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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.

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.

C. elegans aggregate in large clumps during feeding. Here, the authors find conserved autism-associated genes mediate distinct molecular and circuit signaling components that tune C. elegans feeding behavior from solitary to social feeding.

Homologous recombination ensures chromosome segregation and genetic diversity. Here, the authors reveal a role for the Hop2-Mnd1 complex in maintaining Dmc1-mediated recombination fidelity by preventing illegitimate DNA exchanges.

Energy transfer between fluorophores is shown to impede SMLM at sub-10-nm spatial resolution. Time-resolved detection and photoswitching fingerprinting analysis are used to determine the number and separation of closely spaced fluorophores.

Arteries are vital blood vessels for our body and their growth and patterning are critical for proper blood flow. Here they use a retina model to show that a balance of EphB4 receptor and ephrin-B2 ligand integrate a well-wired molecular network to control arteriovenous patterning and vascular growth.

A small molecule enhances targeted gene integration at therapeutically relevant loci in human primary cells.

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.

Analyses of microbial communities that live 10–750 m below the seafloor at Atlantis Bank, Indian Ocean, provide insights into how these microorganisms survive by coupling energy sources to organic and inorganic carbon resources.

Electrocorticographic recordings in 10 patients show that stimulus response and repetition suppression are temporally, spatially, and spectrally distinct.

Analysing camera-trap data of 163 mammal species before and after the onset of COVID-19 lockdowns, the authors show that responses to human activity are dependent on the degree to which the landscape is modified by humans, with carnivores being especially sensitive.

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).

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.

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

Genome mining for biosynthetic gene clusters (BGCs) can be used for the discovery of new compounds of biotechnological interest. Here, the authors use metagenomics and metatranscriptomics to identify diverse BGCs in free-living and particle-associated microbial communities through the stratified water column of the Cariaco Basin, Venezuela.

A multidimensional proteomics analysis of the interactions between around 2,000 nuclear proteins and over 80 modified dinucleosomes representing promoter, enhancer and heterochromatin states provides insights into how chromatin states are decoded by chromatin readers.

An analysis of single-cell RNA sequencing data from adult and developing lungs across vertebrate species reveals genetic components in the common ancestor of jawed vertebrates and new lung-specific enhancers that contribute to the evolution of vertebrate lungs.

Immune checkpoint inhibitors with or without chemotherapy are now standard of care for non-small cell lung cancer. However, the benefits of combination vs sequential therapy have not been fully explored. Here, the authors analysed 1,133 patient records and show combination therapy showed increased protection against early progression, but similar overall survival.

Symbiotic nitrogen fixation is a tightly regulated process serving as a sustainable source of nitrogen (N) in agriculture. Here it is shown that external N sources precisely regulate N fixation efficiency by modulating iron transport in nodules of legumes.

Correlated disorder can lead to phenomena that are inaccessible to ordered structures. Here the authors show that local order principles can be directly derived from the three-dimensional difference pair distribution function based on the single crystal diffuse scattering in 3D electron diffraction data from nanometre sized crystals.

Rational design was used to develop a suite of red-shifted, bioconjugatable heptamethine cyanine dyes for multiplexed in vivo imaging in the shortwave-infrared/near-infrared-II region.

Hofer et al. show that fasting promotes the synthesis of spermidine, which stimulates eIF5A hypusination to induce autophagy and increase lifespan in various species in a conserved manner.

RNA secondary structure is a new regulatory layer of transcript fates. Here, Li et al. find that plant RNA helicase Brr2a, acting beyond its canonical role in spliceosome, can optimize secondary structure of pri-miRNAs to promote miRNA production.

The mechanism of action of LNA043—a novel disease-modifying osteoarthritis treatment candidate—is characterized in preclinical studies and through transcriptomic profiling of cartilage from patients with osteoarthritis in a phase 1 trial.

The authors study microbial communities in hydrothermally heated, subseafloor sediment layers. They find that microbial abundance and diversity decrease with sediment depth and temperature, and provide evidence for the existence of a specialized deep, hot biosphere.

