The DisGeNET cytoscape app: Exploring and visualizing disease genomics data

Computational and Structural Biotechnology Journal, Год журнала: 2021, Номер 19, С. 2960 - 2967

Опубликована: Янв. 1, 2021

Thanks to the unbiased exploration of genomic variants at large scale, hundreds thousands disease-associated loci have been uncovered. In parallel, network-based approaches proven be essential understand molecular mechanisms underlying human diseases. The use these has boosted by abundance information about disease associated genes and variants, high quality interactomics data, emergence new types omics data. DisGeNET Cytoscape App combines capabilities with those DisGeNET, a knowledge platform based on comprehensive catalogue variants. contains functions query, analyze, visualize different network representations gene-disease variant-disease associations available in DisGeNET. It supports wide variety applications through its query filter functionalities, including annotation foreign networks generated other apps or uploaded user. release designed support 3.x incorporates novel distinctive features such as visualization analysis networks, enrichment for analytic Automation. Moreover, an API access core functionalities via REST protocol fostering development reproducible scalable workflows

Язык: Английский

---

A single-cell atlas of chromatin accessibility in the human genome

Cell, Год журнала: 2021, Номер 184(24), С. 5985 - 6001.e19

Опубликована: Ноя. 1, 2021

Current catalogs of regulatory sequences in the human genome are still incomplete and lack cell type resolution. To profile activity gene elements diverse types tissues body, we applied single-cell chromatin accessibility assays to 30 adult tissue from multiple donors. We integrated these datasets with previous data 15 fetal reveal status open for ∼1.2 million candidate cis-regulatory (cCREs) 222 distinct comprised >1.3 nuclei. used maps delineate cell-type-specificity cCREs systematically interpret noncoding variants associated complex traits diseases. This rich resource provides a foundation analysis programs across tissues, life stages, organ systems.

Язык: Английский

---

Asthma

The Lancet, Год журнала: 2023, Номер 401(10379), С. 858 - 873

Опубликована: Янв. 20, 2023

Язык: Английский

---

Advances in asthma: New understandings of asthma’s natural history, risk factors, underlying mechanisms, and clinical management

Journal of Allergy and Clinical Immunology, Год журнала: 2021, Номер 148(6), С. 1430 - 1441

Опубликована: Окт. 14, 2021

Язык: Английский

---

Genome-wide analysis highlights contribution of immune system pathways to the genetic architecture of asthma

Nature Communications, Год журнала: 2020, Номер 11(1)

Опубликована: Апрель 15, 2020

Asthma is a chronic and genetically complex respiratory disease that affects over 300 million people worldwide. Here, we report genome-wide analysis for asthma using data from the UK Biobank Trans-National Genetic Consortium. We identify 66 previously unknown loci demonstrate susceptibility alleles in these regions are, either individually or as function of cumulative genetic burden, associated with risk to greater extent men than women. Bioinformatics analyses prioritize candidate causal genes at 52 loci, including CD52, asthma-associated variants are enriched open chromatin immune cells. Lastly, show murine anti-CD52 antibody mimics cell-depleting effects clinically used human reduces allergen-induced airway hyperreactivity mice. These results further elucidate architecture provide important insight into immunological sex-specific relevance variants.

Язык: Английский

---

Role of viruses in asthma

Seminars in Immunopathology, Год журнала: 2020, Номер 42(1), С. 61 - 74

Опубликована: Янв. 27, 2020

Respiratory viral infections are the most important triggers of asthma exacerbations. Rhinovirus (RV), common cold virus, is clearly prevalent pathogen constantly circulating in community. This virus also stands out from other factors due to its large diversity (about 170 genotypes), very effective replication, a tendency create Th2-biased inflammatory environment and association with specific risk genes people predisposed development (CDHR3). Decreased interferon responses, disrupted airway epithelial barrier, environmental exposures (including biased microbiome), nutritional deficiencies (low vitamin D fish oil) increase RV infections. It intensively debated whether illnesses actually cause asthma. syncytial (RSV) leading causative agent bronchiolitis, whereas starts dominate after 1 year age. Breathing difficulty induced by either these viruses associated later asthma, but higher for those who suffer severe RV-induced wheezing. The has unique mechanisms, general, factor atopic RSV more likely non-atopic Treatments that inhibit inflammation (corticosteroids, omalizumab) effectively decrease wheezing anti-RSV monoclonal antibody, palivizumab, decreases illness subsequent recurrent wheeze. A better understanding personal mechanisms crucial developing new strategies prevention treatment

Язык: Английский

---

Functions and regulation of T cell-derived interleukin-10

Seminars in Immunology, Год журнала: 2019, Номер 44, С. 101344 - 101344

Опубликована: Авг. 1, 2019

Язык: Английский

---

Genetics and Epigenetics in Asthma

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(5), С. 2412 - 2412

Опубликована: Фев. 27, 2021

Asthma is one of the most common respiratory disease that affects both children and adults worldwide, with diverse phenotypes underlying pathogenetic mechanisms poorly understood. As technology in genome sequencing progressed, scientific efforts were made to explain predict asthma’s complexity heterogeneity, genome-wide association studies (GWAS) quickly became preferred study method. Several gene markers loci associated asthma susceptibility, atopic childhood-onset identified during last few decades. Markers near ORMDL3/GSDMB genes asthma, interleukin (IL)33 IL1RL1 SNPs Thymic Stromal Lymphopoietin (TSLP) was as protective against risk TH2-asthma. The latest advances identifying decoding susceptibility are focused on epigenetics, heritable characteristics affect expression without altering DNA sequence, methylation being described mechanism. Other less studied epigenetic include histone modifications alterations miR expression. Recent findings suggest pattern tissue cell-specific. attempt describe different types cells tissues asthmatic patients regulate airway remodeling, phagocytosis, other lung functions asthma. In this review, we briefly present advancements field genetics mainly epigenetics concerning susceptibility.

Язык: Английский

---

Cutaneous barrier dysfunction in allergic diseases

Journal of Allergy and Clinical Immunology, Год журнала: 2020, Номер 145(6), С. 1485 - 1497

Опубликована: Июнь 1, 2020

Язык: Английский

---

Cellular and molecular mechanisms of allergic asthma

Molecular Aspects of Medicine, Год журнала: 2021, Номер 85, С. 100995 - 100995

Опубликована: Авг. 5, 2021

Asthma is a chronic disease of the airways, which affects more than 350 million people worldwide. It most common in children, affecting at least 30 children and young adults Europe. complex, partially heritable with marked heterogeneity. Its development influenced both by genetic environmental factors. The common, as well characterized subtype asthma allergic eosinophilic asthma, type 2 airway inflammation. prevalence has substantially increased industrialized countries during last 60 years. mechanisms underpinning this phenomenon are incompletely understood, however exposure to various pollutants probably plays role. Disease inception thought be enabled disadvantageous shift balance between protective harmful lifestyle factors, including commensal microbes versus infection pathogens, collectively leading epithelial cell damage disrupted barrier integrity. Epithelial cell-derived cytokines one main drivers immune response against innocuous allergens, ultimately infiltration lung tissue T helper (TH2) cells, innate lymphoid cells (ILC2s), M2 macrophages eosinophils. This review outlines responsible for orchestration inflammation summarizes novel findings, but not limited dysregulated integrity, alarmin release stimulation.

Язык: Английский

---