15 results on '"López-Domínguez R"'
Search Results
2. GeneCodis 4: Expanding the modular enrichment analysis to regulatory elements
- Author
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García-Moreno, A., primary, López-Domínguez, R., additional, Ramirez-Mena, A., additional, Pascual-Montano, A., additional, Aparicio-Puerta, E., additional, Hackenberg, M., additional, and Carmona-Saez, P., additional
- Published
- 2021
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3. Molecular subtypes explain lupus epigenomic heterogeneity unveiling new regulatory genetic risk variants.
- Author
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Castellini-Pérez O, Povedano E, Barturen G, Martínez-Bueno M, Iakovliev A, Kerick M, López-Domínguez R, Marañón C, Martín J, Ballestar E, Borghi MO, Qiu W, Zhu C, Shankara S, Spiliopoulou A, de Rinaldis E, Carnero-Montoro E, and Alarcón-Riquelme ME
- Abstract
The heterogeneity of systemic lupus erythematosus (SLE) can be explained by epigenetic alterations that disrupt transcriptional programs mediating environmental and genetic risk. This study evaluated the epigenetic contribution to SLE heterogeneity considering molecular and serological subtypes, genetics and transcriptional status, followed by drug target discovery. We performed a stratified epigenome-wide association studies of whole blood DNA methylation from 213 SLE patients and 221 controls. Methylation quantitative trait loci analyses, cytokine and transcription factor activity - epigenetic associations and methylation-expression correlations were conducted. New drug targets were searched for based on differentially methylated genes. In a stratified approach, a total of 974 differential methylation CpG sites with dependency on molecular subtypes and autoantibody profiles were found. Mediation analyses suggested that SLE-associated SNPs in the HLA region exert their risk through DNA methylation changes. Novel genetic variants regulating DNAm in disease or in specific molecular contexts were identified. The epigenetic landscapes showed strong association with transcription factor activity and cytokine levels, conditioned by the molecular context. Epigenetic signals were enriched in known and novel drug targets for SLE. This study reveals possible genetic drivers and consequences of epigenetic variability on SLE heterogeneity and disentangles the DNAm mediation role on SLE genetic risk and novel disease-specific meQTLs. Finally, novel targets for drug development were discovered., (© 2024. The Author(s).)
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- 2024
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4. Immune and molecular landscape behind non-response to Mycophenolate Mofetil and Azathioprine in lupus nephritis therapy.
- Author
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López-Domínguez R, Villatoro-García JA, Marañón C, Goldman D, Petri M, Carmona-Sáez P, Alarcón-Riquelme M, and Toro-Dominguez D
- Abstract
Lupus nephritis (LN) represents one of the most severe complications of systemic lupus erythematosus, leading to end-stage kidney disease in worst cases. Current first-line therapies for LN, including mycophenolate mofetil (MMF) and azathioprine (AZA), fail to induce long-term remission in 60-70% of the patients, evidencing the urgent need to delve into the molecular knowledge-gap behind the non-response to these therapies. A longitudinal cohort of treated LN patients including clinical, cellular and transcriptomic data, was analyzed. Gene-expression signatures behind non-response to different drugs were revealed by differential expression analysis. Drug-specific non-response mechanisms and cell proportion differences were identified. Blood cell subsets mediating non-response were described using single-cell RNASeq data. We show that AZA and MMF non-response implicates different cells and regulatory functions. Mechanistic models were used to suggest add-on therapies to improve their current performance. Our results provide new insights into the molecular mechanisms associated with treatment failures in LN.
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- 2024
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5. Response to the letter 'testing the effectiveness of MyPROSLE in classifying patients with lupus nephritis'.
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Toro-Domínguez D, Martorell-Marugán J, Martinez-Bueno M, López-Domínguez R, Carnero-Montoro E, Barturen G, Goldman D, Petri M, Carmona-Sáez P, and Alarcón-Riquelme ME
- Subjects
- Humans, Lupus Nephritis
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- 2023
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6. Exploring the interplay between climate, population immunity and SARS-CoV-2 transmission dynamics in Mediterranean countries.
