Search

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Epigenetic changes can drive drug resistance in cancer. Here, the authors show that in BET inhibitor resistant leukaemia cells, genome-wide enhancer remodelling drives therapeutic resistance and targeting enhancer plasticity may overcome this resistance.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Monitoring COVID-19 vaccine uptake in those at risk of severe disease, such as people with mental illness, is important. Here, the authors use cohort and/or health registry data from five countries in northern Europe and investigate vaccine uptake by mental illness and treatment status.

A comprehensive multi-omics reference atlas of prenatal human skin shows that innate immune cells crosstalk with non-immune cells to perform pivotal roles in skin morphogenesis, including the formation of hair follicles.

A multiomic atlas of human embryonic joint and cranium development enables detailed analysis of bone and cartilage maturation.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

The maintenance of T resident memory (T_RM) cells within pulmonary tissues is incompletely understood. Here the authors show that antigen presentation by lung epithelial cells maintains function and phenotype of pulmonary T_RM cells within specific locational niches.

Biomarkers to indicate potential response to biologic therapeutics are needed for patients with psoriasis. Here the authors show that phosphorylation of NFκBp65 in cDC2 before therapy is an indication of non-response to the anti-TNF therapy adalimumab in patients with psoriasis.

K. Lenhard Rudolph and colleagues report that conditional p53 deletion in the intestinal epithelium of aging mice impaired the depletion of chromosomal-instable stem cells and shortened the lifespan of telomere-dysfunctional mice without inducing tumor formation.

Analyses of three high-quality genomes of Anthoceros hornworts place hornworts as a sister clade to the lineage including liverworts and mosses, and provide insights into the unique biological features of hornworts.

Transcriptomic analysis may provide information about the differentiation state and cell of origin of a cancer. Here, the authors assess mRNA signals in 1300 childhood and adult renal tumors and report a fetal origin of childhood tumors and no dedifferentiation of adult tumors.

DNA supercoiling strongly affects its metabolism. By electron cryo-tomography, biochemical assays and molecular dynamics simulations, here the authors show that supercoiled DNA minicircles adopt unique and wide distributions of three-dimensional conformations, many with disrupted base pairs.

An extensive phylogenomics study based on hundreds of genomes and transcriptomes provides a new interpretation of the evolution of different types of symbiotic associations in land plants, and reveals a conserved ancestral symbiosis pathway.

The response to infectious and inflammatory challenges differs among people but the reasons for this are poorly understood. Here the authors explore the impact of variables such as age, sex, and the capacity for controlling inflammation and maintaining immunocompetence, linking this capacity to favourable health outcomes and lifespan.

Atopic dermatitis (AD) and psoriasis (PSO) are associated with dysbiosis. Here, by analyses of skin microbiome and host transcriptome of AD and PSO patients, the authors find distinct microbial and disease-related gene transcriptomic signatures that differentiate both diseases.

Acne vulgarisis a common, inflammatory skin disorder. Here the authors carry out a genome-wide association study and identify three genetic variants that associate with an increased risk of developing acne, which together suggest a mechanistic role for the TGFβ cell signalling pathway in acne development and progression.

With a comprehensive analysis of sequencing data, DNA copy number, gene expression and DNA methylation in a large number of human glioblastomas, The Cancer Genome Atlas project initiative provides a broad overview of the genes and pathways that are altered in this cancer type.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

Phenotypic variation and diseases are influenced by factors such as genetic variants and gene expression. Here, Barbeira et al. develop S-PrediXcan to compute PrediXcan results using summary data, and investigate the effects of gene expression variation on human phenotypes in 44 GTEx tissues and >100 phenotypes.

Multiple transcriptome approaches, including single-cell sequencing, demonstrate that escape from X chromosome inactivation is widespread and occasionally variable between cells, chromosomes, and tissues, resulting in sex-biased expression of at least 60 genes and potentially contributing to sex-specific differences in health and disease.

Patients’ selection is particularly important in cancer treatment. Here the authors present a proof-of-principle methodology that could be potentially important in assisting therapeutic decisions in the treatment of breast cancer patients.

Using the GTEx data and others, a comprehensive analysis of adenosine-to-inosine RNA editing in mammals is presented; targets of the various ADAR enzymes are identified, as are several potential regulators of editing, such as AIMP2.

The authors show that rare genetic variants contribute to large gene expression changes across diverse human tissues and provide an integrative method for interpretation of rare variants in individual genomes.

Around 10% of high-grade serous ovarian carcinomas (HGSOC) harbor BRCA1 promoter methylation, but it is uncertain how it predicts response to PARP inhibition. Here, the authors show that homozygous BRCA1 methylation predicts response to rucaparib while heterozygous methylation of BRCA1 predicts resistance in HGSOC.

New World hantaviruses—which cause a severe human respiratory disease—use surface glycoproteins to bind to the human protocadherin-1 protein and enter endothelial cells in vitro; depleting protocadherin-1 in Syrian golden hamsters largely protects against disease.