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This study introduces the Lipid Nanoparticle Database (LNPDB) and web tool that consolidates lipid nanoparticle structure-function data. LNPDB facilitates molecular dynamics and deep learning approaches to advance data-driven design for nucleic acid delivery.

Rice paddies contribute to atmospheric methane (CH₄) levels. Here the authors show that increasing levels of the rice plant hormone PSY can reduce CH₄ emissions by over 50% via alteration of microbial H₂ cycling in the rhizosphere.

Pangenomic and epidemiological analyses reveal a genetic shift in U.S. Salmonella Hadar populations during 2019–20, driven by expansion of a lineage carrying a prophage-like element that likely arose in commercial poultry and spread to backyard flocks.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Early identification of high-risk trauma patients in prehospital settings is essential for effective triage and improved survival. Here the authors show that a real-time ensemble AI model accurately predicts emergency department mortality using only prehospital data, outperforming traditional triage tools.

Asexual-to-sexual switching underpins malaria transmission. Prajapati et al. identify an AP2-G loss-of function mutation and use it as a genetic tool to show that GDV1 is essential for initial ap2-g activation and sexual commitment initiation.

Epstein–Barr virus (EBV) is a widespread herpesvirus linked to cancer and autoimmune disease. The authors in this work design and characterize a stabilized prefusion form of gB, an essential viral fusion protein, advancing EBV vaccine and therapeutic development.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Human impacts on marine ecosystems are increasing the likelihood of pathogenic outbreaks, harmful algal blooms and coral stress. Here the authors develop a CRISPR biomonitoring tool that can help detect key marine species that are important to public health, the aquaculture sector and marine ecosystems.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

In a phase 2 trial evaluating healthy donor fecal microbial transplantation plus either anti-PD-1 in patients with non-small cell lung cancer or anti-PD-1 and anti-CTLA-4 in patients with melanoma, encouraging efficacy was seen in both cohorts, with responses linked to significantly greater loss of baseline bacterial species.

Kidney organoids derived from human pluripotent stem cells are infused in a normothermic machine perfusion system to condition explanted porcine kidneys, and the feasibility and viability of their in vivo engraftment are demonstrated.

Challenges in mapping modern molecular and anatomical datasets into a common atlas are not fully addressed. Here authors present approaches to aligning multimodal neuroimaging data and quantifying geometric variability. Authors also make sure open-source code, dataset standards, and a web interface are available, enabling large scale integration of datasets essential to modern neuroscience.

Hepatocyte organoids derived directly from human tissue enable long-term hepatocyte expansion and can be combined with portal mesenchyme and cholangiocyte organoids to form a donor-specific periportal liver assembloid system.

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.

Kang, Lazo de la Vega et al. introduce iCatalog, a precision oncology reporting tool developed to address the needs of a large multi-institutional pediatric study. iCatalog combines a database for patient, sample, and genomic data to enable clinical interpretation of patient-level tumor profiling results.

Urinary kidney injury-1 (Kim-1) outperforms serum creatinine, blood urea nitrogen and urinary N-acetyl-β-D-glucosaminidase in detecting kidney damage induced in rats by a range of nephrotoxicants. Earlier detection of renal injury, enabled by monitoring levels of urinary Kim-1, should enable elimination of nephrotoxic candidates sooner in the drug development pipeline.

There is a need for an easy-to-use clinical tool, that could predict favorable early PSA response and subsequently enhance early risk stratification, as well as guide treatment planning. Here, the authors show that based on patient data from four phase III randomized trials, Nadir androgen receptor pathway inhibitor (APRI)- Derived Integrative Response (NADIR) model predicts favorable early PSA response to ≤0.2 ng/mL by 6 months in metastatic hormone sensitive prostate cancer (mHSPC) patients initiating treatment with an APRI.

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.

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.

Engineered carbon nanotube sensors enable the detection of intracranial tumours in blood, identify low-abundance biomarkers and amplify cancer detection by capturing secreted factors from the entire tumour ecosystem for early-stage disease diagnosis.

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.

The evolution of cutaneous squamous cell carcinoma (cSCC) remains poorly understood. Here, the authors employ multi-omics and multi-scale analyses to explore the genetic evolution of keratinocytes to cSCC, finding key pathogenic mutations that break the resistance to ultraviolet radiation as well as spatial heterogeneity patterns.

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.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

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.

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.

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.

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.

Gubela et al. calibrate an adaptive agent-based model with intra-host dynamics to investigate the 2022 Mpox outbreak dynamics in Berlin. Behavioral change and infection-induced immunity are the main reasons for outbreak decline, while the effect of vaccination is marginal.

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.

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.

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.

Genetically encoded sensors are generally optimized to function during exponential growth rather than stationary phase, which limits their potential value for metabolic engineering and bioproduction. Here, authors engineer a stationary phase green light sensor and use pulsatile light to optimize production of industrially relevant small molecules.

Long COVID has heterogeneous presentation and clinical trajectories are not well defined. Here, the authors define trajectories using data from a prospective cohort study in the United States involving symptom questionnaires from acute infection up to 15 months.

A panel of urinary biomarkers enables the progression of renal injury and subsequent repair and recovery to be monitored after exposure of rats to either carbapenem A or gentamicin. The authors complement this study by demonstrating that serum cystatin C is more sensitive and specific than serum creatinine and blood urea nitrogen in monitoring generalized renal function after exposure to nephrotoxicants.

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.

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.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

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 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 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.