David Gomez-Cabrero

David Gomez-Cabrero
Navarrabiomed · Translational Bioinformatics

PhD

About

219
Publications
32,091
Reads
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5,907
Citations
Additional affiliations
May 2017 - present
Navarrabiomed
Position
  • Head of Department
September 2016 - present
King's College London
Position
  • Professor (Associate)
September 2014 - August 2018
Karolinska Institutet
Position
  • Professor (Assistant)

Publications

Publications (219)
Preprint
Recent progress in Single-Cell Genomics have produced different library protocols and techniques for profiling of one or more data modalities in individual cells. Machine learning methods have separately addressed specific integration challenges (libraries, samples, paired-unpaired data modalities). We formulate an unifying data-driven methodology...
Article
Full-text available
Understanding the regulation of normal and malignant human hematopoiesis requires comprehensive cell atlas of the hematopoietic stem cell (HSC) regulatory microenvironment. Here, we develop a tailored bioinformatic pipeline to integrate public and proprietary single-cell RNA sequencing (scRNA-seq) datasets. As a result, we robustly identify for the...
Article
Full-text available
Multiple Sclerosis (MS), the leading cause of non-traumatic neurological disability in young adults, is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS). Due to the poor accessibility to the target organ, CNS-confined processes underpinning the later progressive form of MS remain elusive thereby limiting trea...
Preprint
Aims In this work we investigated the embryonic origin of coronary arterio-ventricular connections, known as coronary artery fistulas (CAF), a congenital heart disease associated to postnatal and adult changes in systemic hemodynamics that may cause cardiac ischemia. Methods and results we have used different animal models (mouse and avian embryos...
Article
Full-text available
PurposeObjective markers of usual diet are of interest as alternative or validating tools in nutritional epidemiology research. The main purpose of the work was to assess whether saliva protein composition can reflect dietary habits in older adults, and how type 2 diabetes impacted on the saliva-diet correlates.Methods214 participants were selected...
Preprint
Full-text available
Early detection has proven to be the most effective strategy to reduce the incidence and mortality of colorectal cancer (CRC). Nevertheless, most current screening programs suffer from low participation rates. A blood test may improve both the adherence to screening and the selection to colonoscopy. In this study, we conducted a serum-based discove...
Article
Background: The putative involvement of chromatin states in multiple sclerosis (MS) is thus far unclear. Here we determined the association of chromatin-accessibility with concurrent genetic, epigenetic and transcriptional events. Material & methods: We generated paired assay for transposase-accessible chromatin sequencing and RNA-seq profiles from...
Preprint
Understanding the regulation of normal and malignant human hematopoiesis requires comprehensive cell atlas of the hematopoietic stem cell (HSC) regulatory microenvironment. Here, we develop a tailored bioinformatic pipeline to integrate public and proprietary single-cell RNA sequencing (scRNA-seq) datasets. As a result, we robustly identify for the...
Preprint
Full-text available
Background Profiling of mRNA expression is an important method to identify biomarkers but complicated by limited correlations between mRNA expression and protein abundance. We hypothesized that these correlations could be improved by mathematical models based on measuring splice variants and time delay in protein translation. Methods We characteriz...
Preprint
Full-text available
PARAGRAPH Fanconi anemia (FA) is a monogenic inherited disease associated with mutations in genes that encode for proteins participating in the FA/BRCA DNA repair pathway. Mutations in FA genes result in chromosomal instability and cell death, leading to cancer risks and progressive cell mortality, most notably in hematopoietic stem and progenitor...
Preprint
Objectives Production of anti-citrullinated peptide/protein antibodies (ACPA) is characteristic for rheumatoid arthritis (RA) and may inform about biological pathways involved in disease development in specific subgroups. Since multiple loci in genome wide association screens have been implicated in RA risk, we investigated the association between...
Article
Full-text available
GM-CSF produced by autoreactive CD4-positive T helper cells is involved in the pathogenesis of autoimmune diseases, such as multiple sclerosis. However, the molecular regulators that establish and maintain the features of GM-CSF-positive CD4 T cells are unknown. In order to identify these regulators, we isolated human GM-CSF-producing CD4 T cells f...
