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Crosslinking mass spectrometry offers direct PPI mapping but suffers from low yields. Here, the authors develop a two-step click-linking strategy that improves crosslinking efficiency and interactome coverage in fixed cells, outperforming conventional methods.

Approaches making virtual and experimental screening more resource-efficient are vital for identifying effective inhibitors from a vast pool of potential drugs but remain elusive. Here, the authors address this issue by developing an active learning framework leveraging high-throughput molecular dynamics simulations to identify potential inhibitors for therapeutic applications.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

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.

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.

Dopamine encoding of reward prediction errors naturally fluctuates over females’ reproductive cycles with estrogenic signaling due to reduced expression of dopamine reuptake proteins.

Synovial sarcoma (SS) is a difficult-to-treat cancer, driven by the fusion oncoprotein SS18::SSX. SS18::SSX alters the BAF (mammalian SWI/SNF) chromatin remodelling complex to create an oncogenic transcriptome. Here, the authors identify SS18::SSX-driven SMARCE1 SUMOylation as a therapeutic vulnerability in SS and show that SUMOylation inhibition stabilizes the cBAF complex, inducing cell death and sensitization of SS to chemotherapy.

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.

There is still a need for effective HIV vaccines. In this phase I clinical trial, the authors show that an HIV-1 vaccine candidate, ConM SOSIP.v7, is well-tolerated in HIV-negative adults and that it elicits a strain-specific neutralising antibody response that differed between female and male participants.

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.

This work presents a fully implantable wireless optogenetic device that delivers spatiotemporally patterned cortical stimulation through the skull and generates artificial perception in mice.

Pilcher et al. present a single-cell transcriptomics-based immune atlas of participants with newly diagnosed multiple myeloma, reporting on the association of cell types, gene expression and intercellular interactions with disease progression phenotypes.

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.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

Data provided by Amazonian peoples are used to estimate the value of wild animals as a source of food, including its spatial distribution and nutritional value, providing information that will be key for improved management of forest ecosystems in the region.

Wang, Xiao and colleagues develop and validate organ-specific proteomic aging clocks across large population cohorts in the UK, the USA and China, which show strong performance in tracking organ aging and predicting the risk of morbidity and mortality.

α/β-hydrolase domain-containing protein 11 (ABHD11) is a mitochondrial hydrolase, and its expression in CD4 + T-cells has been linked to remission status in rheumatoid arthritis. Here the authors report that pharmacological inhibition of ABHD11 modulates T-cell effector function via increased 24,25-epoxycholesterol biosynthesis and subsequent liver X receptor activation.

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.

Mass-wasting deposits that accumulated against mid-ocean ridge faults have high porosity in which calcium carbonate precipitated, storing seawater carbon dioxide, as revealed by cores of a 61-million-year-old seafloor talus deposit.

Using terahertz spectroscopy and ultrafast electron diffraction, the paper shows how the DC conductivity of warm dense matter depends on material phase. This provides insight to how electron scattering processes impact conductivity in this regime.

An operational satellite-based monitoring system using NASA/USGS and ESA imagery enables rapid tracking of global land change, with the area of conversion due to direct human action and fire equaling the size of California in 2023.

The authors couple calculations of historical heatwave intensity at present and future global temperatures with exposure–response functions to quantify mortality from extreme heat events in Europe. They project tens of thousands of excess deaths, with limited attenuation from existing adaptations.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

Genome-wide association analysis in over one million individuals of European ancestry identifies 2,103 independent genetic signals (including 113 new loci) associated with blood pressure traits.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

A transverse Peierls transition can occur when transverse acoustic phonons couple with conducting p-orbital electrons. Here, the authors observe an incommensurate transverse Peierls transition and signatures of a chiral charge density wave in EuAl₄.

The low-density lipoprotein receptor family members LRP1, LRP4 and VLDLR are entry receptors for yellow fever virus.

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.

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.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

The role of cohesion is vital to our understanding of how sedimentary bedforms evolve. Here, the authors show that microorganisms within the sediment affect cohesion and demonstrate that ripples can take up to one hundred times as long to develop when extracellular polymeric substances are present.

Parallel operation of two exchange-only qubits consisting of six quantum dots arranged linearly is shown to be achievable and maintains qubit control quality compared with sequential operation, with potential for use in scaled quantum computing.

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.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Understanding of the immune microenvironment in pediatric acute T cell lymphoblastic leukemia is limited. By analyzing single-cell transcriptome, surface protein expression and immune repertoire data, the authors here identify non-malignant CD4^-CD8^- TCRαβ T cells that are present in a subset of patients with Rap1 signaling in leukemia cells and are associated with adverse clinical outcome in patients with low minimal residual disease.

In a post-hoc analysis of circulating tumor DNA (ctDNA) features from patients with metastatic prostate cancer treated with [¹⁷⁷Lu]Lu–PSMA-617 or cabazitaxel in the randomized phase 2 TheraP trial, low ctDNA levels at baseline were predictive of clinical benefit from [¹⁷⁷Lu]Lu–PSMA-617, and PTEN or ATM alterations were identified as potential biomarkers of response.