A5084403128- Genetic Associations and Epidemiology
- RNA Research and Splicing
- RNA modifications and cancer
- Chemokine receptors and signaling
- RNA and protein synthesis mechanisms
- Cytokine Signaling Pathways and Interactions
- Genomics and Rare Diseases
- Synthesis and biological activity
- Epigenetics and DNA Methylation
- Molecular Biology Techniques and Applications
- Genomics and Chromatin Dynamics
- Single-cell and spatial transcriptomics
- Blood groups and transfusion
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- CRISPR and Genetic Engineering
- Immune cells in cancer
- Inflammatory mediators and NSAID effects
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Genomics and Phylogenetic Studies
- Cerebral Venous Sinus Thrombosis
- Research Data Management Practices
- Ferroptosis and cancer prognosis
- Bioinformatics and Genomic Networks
- Bone and Joint Diseases
Wellcome Sanger Institute
2018-2025
Human Technopole
2023-2024
University of Florida
2017-2020
Centro Nacional de Biotecnología
2013-2018
SIB Swiss Institute of Bioinformatics
2014-2015
Hospital Universitari Germans Trias i Pujol
2014
Hospital Universitario La Paz
2013
Icahn School of Medicine at Mount Sinai
2013
Universidad Complutense de Madrid
2013
Cancer Research Center
2013
High-throughput sequencing of full-length transcripts using long reads has paved the way for discovery thousands novel transcripts, even in well-annotated mammalian species. The advances technology have created a need studies and tools that can characterize these variants. Here, we present SQANTI, an automated pipeline classification long-read assess quality data preprocessing 47 unique descriptors. We apply SQANTI to neuronal mouse transcriptome Pacific Biosciences (PacBio) illustrate how...
Chemokines are relevant molecules in shaping the tumor microenvironment, although their contributions to tumorigenesis not fully understood. We studied influence of chemokine CX3CL1/fractalkine de novo breast cancer formation using HER2/neu transgenic mice. CX3CL1 expression was downmodulated tumors, yet, paradoxically, adenovirus-mediated milieu enhanced mammary numbers a dose-dependent manner. Increased multiplicity consequence CX3CL1-induced metastatic dissemination primary tumor, induced...
Evidence links aryl hydrocarbon receptor (AHR) activation to rheumatoid arthritis (RA) pathogenesis, although results are inconsistent. AHR agonists inhibit pro-inflammatory cytokine expression in macrophages, pivotal cells RA aetiopathogenesis, which hints at specific circuits that regulate the pathway macrophages. We compared microRNA (miR) CD14(+) from patients with active or osteoarthritis (OA). Seven miR were downregulated and one (miR-223) upregulated OA cells. miR-223 upregulation...
Recent advances in long-read sequencing solve inaccuracies alternative transcript identification of full-length transcripts short-read RNA-Seq data, which encourages the development methods for isoform-centered functional analysis. Here, we present tappAS, first framework to enable a comprehensive Functional Iso-Transcriptomics (FIT) analysis, is effective at revealing impact context-specific post-transcriptional regulation. tappAS uses isoform-resolved annotation coding and non-coding...
Abstract Neutrophils play fundamental roles in innate immune response, shape adaptive immunity, and are a potentially causal cell type underpinning genetic associations with system traits diseases. Here, we profile the binding of myeloid master regulator PU.1 primary neutrophils across nearly hundred volunteers. We show that variants associated differential underlie genetically-driven differences count susceptibility to autoimmune inflammatory integrate these results other multi-individual...
Abstract One drawback of chemotherapy is poor drug delivery to tumor cells, due in part hyperpermeability the vasculature. Extracellular superoxide dismutase (SOD3) an antioxidant enzyme usually repressed milieu. Here we show that specific SOD3 re-expression tumor-associated endothelial cells (ECs) increases doxorubicin (Doxo) into and chemotherapeutic effect on tumors. Enhanced activity fostered perivascular nitric oxide accumulation reduced vessel leakage by inducing vascular cadherin...
// Emilia Mira 1 , Lorena Carmona-Rodríguez Manuel Tardáguila Iñigo Azcoitia 2 Alicia González-Martín 1,4 Luis Almonacid Josefina Casas 3 Gemma Fabriás Santos Mañes Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Madrid, Spain, Cell Biology, School Universidad Complutense Biomedicinal Chemistry, Catalan Institute Advanced Chemistry/CSIC, Barcelona, Spain 4 Present address: The Scripps Research Institute, Microbial Science, La Jolla, CA Correspondence: Mañes,...
ABSTRACT High-throughput sequencing of full-length transcripts using long reads has paved the way for discovery thousands novel transcripts, even in very well annotated organisms as mice and humans. Nonetheless, there is a need studies tools that characterize these isoforms. Here we present SQANTI, an automated pipeline classification long-read computes 47 descriptors can be used to assess quality data preprocessing pipelines. We applied SQANTI neuronal mouse transcriptome PacBio illustrate...
