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In a large multi-ethnic Asian cohort, associations between over 1,000 plasma metabolites and specific foods and beverages are made. These diet–metabolite relationships were used to accurately predict clinical phenotypes such as diabetes and hypertension.

Natural Killer cells are key mediators of anti-tumour immunosurveillance and anti-viral immunity. Here, the authors map regulatory genetic variation in primary Natural Killer cells, providing new insights into their role in human health and disease.

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.

Mapping of spatial metabolic gradients in the mouse liver and intestine identifies fructose-induced focal derangements in liver metabolism.

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.

An optical detection and analysis platform quantifies aggregate density, distribution and size in fluorescently labelled post-mortem human brain tissue.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

A 1,024-channel microelectrode array is delivered to the brain cortex via a minimally invasive incision in the skull and dura, and allows recording, stimulation and neural decoding across large portions of the brain in porcine models and human neurosurgical patients.

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 genome-wide CRISPR screen helps to identify the Epstein–Barr virus receptor desmocollin 2 for primary epithelial cell infection. Additional infection assays revealed that desmocollin 3 also aids infection.

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.

TCR-TRANSLATE, a deep learning framework adapting machine translation to immune design, demonstrates the successful generation of a functional T cell receptor sequence for a cancer epitope from the target sequence alone.

The GPS Pipeline enables accessible and scalable genomic surveillance of Streptococcus pneumoniae. It performs quality control and in silico typing of sequencing reads with high accuracy using a single simple command, without requiring the internet.

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 transcription factors TCF1 and LEF1 promote self-renewal and regulatory functions in B-1a cells.

Drug resistance in bacteria often involves drug-tolerant persisters. Mycobacterium tuberculosis uses trehalose catalytic shift to promote persister formation, thereby developing multidrug resistant-TB (MDR-TB). Authors show that inhibiting this shift reduces MDR-TB, highlighting a potential therapeutic target for new treatments.

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.

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

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

Alterations of therapeutic pressures have been shown to affect clonal evolution of resistance. Here, the authors conducted a single arm, phase 2 trial consisting of alternating osimertinib and gefitinib in non-small cell lung cancer, and found ctDNA dynamics were predictive of response.

A population of TRAIL-positive astrocytes in glioblastoma contributes to an immunosuppressive tumour microenvironment and this mechanism can be targeted with an engineered oncolytic virus to improve outcomes.

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.

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).

In strongly correlated systems, how magnetic excitations are renormalized by charge carriers remains an open question. An experiment now reports the observation of magnon-polarons—magnons dressed by doped holes—in a Fermi–Hubbard quantum simulator.

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.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

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.

The authors show that ~100-kyr climate cycles over the past ~800 ka, and even since ~34 Ma, likely arose from a ~2.4-Myr eccentricity-modulated competition between low- and high-latitude continental carbon reservoirs for dominance in carbon cycles.

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.

Long non-coding RNAs are identified as non-invasive biomarkers predicting homologous recombination deficiency and PARP inhibitor sensitivity in high-grade serous ovarian cancer, enabling improved precision oncology approaches.

An optically addressable fluorescent-protein spin qubit is realized using enhanced yellow fluorescent protein; the qubit can be coherently controlled at liquid-nitrogen temperatures and the spin detected at room temperature in cells.

SCIFER detects clonal selection in whole-genome sequencing data using a population genetics model. Applied to a range of somatic tissues, SCIFER quantifies stem cell dynamics and infers clonal ages and sizes without requiring knowledge of driver events.

Certo, Pontarini et al. provide insight into the metabolic requirements of ectopic lymphoid structure (ELS) assembly in the context of autoimmunity, and show that blocking lactate uptake by SLC5A12 offers therapeutic benefits in a mouse model of Sjögren’s disease.

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.

ANCA-associated vasculitis (AAV) includes three disease subtypes with partly overlapping clinical manifestations: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). This Review article provides an update on the diagnosis and classification of AAV, discussing parameters for assessing disease activity and predicting outcomes towards a personalized medicine approach.

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.

A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.

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.

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.

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.

DeepRETStroke is a deep learning system using retinal photographs to detect silent brain infarction and predict future stroke events.

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.

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.

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.

Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional approaches, while also offering potential new insights beyond standard genetic analyses.

Using a combination of radical retrosynthesis, biocatalysis and C–H functionalization logic, a concise and scalable approach to the synthesis of saxitoxin and derivatives thereof in fewer than ten steps is presented.