José María Fernández

iHOP web services

iHOP provides fast, accurate, comprehensive, and up-to-date summary information on more than 80 000 biological molecules by automatically extracting key sentences from millions of PubMed documents. Its intuitive user interface and navigation scheme have made iHOP extremely successful among biologists, counting more than 500 000 visits per month (iHOP access statistics: http://www.ihop-net.org/UniPub/iHOP/info/logs/). Here we describe a public programmatic API that enables the integration of main iHOP functionalities in bioinformatic programs and workflows.

Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells

Summary Characterizing the multifaceted contribution of genetic and epigenetic factors to disease phenotypes is a major challenge in human genetics and medicine. We carried out high-resolution genetic, epigenetic, and transcriptomic profiling in three major human immune cell types (CD14+ monocytes, CD16+ neutrophils, and naive CD4+ T cells) from up to 197 individuals. We assess, quantitatively, the relative contribution of cis-genetic and epigenetic factors to transcription and evaluate their impact as potential sources of confounding in epigenome-wide association studies. Further, we characterize highly coordinated genetic effects on gene expression, methylation, and histone variation through quantitative trait locus (QTL) mapping and allele-specific (AS) analyses. Finally, we demonstrate colocalization of molecular trait QTLs at 345 unique immune disease loci. This expansive, high-resolution atlas of multi-omics changes yields insights into cell-type-specific correlation between diverse genomic inputs, more generalizable correlations between these inputs, and defines molecular events that may underpin complex disease risk.

The EMBRACE web service collection

The EMBRACE (European Model for Bioinformatics Research and Community Education) web service collection is the culmination of a 5-year project that set out to investigate issues involved in developing and deploying web services for use in the life sciences. The project concluded that in order for web services to achieve widespread adoption, standards must be defined for the choice of web service technology, for semantically annotating both service function and the data exchanged, and a mechanism for discovering services must be provided. Building on this, the project developed: EDAM, an ontology for describing life science web services; BioXSD, a schema for exchanging data between services; and a centralized registry (http://www.embraceregistry.net) that collects together around 1000 services developed by the consortium partners. This article presents the current status of the collection and its associated recommendations and standards definitions.

RUbioSeq: a suite of parallelized pipelines to automate exome variation and bisulfite-seq analyses

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. Availability: http://rubioseq.sourceforge.net/. Contact: mrubioc@cnio.es

Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types

BackgroundA healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability.ResultsWe apply a novel analytical approach to measure and compare transcriptional and epigenetic variability genome-wide across CD14+CD16− monocytes, CD66b+CD16+ neutrophils, and CD4+CD45RA+ naïve T cells from the same 125 healthy individuals. We discover substantially increased variability in neutrophils compared to monocytes and T cells. In neutrophils, genes with hypervariable expression are found to be implicated in key immune pathways and are associated with cellular properties and environmental exposure. We also observe increased sex-specific gene expression differences in neutrophils. Neutrophil-specific DNA methylation hypervariable sites are enriched at dynamic chromatin regions and active enhancers.ConclusionsOur data highlight the importance of transcriptional and epigenetic variability for the key role of neutrophils as the first responders to inflammatory stimuli. We provide a resource to enable further functional studies into the plasticity of immune cells, which can be accessed from: http://blueprint-dev.bioinfo.cnio.es/WP10/hypervariability.

iHOP web services family

iHOP provides fast, accurate, comprehensive, and up-to-date summary information on thousands of biological molecules by automatically extracting key sentences from millions of PubMed documents. iHOP web services are providing public programmatic access to all this information since their publication in 2007. This manuscript describes recent improvements on the iHOP web services family and some of the scenarios in which the web services have been applied. Availability. iHOP web services family is documented at its website http://ws.bioinfo.cnio.es/iHOP/

FUN-L: gene prioritization for RNAi screens

MOTIVATION Most biological processes remain only partially characterized with many components still to be identified. Given that a whole genome can usually not be tested in a functional assay, identifying the genes most likely to be of interest is of critical importance to avoid wasting resources. RESULTS Given a set of known functionally related genes and using a state-of-the-art approach to data integration and mining, our Functional Lists (FUN-L) method provides a ranked list of candidate genes for testing. Validation of predictions from FUN-L with independent RNAi screens confirms that FUN-L-produced lists are enriched in genes with the expected phenotypes. In this article, we describe a website front end to FUN-L. AVAILABILITY AND IMPLEMENTATION The website is freely available to use at http://funl.org

Unveiling the molecular basis of disease co-occurrence: towards personalized comorbidity profiles

Comorbidity is an impactful medical problem that is attracting increasing attention in healthcare and biomedical research. However, little is known about the molecular processes leading to the development of a specific disease in patients affected by other conditions. We present a disease interaction network inferred from similarities in patients’ molecular profiles, which significantly recapitulates epidemiologically documented comorbidities, providing the basis for their interpretation at a molecular level. Furthermore, expanding on the analysis of subgroups of patients with similar molecular profiles, our approach discovers comorbidity relations not previously described, implicates distinct genes in such relations, and identifies drugs whose side effects are potentially associated to the observed comorbidities.

RUbioSeq+: A multiplatform application that executes parallelized pipelines to analyse next-generation sequencing data.

BACKGROUND AND OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSIONS RUbioSeq+ is free and open to all users at http://rubioseq.bioinfo.cnio.es/.

RUbioSeq+: An Application that Executes Parallelized Pipelines to Analyse Next-Generation Sequencing Data

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 multi-platform application that incorporates a suite of automated and parallelized workflows to analyse NGS data. The software supports DNA-seq (single-nucleotide 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 http://rubioseq.bioinfo.cnio.es/.