TY - JOUR T1 - Web-based network analysis and visualization using CellMaps. JF - Bioinformatics Y1 - 2016 A1 - Salavert, Francisco A1 - García-Alonso, Luz A1 - Sánchez, Rubén A1 - Alonso, Roberto A1 - Bleda, Marta A1 - Medina, Ignacio A1 - Dopazo, Joaquin KW - Biochemical Phenomena KW - Internet KW - Software AB -

UNLABELLED: : CellMaps is an HTML5 open-source web tool that allows displaying, editing, exploring and analyzing biological networks as well as integrating metadata into them. Computations and analyses are remotely executed in high-end servers, and all the functionalities are available through RESTful web services. CellMaps can easily be integrated in any web page by using an available JavaScript API.

AVAILABILITY AND IMPLEMENTATION: The application is available at: http://cellmaps.babelomics.org/ and the code can be found in: https://github.com/opencb/cell-maps The client is implemented in JavaScript and the server in C and Java.

CONTACT: jdopazo@cipf.es

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

VL - 32 IS - 19 U1 - https://www.ncbi.nlm.nih.gov/pubmed/27296979?dopt=Abstract ER - TY - JOUR T1 - A web tool for the design and management of panels of genes for targeted enrichment and massive sequencing for clinical applications. JF - Nucleic acids research Y1 - 2014 A1 - Alemán, Alejandro A1 - Garcia-Garcia, Francisco A1 - Medina, Ignacio A1 - Joaquín Dopazo KW - Diagnostic KW - Targeted enrichment sequencing KW - WES AB - Disease targeted sequencing is gaining importance as a powerful and cost-effective application of high throughput sequencing technologies to the diagnosis. However, the lack of proper tools to process the data hinders its extensive adoption. Here we present TEAM, an intuitive and easy-to-use web tool that fills the gap between the predicted mutations and the final diagnostic in targeted enrichment sequencing analysis. The tool searches for known diagnostic mutations, corresponding to a disease panel, among the predicted patient’s variants. Diagnostic variants for the disease are taken from four databases of disease-related variants (HGMD-public, HUMSAVAR, ClinVar and COSMIC.) If no primary diagnostic variant is found, then a list of secondary findings that can help to establish a diagnostic is produced. TEAM also provides with an interface for the definition of and customization of panels, by means of which, genes and mutations can be added or discarded to adjust panel definitions. TEAM is freely available at: http://team.babelomics.org. VL - 42 UR - http://nar.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=24861626 ER - TY - JOUR T1 - A web-based interactive framework to assist in the prioritization of disease candidate genes in whole-exome sequencing studies. JF - Nucleic acids research Y1 - 2014 A1 - Alemán, Alejandro A1 - Garcia-Garcia, Francisco A1 - Salavert, Francisco A1 - Medina, Ignacio A1 - Joaquín Dopazo KW - NGS. prioritization AB - Whole-exome sequencing has become a fundamental tool for the discovery of disease-related genes of familial diseases and the identification of somatic driver variants in cancer. However, finding the causal mutation among the enormous background of individual variability in a small number of samples is still a big challenge. Here we describe a web-based tool, BiERapp, which efficiently helps in the identification of causative variants in family and sporadic genetic diseases. The program reads lists of predicted variants (nucleotide substitutions and indels) in affected individuals or tumor samples and controls. In family studies, different modes of inheritance can easily be defined to filter out variants that do not segregate with the disease along the family. Moreover, BiERapp integrates additional information such as allelic frequencies in the general population and the most popular damaging scores to further narrow down the number of putative variants in successive filtering steps. BiERapp provides an interactive and user-friendly interface that implements the filtering strategy used in the context of a large-scale genomic project carried out by the Spanish Network for Research in Rare Diseases (CIBERER) in which more than 800 exomes have been analyzed. BiERapp is freely available at: http://bierapp.babelomics.org/ VL - 42 UR - http://nar.oxfordjournals.org/content/42/W1/W88 ER - TY - JOUR T1 - Whole-genome bisulfite DNA sequencing of a DNMT3B mutant patient. JF - Epigenetics Y1 - 2012 A1 - Heyn, Holger A1 - Vidal, Enrique A1 - Sayols, Sergi A1 - Sanchez-Mut, Jose V A1 - Moran, Sebastian A1 - Medina, Ignacio A1 - Sandoval, Juan A1 - Simó-Riudalbas, Laia A1 - Szczesna, Karolina A1 - Huertas, Dori A1 - Gatto, Sole A1 - Matarazzo, Maria R A1 - Dopazo, Joaquin A1 - Esteller, Manel KW - B-Lymphocytes KW - Cell Line, Transformed KW - Child, Preschool KW - DNA (Cytosine-5-)-Methyltransferases KW - DNA Methylation KW - Epigenesis, Genetic KW - Face KW - Female KW - Genome, Human KW - High-Throughput Nucleotide Sequencing KW - Humans KW - Immunologic Deficiency Syndromes KW - mutation KW - Primary Immunodeficiency Diseases KW - Sequence Analysis, DNA KW - Sulfites AB -

The immunodeficiency, centromere instability and facial anomalies (ICF) syndrome is associated to mutations of the DNA methyl-transferase DNMT3B, resulting in a reduction of enzyme activity. Aberrant expression of immune system genes and hypomethylation of pericentromeric regions accompanied by chromosomal instability were determined as alterations driving the disease phenotype. However, so far only technologies capable to analyze single loci were applied to determine epigenetic alterations in ICF patients. In the current study, we performed whole-genome bisulphite sequencing to assess alteration in DNA methylation at base pair resolution. Genome-wide we detected a decrease of methylation level of 42%, with the most profound changes occurring in inactive heterochromatic regions, satellite repeats and transposons. Interestingly, transcriptional active loci and ribosomal RNA repeats escaped global hypomethylation. Despite a genome-wide loss of DNA methylation the epigenetic landscape and crucial regulatory structures were conserved. Remarkably, we revealed a mislocated activity of mutant DNMT3B to H3K4me1 loci resulting in hypermethylation of active promoters. Functionally, we could associate alterations in promoter methylation with the ICF syndrome immunodeficient phenotype by detecting changes in genes related to the B-cell receptor mediated maturation pathway.

VL - 7 IS - 6 U1 - https://www.ncbi.nlm.nih.gov/pubmed/22595875?dopt=Abstract ER -