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Villatoro-García JA, López-Domínguez R, Martorell-Marugán J, Luna JD, Lorente JA, and Carmona-Sáez P
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- Humans, Humidity, Temperature, Pandemics, SARS-CoV-2, COVID-19 epidemiology
- Abstract
The relationship between SARS-CoV-2 transmission and environmental factors has been analyzed in numerous studies since the outbreak of the pandemic, resulting in heterogeneous results and conclusions. This may be due to differences in methodology, considered variables, confounding factors, studied periods and/or lack of adequate data. Furthermore, previous works have reported that the lack of population immunity is the fundamental driver in transmission dynamics and can mask the potential impact of environmental variables. In this study, we aimed to investigate the association between climate variables and COVID-19 transmission considering the influence of population immunity. We analyzed two different periods characterized by the absence of vaccination (low population immunity) and a high degree of vaccination (high level of population immunity), respectively. Although this study has some limitations, such us the restriction to a specific climatic zone and the omission of other environmental factors, our results indicate that transmission of SARS-CoV-2 may increase independently of temperature and specific humidity in periods with low levels of population immunity while a negative association is found under conditions with higher levels of population immunity in the analyzed regions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Pedro Carmona-Saez reports financial support was provided by Government of Andalusia., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2023
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7. Scoring personalized molecular portraits identify Systemic Lupus Erythematosus subtypes and predict individualized drug responses, symptomatology and disease progression.
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Toro-Domínguez D, Martorell-Marugán J, Martinez-Bueno M, López-Domínguez R, Carnero-Montoro E, Barturen G, Goldman D, Petri M, Carmona-Sáez P, and Alarcón-Riquelme ME
- Subjects
- Disease Progression, Gene Regulatory Networks, Humans, Quality of Life, Autoimmune Diseases, Lupus Erythematosus, Systemic drug therapy, Lupus Erythematosus, Systemic genetics
- Abstract
Objectives: Systemic Lupus Erythematosus is a complex autoimmune disease that leads to significant worsening of quality of life and mortality. Flares appear unpredictably during the disease course and therapies used are often only partially effective. These challenges are mainly due to the molecular heterogeneity of the disease, and in this context, personalized medicine-based approaches offer major promise. With this work we intended to advance in that direction by developing MyPROSLE, an omic-based analytical workflow for measuring the molecular portrait of individual patients to support clinicians in their therapeutic decisions., Methods: Immunological gene-modules were used to represent the transcriptome of the patients. A dysregulation score for each gene-module was calculated at the patient level based on averaged z-scores. Almost 6100 Lupus and 750 healthy samples were used to analyze the association among dysregulation scores, clinical manifestations, prognosis, flare and remission events and response to Tabalumab. Machine learning-based classification models were built to predict around 100 different clinical parameters based on personalized dysregulation scores., Results: MyPROSLE allows to molecularly summarize patients in 206 gene-modules, clustered into nine main lupus signatures. The combination of these modules revealed highly differentiated pathological mechanisms. We found that the dysregulation of certain gene-modules is strongly associated with specific clinical manifestations, the occurrence of relapses or the presence of long-term remission and drug response. Therefore, MyPROSLE may be used to accurately predict these clinical outcomes., Conclusions: MyPROSLE (https://myprosle.genyo.es) allows molecular characterization of individual Lupus patients and it extracts key molecular information to support more precise therapeutic decisions., (© The Author(s) 2022. Published by Oxford University Press.)
- Published
- 2022
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8. Functional Enrichment Analysis of Regulatory Elements.
