Diseases

A time-resolved high-resolution map of human cardiac remodelling after myocardial infarction, integrating single-cell transcriptomic, chromatin accessibility and spatial transcriptomic data, provides a valuable resource for the field.

Copy number variations inferred from spatial transcriptomics data in benign and malignant tissue reveal clonal architecture at the organ-wide level.

Truncation of exon 18 of FGFR2 (FGFR2^ΔE18) is a potent driver mutation in mice and humans, and FGFR-targeted therapy should be considered for patients with cancer expressing stable FGFR2^ΔE18 variants.

Inhibiting the asialoglycoprotein receptor ASGR1 increases cholesterol excretion to the bile and then faeces, providing a unique way to lower cholesterol, and therefore providing a safe and effective way to treat cardiovascular disease.

cis-RNA editing quantitative trait loci, which are associated with immunogenic double-stranded RNAs, underlie genome-wide association study variants in common autoimmune and inflammatory diseases.

Deep whole-genome sequencing of serial blood samples and matched metastatic tissue reveals that circulating tumour DNA profiling enables detailed study of treatment-driven subclone dynamics, epigenomics and genome-wide somatic evolution in metastatic human cancers.

In addition to its role in suppressing MDA5 and PKR activation, ADAR1 is a negative regulator of ZPB1-mediated apoptosis and necroptosis, providing insights into the pathology of Aicardi–Goutières syndrome.

Oocytes prevent the production of reactive oxygen species by remodelling the mitochondrial electron transport chain through elimination of complex I, a strategy that enables their long-term viability.

A genetic lineage-tracing system in human colorectal organoids identifies a population of dormant cancer cells that persists during chemotherapy and enables cancer regrowth, and the cell-adhesion molecule COL17A1 has a key role in the process of breaking dormancy.

Single-nuclear transcriptomic and proteomic analyses identify molecular characteristics shared by multiple classes of congenital heart disease, including phenotypes associated with insulin resistance.

The lineage transcription factor PAX8 is shown to play a pivotal part in determining cancer risk in clear cell renal cell carcinoma, providing insights into how genetic mutations lead to specific types of cancer.

A long-term study of 385 human donors reports that driver gene mutations and age determine the lifelong dynamics of clonal haematopoiesis

A computational system termed MetaWIBELE (workflow to identify novel bioactive elements in the microbiome) is used to identify microbial gene products that are potentially bioactive and have a functional role in the pathogenesis of inflammatory bowel disease.

A multiomics resource characterizing human mitochondrial proteins enables identification of biological functions and supports genetic diagnosis of mitochondrial pathologies.

Characterization of Gibbin, encoded by AHDC1, offers insights into the epidermal and mesodermal patterning phenotypes seen in Xia–Gibbs and related syndromes in humans, which derive from abnormal mesoderm maturation as a result of gene-specific DNA methylation decisions.

A study quantifying the neutralization of severe acute respiratory syndrome coronavirus 2 variants in individuals infected with Omicron/BA.1 shows that vaccinated individuals previously infected with Omicron have enhanced protection against reinfection with current variants, \including Omicron/BA.2, while Omicron/BA.1 infected unvaccinated individuals have limited protection.

The peripheral nervous system uses neuroimmune cardiovascular interfaces to assemble a structural artery–brain circuit, and therapeutic intervention in the artery–brain circuit attenuates atherosclerosis.

Whole-exome sequencing identifies ten risk genes for schizophrenia implicated by rare protein-coding variants, a subset of which overlap with risk genes in other neurodevelopmental disorders.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

The SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme provides a real-time risk assessment of SARS-CoV-2 variants with the potential to affect transmission, virulence and resistance to infection- and vaccine-induced immunity.

Genetically diverse Candida albicans strains in patients with inflammatory bowel disease secrete a toxin and aggravate IL-1β-dependent intestinal inflammation.

Detailed reconstruction using enhanced focused ion beam scanning electron microscopy imaging and deep-learning-based automated segmentation demonstrates that hepatocyte subcellular organelle architecture regulates metabolism.

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.

