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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).

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

MAASTY, a methacrylic acid–styrene copolymer, enables high-resolution structural determination of human membrane proteins in native nanodiscs, efficiently solubilizing diverse membrane proteins and preserving endogenous lipids for structural and functional studies.

The study shows that gyre-scale ocean dynamics, driven by wind stress curl anomaly, were the main cause of the 2013-15 and 2019-20 northeast Pacific marine heatwaves via poleward warm water advection, while surface heat fluxes explain their decay.

Using the well-established foundry-based lithium niobate nanophotonics platform, a general electro-optic digital-to-analogue link with ultrahigh bandwidth (>150 Gb s⁻¹) and ultralow power consumption (0.058 pJ b⁻¹) is demonstrated, providing a direct, energy-efficient, high-speed and scalable solution for interfacing digital electronics and photonics.

Spectroscopic signatures of magnetic response in topological materials remain very limited. Here, the authors observe a quasi-linear field dependent transverse magnetization and a non-saturating parallel magnetization in a Weyl semimetal TaAs under strong magnetic field, suggesting a signature of relativistic quasiparticles in topological materials.

Primary CoronaVac vaccination followed by a BNT162b2 booster dose confers protection against some SARS-CoV-2 variants but its effectiveness against Omicron is unknown. Here, the authors show that this combination confers a high level of protection against severe outcomes for up to 120 days, with evidence of waning for those aged 80 or older.

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.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Perineural invasion and cancer-induced nerve injury of tumour-associated nerves are associated with poor response to anti-PD-1 therapy, which can be reversed by combining anti-PD-1 therapy with anti-inflammatory interventions.

Although China leads the pack, fast-moving institutions are building their research reputations the world over.

To address an evidence gap for the efficacy of hypertension therapy using dual drug combinations in patients of South Asian origin, a randomized clinical trial conducted in India found that three types of dual drug combinations, each administered in a single pill, had similarly large effects on reducing blood pressure.

Proteoforms are the diverse protein molecules produced from a single gene whose primary sequence and composition can be diversified by genetic, transcriptomic, translational and post-translational variation. This Review synthesizes technologies and network approaches to map, quantify and functionally characterize proteoforms, outlining routes to proteoform-guided biomarkers and therapeutics

A parity–time symmetric system based on two coupled acoustic resonators in a lithium niobate platform can achieve non-reciprocal propagation of acoustic waves.

Conventional PROTACs have limited capacity for misfolded proteins. Here, authors develop a BioPROTAC containing an scFv specifically targeting misfolded SOD1, fused to an E3 ligase, and demonstrate a strategy for reducing misfolded SOD1 accumulation.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

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

Lv et al. discover that homologous disordered regions of proteins linked to ALS/FTD and Parkinson’s, CHCHD10 and CHCHD2, form amyloid fibrils in vitro and that the structures of these fibrils are consistent with potential roles for them in disease.

The authors develop a strategy that allows the diffusion limit of ions in water to be approached for large-area, free-standing, synthetic membranes using covalently bonded polymer frameworks with rigidity-confined ion channels.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

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.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

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.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Psoriasis is a partially heritable skin disorder, the genetic basis of which is not fully understood. Here, the authors use genome-wide association meta-analysis to discover psoriasis susceptibility loci and genes, which encode existing and potential new drug targets.

There is limited evidence of the effectiveness of the CoronaVac vaccine for children against the Omicron SARS-CoV-2 variant. Here, the authors use data from Brazil for children aged 6–11 years and estimate effectiveness of 40% against infection and 59% against severe disease at least two weeks after the second dose.

‘Smart cities’ seek to maximize connectivity to improve urban mobility.

The oldest sepioid in the Cretaceous shows intermediate morphologies between cuttlefish and bobtail squids, revealing their early evolution. This discovery was facilitated by Digital fossil-mining method incorporating a zero-shot learning AI model.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Conditional ablation experiments show that key components of the synaptonemal complex protect double Holliday junction recombination intermediates to ensure their resolution into crossover products, which are required for accurate chromosome segregation during meiosis.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

BamA is the catalytic core of the BAM complex, which inserts proteins into bacterial outer membranes. Here, the authors show that hinge flexibility between BamA’s β-barrel and POTRA domains is vital, demonstrating how evolution has fine-tuned the BamA sequence and structure for function.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

This study reports unexpected structural diversity in computationally designed protein assemblies due to subunit flexibility. Fixing flexibility in one design restores the intended architecture, suggesting a strategy to design dynamic assemblies.

Chen, Neil, Tan, Rudraraju et al. use an induced trophoblast stem-cell-based model of SARS-CoV-2 infection and identify syncytiotrophoblasts as the cells targeted by the virus in the early placenta.

Using ultraviolet data as well as a comprehensive set of further multiwavelength observations of the supernova 2023ixf, a reliable bolometric light curve is derived that indicates the heating nature of the early emission.