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Garcia-Moreno A, López-Domínguez R, Villatoro-García JA, Ramirez-Mena A, Aparicio-Puerta E, Hackenberg M, Pascual-Montano A, and Carmona-Saez P
- Abstract
Statistical methods for enrichment analysis are important tools to extract biological information from omics experiments. Although these methods have been widely used for the analysis of gene and protein lists, the development of high-throughput technologies for regulatory elements demands dedicated statistical and bioinformatics tools. Here, we present a set of enrichment analysis methods for regulatory elements, including CpG sites, miRNAs, and transcription factors. Statistical significance is determined via a power weighting function for target genes and tested by the Wallenius noncentral hypergeometric distribution model to avoid selection bias. These new methodologies have been applied to the analysis of a set of miRNAs associated with arrhythmia, showing the potential of this tool to extract biological information from a list of regulatory elements. These new methods are available in GeneCodis 4, a web tool able to perform singular and modular enrichment analysis that allows the integration of heterogeneous information.
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- 2022
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9. A comprehensive database for integrated analysis of omics data in autoimmune diseases.
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Martorell-Marugán J, López-Domínguez R, García-Moreno A, Toro-Domínguez D, Villatoro-García JA, Barturen G, Martín-Gómez A, Troule K, Gómez-López G, Al-Shahrour F, González-Rumayor V, Peña-Chilet M, Dopazo J, Sáez-Rodríguez J, Alarcón-Riquelme ME, and Carmona-Sáez P
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- Databases, Factual, Humans, Autoimmune Diseases epidemiology, Autoimmune Diseases genetics, Computational Biology
- Abstract
Background: Autoimmune diseases are heterogeneous pathologies with difficult diagnosis and few therapeutic options. In the last decade, several omics studies have provided significant insights into the molecular mechanisms of these diseases. Nevertheless, data from different cohorts and pathologies are stored independently in public repositories and a unified resource is imperative to assist researchers in this field., Results: Here, we present Autoimmune Diseases Explorer ( https://adex.genyo.es ), a database that integrates 82 curated transcriptomics and methylation studies covering 5609 samples for some of the most common autoimmune diseases. The database provides, in an easy-to-use environment, advanced data analysis and statistical methods for exploring omics datasets, including meta-analysis, differential expression or pathway analysis., Conclusions: This is the first omics database focused on autoimmune diseases. This resource incorporates homogeneously processed data to facilitate integrative analyses among studies.
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- 2021
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10. DatAC: A visual analytics platform to explore climate and air quality indicators associated with the COVID-19 pandemic in Spain.
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Martorell-Marugán J, Villatoro-García JA, García-Moreno A, López-Domínguez R, Requena F, Merelo JJ, Lacasaña M, de Dios Luna J, Díaz-Mochón JJ, Lorente JA, and Carmona-Sáez P
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- Betacoronavirus, COVID-19, Humans, Particulate Matter analysis, SARS-CoV-2, Spain epidemiology, Air Pollutants analysis, Air Pollution analysis, Coronavirus, Coronavirus Infections, Pandemics, Pneumonia, Viral
- Abstract
The coronavirus disease 2019 (COVID-19) pandemic has caused an unprecedented global health crisis, with several countries imposing lockdowns to control the coronavirus spread. Important research efforts are focused on evaluating the association of environmental factors with the survival and spread of the virus and different works have been published, with contradictory results in some cases. Data with spatial and temporal information is a key factor to get reliable results and, although there are some data repositories for monitoring the disease both globally and locally, an application that integrates and aggregates data from meteorological and air quality variables with COVID-19 information has not been described so far to the best of our knowledge. Here, we present DatAC (Data Against COVID-19), a data fusion project with an interactive web frontend that integrates COVID-19 and environmental data in Spain. DatAC is provided with powerful data analysis and statistical capabilities that allow users to explore and analyze individual trends and associations among the provided data. Using the application, we have evaluated the impact of the Spanish lockdown on the air quality, observing that NO
2 , CO, PM2.5 , PM10 and SO2 levels decreased drastically in the entire territory, while O3 levels increased. We observed similar trends in urban and rural areas, although the impact has been more important in the former. Moreover, the application allowed us to analyze correlations among climate factors, such as ambient temperature, and the incidence of COVID-19 in Spain. Our results indicate that temperature is not the driving factor and without effective control actions, outbreaks will appear and warm weather will not substantially limit the growth of the pandemic. DatAC is available at https://covid19.genyo.es., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)- Published
- 2021
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11. Analysis of Sport Supplement Consumption and Body Composition in Spanish Elite Rowers.