There is an unmet need to improve the response to immune checkpoint blockade in patients with head and neck squamous cell carcinoma (HNSCC). Here the authors show that aberrant HER3 activation sustains the proliferation of PIK3CA wild type HNSCC cells and that HER3 inhibition increases response to PD-1 blockade in HNSCC preclinical models.

While the role of smooth muscle in peristalsis has been studied extensively, little is known about its other functions in the intestine. Here the authors identify MMP17, expressed by smooth muscle cells, as a modulator of intestinal epithelial regeneration and the intestinal stem cell niche.

The impact of SARS-CoV-2 infection in pregnancy remains underexplored. Here, the authors provide a comprehensive characterization of virus and immunological parameters in 31 SARS-CoV-2-infected pregnant women, finding evidence of vertical transmission in two of the mother-child pairs.

Chemical topology is important in bond-forming reactions, but understanding the relationship between them is challenging. Here, the authors report a study considering photo-induced cyclisations for a series of monodisperse macromolecules with defined spacers and apply their findings to 3D printing.

Here, the authors show that combining γ9δ2 TCR-mediated metabolic and co-stimulatory stress targeting by chimeric NKG2D or anti-CD277 co-receptors shapes transcriptomic heterogeneity of engineered T cells and is associated with improved control of solid tumors.

In February 2024, rapid, recurring X-ray bursts (quasi-periodic eruptions) were detected from the black hole within galaxy SDSS1335+0728. Named Ansky, the event features day-and-a-half-long flares and extreme energy levels, challenging existing models.

Post birth the gastrointestinal tract undergoes development including the establishment of the microbiome, establishment of tolerance and maturation of the epithelium. Here the authors show a histone demethylase LSD1 is required for postnatal intestinal epithelium maturation and how this impacts local immune cell composition and gut homeostasis.

A study reporting the results of a clinical trial co-administering the GDF-15-blocking antibody visugromab with the anti-PD-1 antibody nivolumab demonstrates that neutralizing GDF-15 can overcome resistance to immune checkpoint inhibition in cancer.

Genetic exchange of Leishmania parasites in the sand fly host is mediated by natural IgM antibodies, providing insights that will help generate reproducible and increased recovery of backcrosses for research purposes.

This study shows grey infrastructure (economy-linked) dominates flood control in normal rains. During extremes, its efficacy declines while green infrastructure/topography (less economy-aligned) become crucial for urban flood mitigation.

Durocher and colleagues identify CIP2A through synthetic lethal CRISPR screens as a key regulator of adaptive feedback mechanisms controlling chromosomal stability arising from accumulated DNA lesions in BRCA-mutated tumor cells.

Immunotherapy with immune checkpoint inhibitors and targeted therapy with BRAF and MEK inhibition have revolutionized the treatment of melanoma. Here the authors report the results of a phase II trial of neoadjuvant cobimetinib (MEK inhibitor) and atezolizumab (anti-PD-L1) with or without the BRAF inhibitor vemurafenib in patients with resectable Stage III melanoma.

Asian soybean rust caused by Phakopsora pachyrhizi is an important plant pathogen, but an accurate genome assembly for this fungus has been lacking. This study sequenced three independent P. pachyrhizi isolates and generated reference quality assemblies and genome annotations, representing a critical step for further in-depth studies of this pathogen and the development of new methods of control.

Down syndrome is the most common genetic form of intellectual disability. In this Review, Mara Dierssen examines the underlying mechanisms that give rise to brain dysfunction in Down syndrome and discusses therapeutic approaches that are under investigation to combat cognitive deficits associated with this condition.

The climate crisis will increase the frequency of extreme weather events. Harrison et al. show that while global waterlogging-induced yield losses increase from 3–11% historically to 10–20% by 2080, adapting sowing periods and adopting waterlogging-tolerant genotypes can negate such yield losses.

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.

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.

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.

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.