Preprint
Full-text available
Background Multiple Sclerosis (MS), the leading cause of non-traumatic neurological disability in young adults, is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS). Due to the poor accessibility to the target organ, CNS-confined processes underpinning the later progressive form of MS remain elusive thereby li...
Article
Full-text available
During the last decade, extensive efforts have been made to comprehend cardiac cell genetic and functional diversity. Such knowledge allows for the definition of the cardiac cellular interactome as a reasonable strategy to increase our understanding of the normal and pathologic heart. Previous experimental approaches including cell lineage tracing,...
Article
Full-text available
Background While programmed cell death receptor 1 (PD-1) blockade treatment has revolutionized treatment of patients with melanoma, clinical outcomes are highly variable, and only a fraction of patients show durable responses. Therefore, there is a clear need for predictive biomarkers to select patients who will benefit from the treatment. Method...
Preprint
Full-text available
The role of gut microbiota in humans is of great interest, and metagenomics provided the possibilities for extensively analysing bacterial diversity in health and disease. Here we explored the human gut microbiome samples across 19 countries, performing compositional, functional and integrative analysis. To complement these data and analyse the sta...
Article
Full-text available
Technologies for profiling samples using different omics platforms have been at the forefront since the human genome project. Large-scale multi-omics data hold the promise of deciphering different regulatory layers. Yet, while there is a myriad of bioinformatics tools, each multi-omics analysis appears to start from scratch with an arbitrary decisi...
Article
Phenotype-specific omic expression patterns in people with frailty could provide invaluable insight into the underlying multi-systemic pathological processes and targets for intervention. Classical approaches to frailty have not considered the potential for different frailty phenotypes. We characterized associations between frailty (with/without di...
Article
Phenotype-specific omic expression patterns in people with frailty could provide invaluable insight into the underlying multi-systemic pathological processes and targets for intervention. Classical approaches to frailty have not considered the potential for different frailty phenotypes. We characterized associations between frailty (with/without di...
Preprint
Full-text available
Single-cell multi-omics technologies enable profiling of several data-modalities from the same cell. We designed LIBRA, a Neural Network based framework, for learning translations between paired multi-omics profiles into a shared latent space. We demonstrate LIBRA to be state-of-the-art for multi-omics clustering. In addition, LIBRA is more robust...
Preprint
Full-text available
Recent progress in single-cell genomics has generated multiple tools for cell clustering, annotation, and trajectory inference; yet, inferring their associated regulatory mechanisms is unresolved. Here we present scMomentum, a model-based data-driven formulation to predict gene regulatory networks and energy landscapes from single-cell transcriptom...
Preprint
Full-text available
Technologies for profiling samples using different omics platforms have been at the forefront since the human genome project. Large-scale multi-omics data hold the promise of deciphering different regulatory layers. Yet, while there is a myriad of bioinformatics tools, each multi-omics analysis appears to start from scratch with an arbitrary decisi...
Article
Full-text available
Background: Gene-set analysis tools, which make use of curated sets of molecules grouped based on their shared functions, aim to identify which gene-sets are over-represented in the set of features that have been associated with a given trait of interest. Such tools are frequently used in gene-centric approaches derived from RNA-sequencing or micr...
Article
Full-text available
Background: Cardiac fibroblasts (CFs) have a central role in the ventricular remodeling process associated with different types of fibrosis. Recent studies have shown that fibroblasts do not respond homogeneously to heart injury. Because of the limited set of bona fide fibroblast markers, a proper characterization of fibroblast population heteroge...
Article
Background: There is growing evidence that the Mediterranean (Medi) diet may lower the risk of type 2 diabetes mellitus (T2DM). Whether this association is due to the Medi diet by itself or is mediated by a diet -associated lower rate of overweight is uncertain. Our aim was to disentangle these relationships among UK adults. Methods: Based on 21...
Preprint
Full-text available
Until recently, the contribution of bacteriophages to the composition and function of the human microbiome has been largely overlooked. Recent developments in discovering novel bacteriophages from human metagenomes have been mostly focused on the gut. Here we profile and compare the phageome of 633 human oral sites and 221 paired gut phageomes acqu...