- Author
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Domínguez R, López-Domínguez R, López-Samanes Á, Gené P, González-Jurado JA, and Sánchez-Oliver AJ
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- Adiposity, Anthropometry, Athletes, Body Height, Body Weight, Caffeine administration & dosage, Electric Impedance, Energy Intake, Female, Humans, Iron, Dietary administration & dosage, Male, Spain, Vitamins administration & dosage, Young Adult, beta-Alanine administration & dosage, Body Composition, Dietary Supplements, Sports Nutritional Physiological Phenomena, Water Sports
- Abstract
The aim of this study was to analyze the anthropometric characteristics and sport supplement (SS) consumption patterns of heavyweight and lightweight international rowers. Methods: The 13 heavyweights (11 males) and seven lightweights (five males) of the Spanish National Rowing Team were recruited for the study. Body composition was measured by bio-impedance analysis, and the questionnaire used in this investigation was previously validated to assess SS consumption. According to anthropometrics parameters, it was reported that male heavyweight rowers were heavier ( p < 0.001) and taller ( p < 0.001), but no statistical differences were reported for % body fat ( p = 0.104) or % lean body mass ( p = 0.161). All rowers reported consumption of at least one SS. Based on the Australian Institute of Sport's classification, higher medical supplement consumption was observed when comparing heavyweight rowers to lightweight rowers (2.5 ± 1.1 vs. 1.7 ± 0.5, p = 0.040). There were no differences in the totals of group A (strong scientific evidence for sports scenarios, p = 0.069), group B (emerging scientific support, deserving of further research, p = 0.776), or group C (scientific evidence not supportive of benefit and/or security amongst athletes, p = 0.484). The six most consumed SSs were iron (85%), caffeine (85%), β-alanine (85%), energy bars (85%), vitamin supplements (80%), and isotonic drinks (80%), with no statistical differences between heavyweight and lightweight rowers ( p > 0.05). These results suggest that the absence of differences in body composition (expressed as a percentage) do not represent anthropometric disadvantages for heavyweight rowers. In addition, SS consumption was similar between rowers, reporting only higher medical supplement consumption in heavyweight rowers.
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- 2020
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12. Extracellular Protease ADAMTS1 Is Required at Early Stages of Human Uveal Melanoma Development by Inducing Stemness and Endothelial-Like Features on Tumor Cells.
- Author
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Peris-Torres C, Plaza-Calonge MDC, López-Domínguez R, Domínguez-García S, Barrientos-Durán A, Carmona-Sáez P, and Rodríguez-Manzaneque JC
- Abstract
Extracellular matrix remodeling within the tumor microenvironment has been recognized as a relevant dynamic framework during tumor growth. However, research on proteases that trigger this remodeling keeps revealing a wide range of actions including both pro- and anti-tumorigenic. The extracellular protease ADAMTS1 exemplifies this dual role. In this work, we first confirmed a positive correlation of ADAMTS1 with endothelial-like phenotype of human melanoma cells together with the finding of associated signatures, including key genes such as endothelial CDH5 . Using a CRISPR-Cas9 approach, we observed that the inhibition of ADAMTS1 in an aggressive uveal melanoma model compromised its endothelial-like properties, and more importantly, caused a robust blockade on the progression of tumor xenografts. Although vasculature emerged affected in ADAMTS1-deficient tumors, the most relevant action implied the downregulation of endothelial CDH5 in tumor cells, in association with stemness markers. Indeed, melanoma sphere assays also revealed a deficient commitment to form spheres in the absence of ADAMTS1, directly correlating with stemness markers and, remarkably, also with CDH5. Finally, taking advantage of advanced bioinformatics tools and available public data of uveal melanomas, we disclosed new prognosis factors, including endothelial elements and ADAMTS proteases. Our findings support the key role of ADAMTS proteases for uveal melanoma development since earlier stages, modulating the complex crosstalk between extracellular matrix and the induction of stemness and endothelial-like features. To our knowledge, this is the first report that supports the development of therapeutic targets on the extracellular matrix to overcome uveal melanoma., Competing Interests: The authors declare no conflict of interest.