A meta-analysis combining whole-exome sequencing data from UK Biobank participants and imputed genotypes from FinnGen participants enables identification of genetic associations with human disease in the rare and low-frequency allelic spectrum

In monozygotic twins discordant for multiple sclerosis, the influence of genetic predisposition and environmental factors is determined using matched-pair analyses.

T cell responses to spike protein from the SARS-CoV-2 Omicron variant (B.1.1.529) are broadly similar to the responses to ancestral, Beta (B.1.351) and Delta (B.1.617.2) spike protein in vaccinated, infected and unvaccinated individuals.

The COVID Human Genetic Effort examines the molecular, cellular and immunological determinants of the various SARS-CoV-2-related disease manifestations by searching for causal errors of immunity.

Whole-genome sequencing of 1,013 clonal haematopoietic colonies from myeloproliferative neoplasms of 12 individuals reveals haematopoietic phylogenies and indicates that driver mutations are acquired sequentially, starting early in life.

More than one-third of wild deer tested in northeast Ohio showed evidence of SARS-CoV-2 infection of human origin.

The Alpha variant of SARS-CoV-2 outcompetes progenitor SARS-CoV-2 in upper respiratory tract replication competition in vivo.

Interim analysis of a phase III clinical trial of HER2-positive gastric adenocarinoma shows pembrolizumab plus trastuzumab and chemotherapy improves response rates compared with trastuzumab and chemotherapy alone.

A strong association has been found between three regions of the Plasmodium falciparum genome and sickle haemoglobin in children with severe malaria, suggesting parasites have adapted to overcome natural host immunity.

The potential origins and global spread of SARS-CoV-2, the emergence of SARS-CoV-2 variants of concern and the importance of genomic surveillance for the control of the COVID-19 pandemic are discussed.

A study of mice exposed to cigarette smoke suggests that smoking-cessation-induced weight gain is associated with a dysbiotic state that is driven by smoking-related metabolites.

An analysis of three surveys of COVID-19 vaccine behaviour shows that larger surveys overconfidently overestimated vaccine uptake, a demonstration of how larger sample sizes can paradoxically lead to less accurate estimates.

An analysis of 2,173 individuals from the MetaCardis cohort quantifies the individual and combinatorial effects of a range of drugs on host health, metabolome and gut microbiome in cardiometabolic disease.

Using cryogenic electron microscopy, the structure of the human SGLT2–MAP17 complex captured in the empagliflozin-bound state reveals the inhibitory mechanism of these anti-diabetic drugs.

A population of β-cell-specific autoimmune stem-like CD8 T cells initiates and sustains β-cell destruction and disease in a mouse model of type 1 diabetes.

Whole-transcriptome sequencing of a subset of 75 non-small-cell lung cancer specimens in a multi-institutional genome screening study identified a fusion of the CLIP1 and LTK genes with transformational potential due to constitutive LTK kinase activity.

A phase I open-label trial evaluating the immunogencity, reactogenicity and safety of a peptide-based SARS-CoV-2 vaccine candidate to induce SARS-CoV-2-specific T cell responses.

Dysfunction of mitochondrial complex I in mice is sufficient to cause progressive parkinsonism in which the loss of nigral dopamine release critically contributes to motor dysfunction.

Cryo-EM structure of Nf1 protein is reported, revealing closed and open conformations that regulate interaction with Ras oncogene, setting the stage for understanding the mechanistic action of Nf1 and how disease mutations lead to dysfunction.

An observational study of more than 13,000 healthcare workers shows that a prime–boost vaccine regimen of AstraZeneca ChAdOx1-S-nCoV-19 with Pfizer BNT162b2 provides enhanced protection against SARS-CoV-2 infection compared with two doses of BNT162b2.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Whole-genome sequencing analysis of somatic mutations in liver samples from patients with chronic liver disease identifies driver mutations in metabolism-related genes such as FOXO1, and shows that these variants frequently exhibit convergent evolution.

Monitoring of western chimpanzee populations in Guinea-Bissau and Côte d’Ivoire reveals the presence of rare and different genotypes of Mycobacterium leprae, suggesting greater circulation in wild animals than previously thought.