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Different types of SETBP1 variants cause variable developmental syndromes with only partial clinical and functional overlaps. Here, the authors report that SETBP1 variants outside the degron region impair DNA-binding, transcription, and neuronal differentiation capacity and morphologies.

An ensemble of spins from nitrogen–vacancy centres in diamonds is prepared in a spin-squeezed state.

Experiments under upper-tropospheric conditions map the chemical formation of isoprene oxygenated organic molecules (important molecules for new particle formation) and reveal that relative radical ratios control their composition

Trained and validated on multimodal data from 14.5 million images from multicountry datasets, a foundation model is shown to increase diagnostic and referral accuracy of clinicians when used as an assistant in a trial involving 16 ophthalmologists and 668 patients.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder characterized by the functional loss of the tumor suppressor gene neurofibromin, that can lead to the development of benign and malignant tumors. Here the authors describe the development of an adeno-associated virus vector for NF1 gene replacement therapy of NF1 related tumors, showing tropism and anti-tumor activity in preclinical models

The molecular landscape of Fibrolamellar Hepatocellular Carcinoma (FLC), a rare liver cancer, remains to be characterised. Here, multi-omics analysis of liver tumours across different liver cancer subtypes identifies distinct transcriptomic signatures and reveals that PKA activation is the unifying phenotype of FLC.

Using mouse pancreatic cancer models, Tsanov et al. show that reactivation of SMAD4 at metastatic sites promotes tumor growth in the lung through RUNX1 but restrains metastatic growth through KLF4 in the liver, influenced by organ-specific epigenetic states.

Programmable topological dipoles could be used in stimuli-responsive materials. Now it is shown that confinement of an apolar liquid crystal results in controllable polar arrangements of elastic dipoles.

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.

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

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

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.

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.

An NNMT inhibitor reduces tumour burden and metastasis in multiple mouse cancer models and restores immune checkpoint blockade efficacy by decreasing cancer-associated-fibroblast-mediated recruitment of myeloid-derived suppressor cells and reinvigorating CD8⁺ T cell activation.

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.

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.

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.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

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.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

The efficient separation of chiral molecules is a fundamental challenge in the manufacture of pharmaceuticals and light-polarising materials. Here, the authors develop an approach that combines machine learning with a physics-based representation to predict resolving agents for chiral molecules, using a transformer-based neural network.

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.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

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.

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.

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.

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 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.

Estimates from the Global Dietary Database indicated that 2.2 million new type 2 diabetes and 1.2 million new cardiovascular disease cases were attributable to sugar-sweetened beverages worldwide in 2020, with the highest burdens in sub-Saharan Africa, Latin America and the Caribbean.

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.

Yang, Jn-Simon, He et al. report that the dual BCL-xL/BCL-2 PROTAC 753b is a potent and liver-tropic senolytic, which (unlike other inhibitors of BCL-xL) does not cause severe thrombocytopenia. They evaluate its efficacy in natural aging and in reducing progression from steatotic liver disease to hepatocellular carcinoma, using mouse models.

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.

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.

Fatty liver disease exacerbates atherosclerosis, but the underlying mechanisms remain unclear. Here, the authors show that D-dopachrome tautomerase (D-DT/MIF-2) acts as an atypical chemokine, promoting both atherosclerosis and hepatic lipid accumulation.

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.

Lattice mismatches are a difficult obstacle in the formation of core-shell heterostructures. Here, the authors develop a strategy to overcome the lattice mismatch and grow α-phase lead halide perovskites onto β-phase lanthanide-doped nanoparticles.

This study maps individual trees across 54 African cities to examine the relationship between tree cover and urban informality. The findings highlight a shortage of green infrastructure in informal settlements and the need for data-driven strategies to integrate trees into future urban development.

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).

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.

The largest harmonized proteomic dataset of plasma, serum and cerebrospinal fluid samples across major neurodegenerative diseases reveals both disease-specific and transdiagnostic proteomic signatures, including a robust plasma profile associated with the APOEε4 genotype.

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.

Second-generation oxidation boosts the production of anthropogenic organic aerosol, according to an analysis of urban haze in an experimental chamber.