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Sökning: WFRF:(Navarro José Fernández)

  • Resultat 1-10 av 35
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1.
  • Cruz, Raquel, et al. (författare)
  • Novel genes and sex differences in COVID-19 severity
  • 2022
  • Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
  • Tidskriftsartikel (refereegranskat)abstract
    • Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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2.
  • Kehoe, Laura, et al. (författare)
  • Make EU trade with Brazil sustainable
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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3.
  • Hudson, Lawrence N, et al. (författare)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Tidskriftsartikel (refereegranskat)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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  • 2017
  • swepub:Mat__t
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6.
  • Andersson, Alma, et al. (författare)
  • Single-cell and spatial transcriptomics enables probabilistic inference of cell type topography
  • 2020
  • Ingår i: Communications Biology. - : Nature Research. - 2399-3642. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The field of spatial transcriptomics is rapidly expanding, and with it the repertoire of available technologies. However, several of the transcriptome-wide spatial assays do not operate on a single cell level, but rather produce data comprised of contributions from a – potentially heterogeneous – mixture of cells. Still, these techniques are attractive to use when examining complex tissue specimens with diverse cell populations, where complete expression profiles are required to properly capture their richness. Motivated by an interest to put gene expression into context and delineate the spatial arrangement of cell types within a tissue, we here present a model-based probabilistic method that uses single cell data to deconvolve the cell mixtures in spatial data. To illustrate the capacity of our method, we use data from different experimental platforms and spatially map cell types from the mouse brain and developmental heart, which arrange as expected.
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7.
  • Arad-Cohen, Nira, et al. (författare)
  • Supportive care in pediatric acute myeloid leukemia:Expert-based recommendations of the NOPHO-DB-SHIP consortium
  • 2022
  • Ingår i: Expert Review of Anticancer Therapy. - : Taylor & Francis Group. - 1473-7140 .- 1744-8328. ; 22:11, s. 1183-1196
  • Forskningsöversikt (refereegranskat)abstract
    • Introduction Pediatric acute myeloid leukemia (AML) is the second most common type of pediatric leukemia. Patients with AML are at high risk for several complications such as infections, typhlitis, and acute and long-term cardiotoxicity. Despite this knowledge, there are no definite supportive care guidelines as to what the best approach is to manage or prevent these complications. Area covered The NOPHO-DB-SHIP (Nordic-Dutch-Belgian-Spain-Hong-Kong-Israel-Portugal) consortium, in preparation for a new trial in pediatric AML patients, had dedicated meetings for supportive care. In this review, the authors discuss the available data and outline recommendations for the management of children and adolescents with AML with an emphasis on hyperleukocytosis, tumor lysis syndrome, coagulation abnormalities and bleeding, infection, typhlitis, malnutrition, cardiotoxicity, and fertility preservation. Expert opinion Improved supportive care has significantly contributed to increased cure rates. Recommendations on supportive care are an essential part of treatment for this highly susceptible population and will further improve their outcome.
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8.
  • Asp, Michaela, et al. (författare)
  • Spatial detection of fetal marker genes expressed at low level in adult human heart tissue
  • 2017
  • Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Heart failure is a major health problem linked to poor quality of life and high mortality rates. Hence, novel biomarkers, such as fetal marker genes with low expression levels, could potentially differentiate disease states in order to improve therapy. In many studies on heart failure, cardiac biopsies have been analyzed as uniform pieces of tissue with bulk techniques, but this homogenization approach can mask medically relevant phenotypes occurring only in isolated parts of the tissue. This study examines such spatial variations within and between regions of cardiac biopsies. In contrast to standard RNA sequencing, this approach provides a spatially resolved transcriptome- and tissue-wide perspective of the adult human heart, and enables detection of fetal marker genes expressed by minor subpopulations of cells within the tissue. Analysis of patients with heart failure, with preserved ejection fraction, demonstrated spatially divergent expression of fetal genes in cardiac biopsies.
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9.
  • Chen, Wei-Ting, et al. (författare)
  • Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease
  • 2020
  • Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 182:4, s. 976-
  • Tidskriftsartikel (refereegranskat)abstract
    • Although complex inflammatory-like alterations are observed around the amyloid plaques of Alzheimer's disease (AD), little is known about the molecular changes and cellular interactions that characterize this response, We investigate here, in an AD mouse model, the transcriptional changes occurring in tissue domains in a 100-mu m diameter around amyloid plaques using spatial transcriptomics. We demonstrate early alterations in a gene co-expression network enriched for myelin and oligodendrocyte genes (OLIGs), whereas a multicellular gene co-expression network of plaque-induced genes (PIGs) involving the complement system, oxidative stress, lysosomes, and inflammation is prominent in the later phase of the disease. We confirm the majority of the observed alterations at the cellular level using in situ sequencing on mouse and human brain sections. Genome-wide spatial transcriptomics analysis provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases.
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10.
  • Fernandez Navarro, Jose, 1982- (författare)
  • Computational methods for analysis and visualization of spatially resolved transcriptomes
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Characterizing the expression level of genes (transcriptome) in cells and tis- sues is essential for understanding the biological processes of multicellular or- ganisms. RNA sequencing (RNA-seq) has gained traction in the last decade as a powerful tool that provides an accurate quantitative representation of the transcriptome in tissues. RNA-seq methods are, however, limited by the fact that they provide an average representation of the transcriptome across the tissue. Single cell RNA sequencing (scRNA-seq) provides quantitative gene expression levels of individual cells. This enables the molecular characteri- zation of cell types in health, disease and developmental tissues. However, scRNA-seq lacks the spatial context needed to understand how cells interact and their microenvironment. Current methods that provide spatially resolved gene expression levels are limited by a low throughput and the fact that the target genes must be known in advance.Spatial Transcriptomics (ST) is a novel method that combines high-resolution imaging with high-throughput sequencing. ST provides spatially resolved gene expression levels in tissue sections. The first part of the work presented in this thesis (Papers I, II, III and IV) revolves around the ST method and the development of the computational tools required to process, analyse and visualize ST data.Furthermore, the ST method was utilized to construct a three-dimensional (3D) molecular atlas of the adult mouse brain using 75 consecutive coronal sections (Paper V). We show that the molecular clusters obtained by unsu- pervised clustering of the atlas highly correlates with the Allen Brain Atlas. The molecular clusters provide new insights in the organization of regions like the hippocampus or the amygdala. We show that the molecular atlas can be used to spatially map single cells (scRNA-seq) onto the clusters and that only a handful of genes is required to define the brain regions at a molecular level.Finally, the hippocampus and the olfactory bulb of transgenic mice mim- icking the Alzheimer’s disease (AD) were spatially characterized using the ST method (Paper VI). Dierential expression analysis revealed genes central in areas highly cited as important in AD including lipid metabolism, cellular bioenergetics, mitochondrial function, stress response and neurotransmission.
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