Search

The changing cellular, transcriptional, and genomic landscape of human lung aging can be characterized using single-cell RNA sequencing. Here, the authors show that lung aging is cell-type dyssynchronous, with alveolar epithelial and endothelial cells exhibiting the greatest changes in gene expression, transcriptional entropy, and a high level of somatic mutations.

In a phase 2 trial evaluating healthy donor fecal microbial transplantation plus either anti-PD-1 in patients with non-small cell lung cancer or anti-PD-1 and anti-CTLA-4 in patients with melanoma, encouraging efficacy was seen in both cohorts, with responses linked to significantly greater loss of baseline bacterial species.

Psoriasis is a difficult to treat chronic skin condition that could be limiting to quality of life. Here, authors present results of the phase 2 randomized clinical trial KNOCKOUT (NCT05283135) in which they treated patients with moderate-to-severe plaque psoriasis with higher-than-approved doses of risankizumab, an interleukin-23 inhibitor, to show high skin clearance rates and decreased tissue resident memory T cell numbers in the lesional skin.

This study uses single-cell DNA sequencing to analyze genomic evolution in pancreatic cancer using a cohort of multiregionally and longitudinally sampled patients’ tissues across various clinical contexts.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

Schuermans et al. discovered that genetic predisposition to thromboembolism is associated with a greater risk of post-acute sequelae after SARS-CoV-2 infection, including long COVID, and downstream analyses implicated PAR-1 as a potential contributor to long COVID.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

This study demonstrates a femtosecond laser technique for imaging solvated oxygen atoms, offering an approach to investigate the behaviour of atomic radicals in liquid.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

High-throughput chemical ligand discovery is challenged by false positives. Here, authors introduce a scalable enantioselective affinity-selection mass spectrometry approach for proteome-wide ligand discovery with high sensitivity and selectivity

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Regrowth of lost enamel in tooth decay and sensitivity is a major obstacle to overcome. Here, the authors report on a protein-based material that mimics features of natural enamel formation, allowing for epitaxial growth of apatite nanocrystals to restore enamel structure and function.

The authors present a deep learning approach to uncover complex genetic effects on circulating protein levels. They reveal new interactions and dominance patterns using UK Biobank proteomics data.

In the phase 2 HUDSON study, patients with advanced non-small-cell lung cancer received anti-PD-L1 combined with biomarker-guided therapy targeting ATR kinase, PARP, STAT3 or CD73, leading to encouraging clinical benefit in response to combination of the ATR kinase inhibitor ceralasertib with durvalumab.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

The Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway mediates cellular responses to cytokines and growth factors, and its dysregulation plays a role in various disorders including autoimmune diseases, cancers and neurodegenerative disorders. This Review provides an overview of JAK–STAT signalling and discusses current and emerging strategies for therapeutic intervention, highlighting key challenges and new indications.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

A set of three papers in Nature reports a new proteomics resource from the UK Biobank and initial analysis of common and rare genetic variant associations with plasma protein levels.

Here, the authors report recent updates to the ENCODE data portal including a redesigned home page, an improved search interface, custom-designed pages highlighting biologically related datasets and an enhanced cart interface for data visualisation plus user-friendly data download options.

mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to immune checkpoint inhibitors.

Genomic and transcriptomic analysis of 393 non-small cell lung cancer patients treated with checkpoint inhibitors identifies molecular features associated with response.

Using data from 142,238 Mass General Brigham Biobank participants, researchers explored population history and social and genetic risk factors for disease in Greater Boston. The study links genetics and context to guide equitable precision health.

CAR-T cell therapy has been shown to be effective in immunotherapy for treatment of several different tumours. Here the authors show pre-specified interim outcomes from a P-BCMA-ALLO1 trial with BCMA targeted CAR-T therapy in multiple myeloma.

In an ongoing phase 1 trial, the combination of two new immunotherapies targeting CTLA-4 and PD-1 was overall well tolerated and elicited encouraging clinical responses in patients with relapsed/refractory microsatellite stable colorectal cancer, a tumor type typically unresponsive to immune checkpoint blockade.

Genome-wide analyses identify variants associated with sinus node dysfunction, distal conduction disease and pacemaker implantation, implicating ion channel function, cardiac developmental programs and sarcomeric structure in bradyarrhythmia susceptibility.

This Primer by Guttman-Yassky and colleagues reviews the epidemiology, pathophysiology, diagnosis and treatment of alopecia areata. This Primer also discusses the quality of life issues faced by patients and future research avenues.

Basal cells, rather than neuroendocrine cells, have been identified as the probable origin of small cell lung cancer and other neuroendocrine–tuft cancers, explaining neuroendocrine–tuft heterogeneity and offering new perspectives for targeting lineage plasticity.

A mathematical framework to estimate the fitness of cancer driver mutations by integrating mutational bias, oncogenicity and immunogenicity finds fundamental trade-offs in cancer evolution.

Treatment selection based on the presence of one or more specific biomarkers has the potential to optimize treatment outcomes; nonetheless, most patients lack a specific biomarker that is predictive of benefit from one or more targeted treatment approaches. In this Review, the authors describe the potential of computational analysis approaches to enable the discovery of more complex predictive biomarkers based on comprehensive analysis of large clinical and preclinical datasets and thus address this unmet need.

Here, Biswas et al. present and characterize a second-generation model of HBV infection in rhesus macaques, showing that extended infection requires suppression of host immunity.

The molecular characteristics of myocarditis associated with immune checkpoint inhibitors are described and potential biomarkers of onset and severity are identified.

The success of CAR T cell therapies against solid tumors remains limited. Here the authors report the results of a phase 1 trial of PSCA-directed autologous CAR-T cells with pharmacological activation by rimiducid in patients with metastatic pancreatic or prostate cancer.

Analyzing genetic data from over 210,000 Japanese individuals, the authors uncover 19 novel heart failure risk loci and develop a genetic score to predict those at high risk, revealing shared and ancestry-specific genetic bases across different populations.

NextBrain is an open source, probabilistic atlas of the entire human brain, assembled using artificial-intelligence-enabled registration and segmentation methods to reconstruct the multimodal serial histology of five human half brains, and which can be used to automatically segment brain MRI scans into 333 regions.

Izar and colleagues demonstrate that loss of Pip4k2c in melanoma cells promotes liver metastatic tropism driven by PI3K-AKT pathway activation in the insulin-rich liver milieu, which can be abrogated by inhibition of SGLT2 or a ketogenic diet.

Low frequency brain waves convey information between regions. Here, the authors demonstrate that for patients with major depression, mood becomes more negative as low frequency waves increase intensity  across the prefrontal cortex.

In the first stage of the BR.36 adaptive trial in patients with non-small cell lung cancer receiving anti-PD1 immunnotherapy, the primary endpoint of concordance between circulating tumor DNA (ctDNA) molecular response and RECIST response was met. The results will inform the second, ctDNA-directed stage.

An amphiphilic mimotope vaccine can be used in tandem with Food and Drug Administration (FDA)-approved CD19 CAR-T cell products.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Catalytic asymmetric a-alkylation of carbonyl compounds represents a longstanding challenge in synthetic organic chemistry but general methods for the catalytic symmetric alkylation of carbonyl compounds remain elusive. Here, the authors mine and engineer methyltransferases as synthetically useful biocatalysts for the catalytic asymmetric alkylation reactions of carbonyl compounds.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.