic Burkitt lymphoma carry latent Epstein-Barr virus, whereas only 20% of sporadic Burkitt lymphoma are associated with Epstein-Barr infection. Although the Epstein-Barr virus is highly related with the endemic form, how and whether the virus participates in its pathogenesis remains to be fully elucidated. In particular, the virus may impair cellular gene expression by its own encoded microRNAs. Methods. Using microRNA profiling we compared Epstein-Barr-positive and Epstein-Barr-negative Burkitt lymphoma cases for both cellular and viral microRNAs. The array results were validated by qRT-PCR, and potential targets of viral microRNAs were then searched by bioinformatic predictions, and classified in functional categories, according to the Gene Ontology. Our findings were validated by in vitro functional studies and by immunohistochemistry on a larger series of cases. Results: We showed that a few cellular microRNAs are differentially expressed between Epstein-Barr-positive and Epstein-Barr-negative Burkitt lymphoma cases, and identified a subset of viral microRNAs expressed in Epstein-Barr-positive Burkitt lymphomas. Of these, we characterized the effects of viral BART6-3p on regulation of cellular genes. In particular, we analyzed the IL-6 receptor genes (IL-6Rα and IL-6ST), PTEN and WT1 expression for their possible relevance to Burkitt lymphoma. By means of immunohistochemistry, we observed a down-regulation of the IL-6 receptor and PTEN specifically in Epstein-Barr-positive Burkitt lymphoma cases, which may result in the impairment of key cellular pathways and may contribute to malignant transformation. On the contrary, no differences were observed between Epstein-Barr-positive and Epstein-Barr-negative Burkitt lymphoma cases for WT1 expression. Conclusions: Our preliminary results point at an active role for the Epstein-Barr virus in Burkitt lymphomagenesis and suggest new possible mechanisms used by the virus in determining dysregulation of the host cell physiology. © 2014 Ambrosio et al.; licensee BioMed Central Ltd.

PubMed | University of Vigo, Spanish National Bioinformatics Institute INB and Bioinformatics Unit UBio
Type: | Journal: Computer methods and programs in biomedicine | Year: 2016

To facilitate routine analysis and to improve the reproducibility of the results, next-generation sequencing (NGS) analysis requires intuitive, efficient and integrated data processing pipelines.We have selected well-established software to construct a suite of automated and parallelized workflows to analyse NGS data for DNA-seq (single-nucleotide variants (SNVs) and indels), CNA-seq, bisulfite-seq and ChIP-seq experiments.Here, we present RUbioSeq+, an updated and extended version of RUbioSeq, a multiplatform application that incorporates a suite of automated and parallelized workflows to analyse NGS data. This new version includes: (i) an interactive graphical user interface (GUI) that facilitates its use by both biomedical researchers and bioinformaticians, (ii) a new pipeline for ChIP-seq experiments, (iii) pair-wise comparisons (case-control analyses) for DNA-seq experiments, (iv) and improvements in the parallelized and multithreaded execution options. Results generated by our software have been experimentally validated and accepted for publication.RUbioSeq+ is free and open to all users at

Glez-Pena D.,University of Vigo | Gomez-Lopez G.,Bioinformatics Unit UBio | Reboiro-Jato M.,University of Vigo | Fdez-Riverola F.,University of Vigo | Pisano D.G.,Bioinformatics Unit UBio
BMC Bioinformatics | Year: 2011

Background: Genomic position (GP) files currently used in next-generation sequencing (NGS) studies are always difficult to manipulate due to their huge size and the lack of appropriate tools to properly manage them. The structure of these flat files is based on representing one line per position that has been covered by at least one aligned read, imposing significant restrictions from a computational performance perspective.Results: PileLine implements a flexible command-line toolkit providing specific support to the management, filtering, comparison and annotation of GP files produced by NGS experiments. PileLine tools are coded in Java and run on both UNIX (Linux, Mac OS) and Windows platforms. The set of tools comprising PileLine are designed to be memory efficient by performing fast seek on-disk operations over sorted GP files.Conclusions: Our novel toolbox has been extensively tested taking into consideration performance issues. It is publicly available at under the GNU LGPL license. Full documentation including common use cases and guided analysis workflows is available at © 2011 Glez-Peña et al; licensee BioMed Central Ltd.

Lopez-Fernandez H.,University of Vigo | Glez-Pena D.,University of Vigo | Reboiro-Jato M.,University of Vigo | Gomez-Lopez G.,Bioinformatics Unit UBio | And 2 more authors.
Advances in Intelligent and Soft Computing | Year: 2012

AIBench is a Java application framework for building translational software in Biomedicine. In this paper, we show how to use this framework to develop rich user interfaces in next-generation sequencing (NGS) experiments. In particular, we present PileLineGUI, a desktop environment for handling genome position files in next-generation studies based on the PileLine command-line toolbox. © 2012 Springer-Verlag.

Lopez-Fernandez H.,University of Vigo | Glez-Pena D.,University of Vigo | Reboiro-Jato M.,University of Vigo | Gomez-Lopez G.,Bioinformatics Unit UBio | And 2 more authors.
Nucleic Acids Research | Year: 2011

Next-generation sequencing (NGS) technologies are making sequence data available on an unprecedented scale. In this context, new catalogs of Single Nucleotide Polymorphism and mutations generated by resequencing studies are usually stored in genome position files (e.g. Variant Call Format, SAMTools pileup, BED, GFF) comprising of large lists of genomic positions, which are difficult to handle by researchers. Here, we present PileLineGUI, a novel desktop application primarily designed for manipulating, browsing and analysing genome position files (GPF), with specific support to somatic mutation finding studies. The developed tool also integrates a new genome browser module specially designed for inspecting GPFs. PileLineGUI is free, multiplatform and designed to be intuitively used by biomedical researchers. PileLineGUI is available at: © 2011 The Author(s).

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