Article
Full-text available
Multi-omic studies combine measurements at different molecular levels to build comprehensive models of cellular systems. The success of a multi-omic data analysis strategy depends largely on the adoption of adequate experimental designs, and on the quality of the measurements provided by the different omic platforms. However, the field lacks a comp...
Article
Patients with congenital adrenal hyperplasia (CAH) are at risk of long-term cognitive and metabolic sequelae with some of the effects being attributed to the chronic glucocorticoid treatment that they receive. Our pilot study investigates genome-wide DNA methylation in patients with CAH to determine whether there is preliminary evidence for epigeno...
Article
Background & aims: Acute-on-chronic liver failure (ACLF) is a newly described syndrome, which develops in patients with acute decompensation of cirrhosis, and is characterized by intense systemic inflammation, multiple organ failures and high short-term mortality. The profile of circulating lipid mediators, which are endogenous signaling molecules...
Article
Full-text available
Peripheral arterial disease (PAD) is associated with a high risk of cardiovascular events and death and is postulated to be a critical socioeconomic cost in the future. Extracellular vesicles (EVs) have emerged as potential candidates for new biomarker discovery related to their protein and nucleic acid cargo. In search of new prognostic and therap...
Article
Full-text available
The global threat of antimicrobial resistance has driven the use of high-throughput sequencing techniques to monitor the profile of resistance genes, known as the resistome, in microbial populations. The human oral cavity contains a poorly explored reservoir of these genes. Here we analyse and compare the resistome profiles of 788 oral cavities wor...
Article
Full-text available
Dysregulation of the kynurenine pathway has been regarded as a mechanism of tumor immune escape by the enzymatic activity of indoleamine 2, 3 dioxygenase and kynurenine production. However, the immune-modulatory properties of other kynurenine metabolites such as kynurenic acid, 3-hydroxykynurenine, and anthranilic acid are poorly understood. In thi...
Poster
Full-text available
Background/Purpose: Big data are defined as data sets that are too large or complex for traditional data-processing application software to adequately deal with. Artifcial Intelligence (AI) includes various statistical techniques which can deal with big data. The current use of these concepts in publications related to rheumatic and musculoskeletal...
Article
Full-text available
Rapid advances in single-cell assays have outpaced methods for analysis of those data types. Different single-cell assays show extensive variation in sensitivity and signal to noise levels. In particular, scATAC-seq generates extremely sparse and noisy datasets. Existing methods developed to analyze this data require cells amenable to pseudo-time a...
Article
Full-text available
Multi-omics approaches use a diversity of high-throughput technologies to profile the different molecular layers of living cells. Ideally, the integration of this information should result in comprehensive systems models of cellular physiology and regulation. However, most multi-omics projects still include a limited number of molecular assays and...
Preprint
Full-text available
Background: Patients with congenital adrenal hyperplasia (CAH) are at risk of long-term cognitive and metabolic sequelae. This study investigates genome-wide DNA methylation in patients with CAH to determine whether there is evidence for epigenomic reprogramming as well as any relationship to patient outcome. Methods: We analysed CD4+ T cell DNA fr...
Conference Paper
Full-text available
Background/Purpose: Big data are defined as data sets that are too large or complex for traditional data-processing application software to adequately deal with. Artificial Intelligence (AI) includes various statistical techniques which can deal with big data. The current use of these concepts in publications related to rheumatic and musculoskeleta...
Article
We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of met...
Article
Full-text available
Background: A poor fat-soluble micronutrient (FMN) and a high oxidative stress status are associated with frailty. Our aim was to determine the cross-sectional association of FMNs and oxidative stress biomarkers [protein carbonyls (PrCarb) and 3-nitrotyrosine] with the frailty status in participants older than 65 years. Methods: Plasma levels of...
Article
Full-text available
Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system with prominent neurodegenerative components. The triggering and progression of MS is associated with transcriptional and epigenetic alterations in several tissues, including peripheral blood. The combined influence of transcriptional and epigenetic changes associated wit...
Article
Full-text available
Dimethyl fumarate (DMF) is a first-line-treatment for relapsing-remitting multiple sclerosis (RRMS). The redox master regulator Nrf2, essential for redox balance, is a target of DMF, but its precise therapeutic mechanisms of action remain elusive. Here we show impact of DMF on circulating monocytes and T cells in a prospective longitudinal RRMS pat...
