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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.

Drugs targeting cardiovascular disease (CVD) can have negative consequences for liver function. Here, the authors combine genome wide analyses on 69,479 individuals to identify loss-of-function variants with beneficial effects on CVD-related traits without negative impacts on liver function.

Due to their small size, atomic-scale Josephson junctions are vulnerable to thermal fluctuations. Escribano et al. show that introducing a delayed feedback element, a common method to mitigate thermal noise, induces spontaneous oscillations that enhance capabilities of Josephson microscopy.

Bosonic qubits can be engineered to feature intrinsic protection against certain kinds of errors, which makes quantum error correction across many bosonic qubits possible with less overhead.

AlphaFold 3 has a substantially updated architecture that is capable of predicting the joint structure of complexes including proteins, nucleic acids, small molecules, ions and modified residues with greatly improved accuracy over many previous specialized tools.

Targeted therapy is an important approach to reduce the side effects of medicinal drugs. This work reports the synthesis of catalytically active Pd nanostructures in exosomes that selectively target cancer cells for drug activation using biorthogonal chemistry.

Studies using mouse models of lung adenocarcinoma identify an association between age, iron homeostasis and tumour initiation potential that involves NUPR1 and lipocalin-2.

The authors find that structural economic inequality is linked to reduced brain volume and connectivity in middle-aged and older adults across the Americas, more so in Alzheimer’s disease than in frontotemporal dementia. The findings emphasize the biological embedding of inequality in aging and dementia.

A multicore analogue in-memory computing chip that is designed and fabricated in 14 nm complementary metal–oxide–semiconductor technology with backend-integrated phase-change memory can be used for deep neural network inference.

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.

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.

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.

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.

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

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.

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.

In June 2022, the IXPE satellite observed a shock passing through the jet of active galaxy Markarian 421. The rotation of the X-ray-polarized radiation over a 5-day period revealed that the jet contains a helical magnetic field.

Alternative stable states in forests have implications for the biosphere. Here, the authors combine forest biodiversity observations and simulations revealing that leaf types across temperate regions of the NH follow a bimodal distribution suggesting signatures of alternative forest states.

The global ecological predictors of soil priming remain unclear. Here the authors conducted a global survey of soils from 86 global locations using an isotopic approach and find that in more mesic sites with high SOC concentrations, soil priming effects are more likely to be negative.

Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

In this Consensus Statement, an international panel of experts present an overview of the latest developments in the field of cholangiocarcinoma. A set of consensus recommendations and research priorities is provided.

There is a pressing need for therapeutic agents against Zika virus (ZIKV). Here the authors present cryoEM structures of a neutralizing antibody (C10) complexed with ZIKV that show C10 preventing structural changes required for virus entry into the cell, suggesting it might be effective in treating Zika infections.

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.

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 rate of Arctic coastal permafrost erosion is predicted to increase up to 3 times by 2100. Here the authors model how organic matter released from coastal permafrost erosion will reduce the CO₂ sink capacity of the Arctic Ocean and lead to positive feedbacks on climate.

Machine learning models showed that social disparities, cardiometabolic disease and mental health were the main predictors of aging in Latin American populations, with these factors being more pronounced in low- and middle-income compared to high-income Latin American countries.

Most genetic studies have been done on European cohorts, which affects the efficacy of polygenic risk scores in non-European populations. Here, the authors demonstrate that a colorectal cancer PRS including Asian and European ancestries has improved performance over the European-centric PRS across racial and ethnic groups.

The large virus family,Paramyxoviridae, includes several human and livestock viruses. This study, testing 119 bat and rodent species distributed globally, identifies novel putative paramyxovirus species, providing data with potential uses in predictions of the emergence of novel paramyxoviruses in humans and livestock.

Immune disease-associated biomarker values are commonly more variable in affected compared to unaffected patient populations, which limits a biomarker’s informative range. Here, the authors formalise a computational solution that splits datasets into informative and uninformative subsets to improve biomarker discovery and performance of multivariate predictive models.

Repetto et al. provide an analysis of the genetic basis of variation of neuro-related protein levels in plasma and link this to human behaviour and disorders.

Multiomic factor analysis of blood multiomic data, including single-cell transcriptomics, for individuals with either acute or chronic coronary syndrome identifies immune cell signatures that correlate with treatment outcomes.

Integrating inventory data with machine learning models reveals the global composition of tree types—needle-leaved evergreen individuals dominate, followed by broadleaved evergreen and deciduous trees—and climate change risks.

The influence of climate on premodern civil conflict and societal instability is debated. Here, the authors combine archeological, historical, and paleoclimatic datasets to show that drought between 1400-1450 cal. CE escalated civil conflict at Mayapan, the largest Postclassic Maya capital of the Yucatán Peninsula.

This study presents a chloroplast photosystem I structure identified by cryogenic electron microscopy from the green alga Chlamydomonas reinhardtii. In contrast to the cyanobacterial complex, the absence of PsaH and Lhca2 allows a head-to-head orientation of the photosystem I–light-harvesting complex I monomers.

The authors analyse tree responses to an extreme heat and drought event across South America to understand long-term climate resistance. While no more sensitive to this than previous lesser events, forests in drier climates showed the greatest impacts and thus vulnerability to climate extremes.

Although progress in the coverage of routine measles vaccination in children in low- and middle-income countries was made during 2000–2019, many countries remain far from the goal of 80% coverage in all districts by 2019.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

Clinical studies have suggested that the therapeutic potential of polyclonal convalescent plasma is highest in the first days of symptoms. Here, the authors present results from a pooled analysis of two clinical trials in COVID-19 outpatients that did not provide conclusive evidence in favor of convalescent plasma.

Most Amazon tree species are rare but a small proportion are common across the region. The authors show that different species are hyperdominant in different size classes and that hyperdominance is more phylogenetically restricted for larger canopy trees than for smaller understory ones.

Evaluation of a nanopore-sequencing-based workflow for detection of antimalarial resistance in Ghana demonstrates feasibility where molecular surveillance is needed.