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This multidisciplinary response to investigate the large outbreak of unknown febrile illness in the Panzi Health Zone in the Democratic Republic of the Congo in late 2024 suggests that the outbreak was largely associated with malarial cases and concurrent viral respiratory infections.

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.

Wang et al. analyzed data from the Detroit Neighborhood Health Study to explore links between social adversity, post-traumatic stress and epigenetic regulation through blood-derived micro-RNA profiles.

Most GWAS have focused on common variants or rare protein coding variants. Here, the authors interrogate the contribution of rare non-coding variants for anthropometric traits, identifying new genes associated with increased BMI and height.

Here, the authors conduct a GWAS for eGFR, then a three-stage regional meta-analysis using GWAS summary data from the Eastern, Western, and Southern African geographical regions. Followed by fine mapping, colocalization, functional annotation, pathway analysis, and phenome-wide association studies showing weaker APOL1 effects in Africa.

This study analyses whole-genome sequencing data of cancer samples from 10,983 patients and explores relationships among mutational signatures, various biomarkers and clinical outcomes.

Cholera remains a significant public health burden in sub-Saharan Africa, but the mechanisms of continental and regional spread remain undefined. Here, the authors investigate recent patterns of spread using Vibrio cholerae genomic surveillance data collected by a consortium of seven African Union member states from 2019-2024.

Saturation genome editing of a cancer mutation hotspot in CTNNB1, the gene encoding β-catenin, reveals a gradient of effects of missense mutations on Wnt signaling.

Single-molecule chromatin fiber sequencing exposes single-cell-level heterogeneity in the chromatin architecture of individual regulatory elements.

CLASSIC is a high-throughput genetic profiling platform that combines long- and short-read next-generation-sequencing modalities to quantitatively assess pools of constructs of arbitrary length containing diverse genetic part compositions.

Given rising diabetes prevalence globally, access to diabetes treatments is gaining urgency. Here, the authors show patterns of glucose-lowering medication use for diabetes across 62 low- and middle-income countries.

Schizophrenia is a complex brain disorder with its underlying protein changes generally not well understood. Here, authors show widespread alterations in the prefrontal cortex, marked by reduced energy production and disrupted synaptic function.

A multiancestry phenome-wide analysis of copy number variants in the UK Biobank genomes increases power to detect genetic associations with complex traits across human populations.

A platinum(II) azido complex (complex 1) that releases platinonitrene upon X-ray exposure induces DNA damage and enhances immune checkpoint blockade outcomes via the abscopal effect.

In a randomized controlled study involving 1,298 participants from a general sample, performance of humans when assisted by a large language model (LLM) was sensibly inferior to that of the LLM alone when assessing ten medical scenarios leading to disease identification and recommendations for treatment.

A M5 earthquake triggered the 2018 Sierra Negra eruption after 10 hours. Subsequent microseismicity revealed a cryptic fluid phase facilitated magma intrusion, highlighting that cascading processes are potentially essential for eruption initiations.

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.

This Resource paper presents a global SARS-CoV-2 phylogenetic tree of 4,471,579 high-quality genomes consistently constructed by Viridian, an efficient amplicon-aware assembler.

The authors present a genetically encoded tool based on a bifunctional enzyme that can regenerate NAD⁺ while executing an engineered glycerol shunt. The tool successfully restored redox imbalance and modulated lipid metabolism in vitro and in a mouse hepatic steatosis model.

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

Achieving tight Cas9 regulation without sacrificing activity remains difficult. Here, the authors design multi-level circuits combining anti-CRISPRs, splice sites, chemical induction, and degron control to enable ultra-high dynamic range and precise, on-demand genome editing across contexts.

AlphaGenome, a deep learning model that inputs 1-Mb DNA sequence to predict functional genomic tracks at single-base resolution across diverse modalities, outperforms existing models in variant effect prediction and enables comprehensive genomic analysis.

This work introduces a pedigree-derived benchmark for single-nucleotide variants, indels, structural variants and tandem repeats, offering a variant map to validate sequencing workflows or to support the development and evaluation of new variant callers.

Juvenile idiopathic arthritis (JIA) associated uveitis can cause vision loss in children, but mechanisms remain unclear. The authors here identify elevated CD19⁺IgD^-CD27^- double negative type 1 B cells in JIA-uveitis and show that targeting B-T cell interactions suppresses disease in mouse models of uveitis.

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.

Heparan sulfate proteoglycans facilitate the assembly of clusters of glycoRNAs and cell surface RNA-binding proteins, which negatively modulate VEGF-A signalling and angiogenesis.

Five-year survival data and biomarker analysis of the PRADO extension cohort of the phase 2 OpACIN-neo trial, in which patients with high-risk stage III melanoma received neoadjuvant ipilimumab and nivolumab and underwent pathologic response-directed surgery and adjuvant therapy, show 71% event-free survival and 88% overall survival, with tumor mutational burden, IFNγ signature and PD-L1 expression associated with favorable outcomes.

De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

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.

Colorectal cancer is often diagnosed at later stages, leading to poor prognosis. Here, the authors utilise analysis of rectal mucus specimens using host and microbial analysis to detect cancer lesions.

Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibitors in mixed-lineage leukaemia.

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.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

Newly developed mouse models that enable cell-specific analyses of proteostasis dynamics across the lifespan of the mice reveal key aspects of neuronal proteostasis with ageing.

An anti-HIV-1 antibody that targets an N332_gp120 glycan-independent V3 epitope, a site of Env vulnerability, can decline viremia in HIV-1-infected humanized mice while overcoming classical V3 escape mutations.

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.

Electrons can seem electrically neutral in some devices. Neutral states can be distinguished in real time by a measure of their electron pairing called odd or even parity.

Npm1 promotes tumor formation via attenuating the integrated stress response and p53 activation in mouse WNT-driven intestinal and liver tumorigenesis.

Transcription factor osr2 is identified as a specific marker and regulator of mural lymphatic endothelial cell (muLEC) differentiation and maintenance, and muLECs and border-associated macrophages share functional analogies but are not homologous, providing an example of convergent evolution.

Whole-genome sequencing of polioviruses in Uganda following nOPV2 use showed high genetic stability and no sustained transmission, even though a rare double recombinant strain regained virulence, but did not spread due to high vaccination coverage.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

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.

Microflora Danica—an atlas of Danish environmental microbiomes—reveals that although human-disturbed habitats have high alpha diversity, species reoccur, revealing hidden homogeneity.

DNA variant calling methods based on deep neural networks can use local haplotyping information with long-reads to improve genotyping accuracy, however this increases computational complexity. Here the authors develop an approximate haplotagging method that simplifies the process and enables state-of-the-art variant calling performance with multiple sequencing platforms.

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.

Complex structural variations and rearrangements in cancer are identified using long-read sequencing.

The PCRCR complex of Plasmodium spp. binds basigin on the erythrocyte surface. While Rh5 of the complex is restricted to P. falciparum, PTRAMP, CSS and Ripr orthologs are present across the genus, for which the authors report common features.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Elevated levels of IL-33 induce the production of autoantibodies through an unknown mechanism. Here, the authors show that IL-33 disrupts splenic architecture and germinal center organization, causing an expansion of antibody-secreting plasmablasts and plasma cells. In multiple mouse models of inflammation, administration of IL-33 exacerbates the pathology, increasing the production of autoantibodies, whereas IL-33 blockade reverses autoantibody production in a model of lung inflammation.

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).