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- 2020
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13. ImaGEO: integrative gene expression meta-analysis from GEO database.
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Toro-Domínguez D, Martorell-Marugán J, López-Domínguez R, García-Moreno A, González-Rumayor V, Alarcón-Riquelme ME, and Carmona-Sáez P
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- Biomarkers, Databases, Factual, Gene Expression, Reproducibility of Results, Gene Expression Profiling
- Abstract
Summary: The Gene Expression Omnibus (GEO) database provides an invaluable resource of publicly available gene expression data that can be integrated and analyzed to derive new hypothesis and knowledge. In this context, gene expression meta-analysis (geMAs) is increasingly used in several fields to improve study reproducibility and discovering robust biomarkers. Nevertheless, integrating data is not straightforward without bioinformatics expertise. Here, we present ImaGEO, a web tool for geMAs that implements a complete and comprehensive meta-analysis workflow starting from GEO dataset identifiers. The application integrates GEO datasets, applies different meta-analysis techniques and provides functional analysis results in an easy-to-use environment. ImaGEO is a powerful and useful resource that allows researchers to integrate and perform meta-analysis of GEO datasets to lead robust findings for biomarker discovery studies., Availability and Implementation: ImaGEO is accessible at http://bioinfo.genyo.es/imageo/., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2019
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14. [Bacteremia due to Campylobacter jejuni: report of two cases].
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Cesteros RI, Menasalvas AI, Guerrero C, López-Domínguez R, Miranda A, and Segovia M
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- Adult, Aged, Humans, Male, Bacteremia microbiology, Campylobacter Infections complications, Campylobacter jejuni
- Published
- 2001
15. [Activity of new quinolones against clinical isolates of Corynebacterium species].
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Yagüe Guirao G, Martínez-Toldos MC, Mora Peris B, López Domínguez R, Romero Otero M, Muñoz Bellido JL, and Segovia Hernández M
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- Anti-Infective Agents therapeutic use, Corynebacterium Infections microbiology, Drug Resistance, Microbial, Fluoroquinolones, Humans, Microbial Sensitivity Tests, Anti-Infective Agents pharmacology, Corynebacterium drug effects
- Abstract
The activity of six quinolones (ciprofloxacin, levofloxacin, trovafloxacin, moxifloxacin, clinafloxacin and grepafloxacin) against 86 clinical isolates of Corynebacterium spp. obtained from different clinical sources was studied. Of these, 30 isolates were identified as C. jeikeium, 30 as C. urealyticum and 26 as C. amycolatum. C. amycolatum was the most resistant species, with 85.5% of the strains analyzed resistant to all the quinolones studied. Clinafloxacin showed the best activity against these species with a concentration range between <0.01 and 8 mg/l, and MIC50 and MIC90 64 and 32 times lower, respectively, than the MICs of ciprofloxacin. The majority of the isolates (90%) of C. jeikeium and C. urealyticum were susceptible to all the quinolones studied. Only 9.9% of the C. jeikeium strains and 13.2% of the C. urealyticum strains were resistant to ciprofloxacin, which showed the lowest activity of the antimicrobial agents evaluated. Clinafloxacin, grepafloxacin and moxifloxacin were the most active quinolones against these two multiresistant species.
- Published
- 2000
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