Sequencing projects have identified large numbers of rare stop-gain and frameshift variants in the human genome. As most these are observed heterozygous state, they test a gene’s tolerance to haploinsufficiency dominant loss function. We analyzed distribution truncating across 16,260 autosomal protein coding genes 11,546 individuals. 39,893 affecting 12,062 genes, which significantly differed from an expectation 12,916 under model neutral de novo mutation (p<10−4). Extrapolating this...
Gene misexpression is the aberrant transcription of a gene in context where it usually inactive. Despite its known pathological consequences specific rare diseases, we have limited understanding wider prevalence and mechanisms humans. To address this, analyzed 4,568 whole-blood bulk RNA sequencing samples from INTERVAL study blood donors. We found that while individual events occur rarely, aggregate they were almost all third inactive protein-coding genes. Using 2,821 paired whole-genome...
Abstract Previous genome-wide association studies (GWAS) of hematological traits have identified over 10 000 distinct trait-specific risk loci. However, at these loci, the underlying causal mechanisms remain incompletely characterized. To elucidate novel biology and better understand known we performed a transcriptome-wide study (TWAS) 29 in 399 835 UK Biobank (UKB) participants European ancestry using gene expression prediction models trained from whole blood RNA-seq data 922 individuals....
Summary The biological mechanisms through which most non-protein-coding genetic variants affect disease risk are unknown. To investigate the gene-regulatory cascades that ensue from these variants, we mapped blood gene expression and splicing quantitative trait loci (QTLs) bulk RNA-sequencing in 4,732 participants, integrated data with protein, metabolite lipid QTLs same individuals. We identified cis -QTLs for of 17,233 genes 29,514 events (in 6,853 genes). Using colocalization analysis,...
Abstract The identification of causal genetic variants for common diseases improves understanding disease biology. Here we use data from the BLUEPRINT project to identify regulatory quantitative trait loci (QTL) three primary human immune cell types and these fine-map putative twelve immune-mediated diseases. We 340 unique, non major histocompatibility complex (MHC) that colocalise with high (>98%) posterior probability QTLs, apply Bayesian frameworks associations at each locus. show...
Abstract Two decades of Genome Wide Association Studies (GWAS) have yielded hundreds thousands robust genetic associations to human complex traits and diseases. Nevertheless, the dissection functional consequences variants lags behind, especially for non-coding (RNVs). Here we characterised a set rare, with large effects on haematological by integrating (i) massively parallel reporter assay (ii) CRISPR/Cas9 screen (iii) in vivo gene expression transcript relative abundance analysis whole...
Inflammatory mediators can play a dual role in oncogenesis and tumor progression. CX3CL1, chemokine previously implicated natural killer cell- CD8+ T cell-mediated antitumor immune responses, has now been identified as promoter of ERBB2-expressing breast carcinomas it cross-activates members the epidermal growth factor receptor family.
Alternative splicing leverages genomic content by allowing the synthesis of multiple transcripts and, implication, protein isoforms, from a single gene. However, estimating abundance produced in given tissue short sequencing reads is difficult and can result both construction that do not exist, failure to identify true transcripts. An alternative approach catalog events make up isoforms (splice junctions exons). We present here Event Analysis (EA) approach, where we project onto genome...
Abstract Gene misexpression is the aberrant transcription of a gene in context where it usually inactive. Despite its known pathological consequences specific rare diseases, we have limited understanding wider prevalence and mechanisms humans. To address this, analyzed 4,568 whole blood bulk RNA sequencing samples from INTERVAL study donors. We found that while individual events occur rarely, aggregate they were almost all over half inactive genes. Using 2,821 paired genome samples,...
Covalent histone modifications clearly play an essential role in ligand-dependent transcriptional regulation by nuclear receptors. One of the predominant mechanisms used receptors to activate or repress target-gene transcription is recruitment coregulatory factors capable covalently modify amino terminal ends histones. Here we show that thyroid hormone (T3) produces a rapid increase H3Ser10 phosphorylation (H3Ser10ph) concomitant displacement heterochromatin protein 1β (HP1β) periphery....
Abstract Traditionally, the functional analysis of gene expression data has used pathway and network enrichment algorithms. These methods are usually rather than transcript centric hence fall short to unravel roles associated posttranscriptional regulatory mechanisms such as Alternative Splicing (AS) PolyAdenylation (APA), jointly referred here Transcript Processing (AltTP). Moreover, short-read RNA-seq serious limitations resolve full-length transcripts, further complicating study isoform...
A 70-year-old man presented with a 3-day history of nausea, vomiting and constitutional symptoms (fatigue anorexia). During hospitalization he developed diplopia. Cranial magnetic resonance imaging gadolinium (Figure 1a) showed inflammation the entire choroid plexus. diagnosis granulomatosis polyangiitis (GPA) was made based …
Summary Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant health burden. Here we integrate data from UK Biobank large-scale international collaborative effort, including 563,946 European ancestry participants, discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering the full allele frequency spectrum of variation impacting...