Article
Full-text available
Objective To assess the current use of big data and artificial intelligence (AI) in the field of rheumatic and musculoskeletal diseases (RMDs). Methods A systematic literature review was performed in PubMed MEDLINE in November 2018, with key words referring to big data, AI and RMDs. All original reports published in English were analysed. A mirror...
Preprint
Full-text available
Multi-omics approaches use a diversity of high-throughput technologies to profile the different molecular layers of living cells. Ideally, the integration of this information should result in comprehensive systems models of cellular physiology and regulation. However, most multi-omics projects still include a limited number of molecular assays and...
Article
Full-text available
Background Tremendous opportunities for health research have been unlocked by the recent expansion of big data and artificial intelligence. However, this is an emergent area where recommendations for optimal use and implementation are needed. The objective of these European League Against Rheumatism (EULAR) points to consider is to guide the collec...
Article
Full-text available
Background: Due to limited access to brain tissue, the precise mechanisms underlying neuro-axonal dysfunction in neurological disorders such as multiple sclerosis (MS) are largely unknown. In that context, profiling DNA methylation, which is a stable and cell type-specific regulatory epigenetic mark of genome activity, offers a unique opportunity...
Article
Full-text available
The differentiation of self-renewing progenitor cells requires not only the regulation of lineage- and developmental stage-specific genes but also the coordinated adaptation of housekeeping functions from a metabolically active, proliferative state toward quiescence. How metabolic and cell-cycle states are coordinated with the regulation of cell ty...
Preprint
Full-text available
Background Profiling of mRNA expression is an important method to identify biomarkers but complicated by limited correlations between mRNA expression and protein abundance. We hypothesised that these correlations could be improved by mathematical models based on measuring splice variants and time delay in protein translation. Methods We characteri...
Article
Full-text available
Background: Multiple Sclerosis (MS) is a chronic inflammatory disease and a leading cause of progressive neurological disability among young adults. DNA methylation, which intersects genes and environment to control cellular functions on a molecular level, may provide insights into MS pathogenesis. Methods: We measured DNA methylation in CD4+ T...
Article
Full-text available
Regulatory T cells (Tregs) act as indispensable unit for maintaining peripheral immune tolerance mainly by regulating effector T cells. T cells resistant to suppression by Tregs pose therapeutic challenges in the treatment of autoimmune diseases, while augmenting susceptibility to suppression may be desirable for cancer therapy. To understand the c...
Preprint
GM-CSF produced by autoreactive CD4 positive T helper cells is involved in the pathogenesis of autoimmune diseases, such as Multiple Sclerosis. However, the molecular regulators that establish and maintain the features of GM-CSF positive CD4 T cells are unknown. In order to identify these regulators, we isolated human GM-CSF producing CD4 T cells f...
Article
Full-text available
Purpose: To investigate the cross-sectional and prospective associations between patterns of serum fat-soluble micronutrients and frailty in four European cohorts of older adults 65 years of age and older. Methods: Participants from the Three-City (Bordeaux, France), AMI (Gironde, France), TSHA (Toledo, Spain) and InCHIANTI (Tuscany, Italy) coho...
Article
Full-text available
Prenatal treatment with dexamethasone (DEX) reduces virilization in girls with congenital adrenal hyperplasia (CAH). It has potential short- and long-term risks and has been shown to affect cognitive functions. Here we investigate whether epigenetic modification of DNA during early developmental stages may be a key mediating mechanism by which pren...
Preprint
Full-text available
Networks are fundamental building blocks for representing data, and computations. Remarkable progress in learning in structurally defined (shallow or deep) networks has recently been achieved. Here we introduce evolutionary exploratory search and learning method of topologically flexible networks under the constraint of producing elementary computa...
Preprint
Full-text available
Rapid advances in single-cell assays have outpaced methods for analysis of those data types. Different single-cell assay show extensive variation in sensitivity and signal to noise levels. In particular, single-cell ATAC-seq generates extremely sparse and noisy datasets. Existing methods developed to analyze this data require cells amenable to pseu...