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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.

Myeloid derived suppressor cells (MDSC) are associated with tumourigenesis and therapy response. Here, the authors show that beta 2-adrenergic receptor activation in MDSC leads to metabolic rewiring which regulates chemotherapy response in preclinical models of blood cancer.

This work presents active metasurfaces enabled by reversible metal electrodeposition with exceptional optical tunability, spanning from visible to near- and mid-infrared.

Fibrin drives inflammation and neuropathology in SARS-CoV-2 infection, and fibrin-targeting immunotherapy may represent a therapeutic intervention for patients with long COVID.

Studying changes in the metabolic properties of kidney cancer in patients reveals an increased need for mitochondrial metabolism as tumors metastasize from the kidney to distant organs.

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.

Early vertebrate genomes were shaped by multiple whole-genome duplication (WGD) events of debated timings. Here the authors’ reconstruction of ancestral genomes using the probabilistic macrosynteny model supports a WGD shared by all vertebrates and a gnathostome-specific WGD, and reveals evidence of a cyclostome-specific genome triplication.

Electrochemical pumps can effectively purify and compress hydrogen for subsequent use in energy and industrial applications but struggle with low hydrogen concentrations. Here the authors present an electrochemical pump based on an ion-pair membrane that can produce high-purity hydrogen from a 10% blend in methane.

To address an evidence gap for the efficacy of hypertension therapy using dual drug combinations in patients of South Asian origin, a randomized clinical trial conducted in India found that three types of dual drug combinations, each administered in a single pill, had similarly large effects on reducing blood pressure.

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.

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 ComFC protein is essential for natural transformation, a process that plays a major role in the spread of antibiotic resistance genes. Here the authors show that ComFC is a membrane-associated protein that participates in the transport of DNA through the cell membrane and the handling of the single-stranded DNA once delivered into the cytoplasm.

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.

The adenosine A2A receptor (A2AR) plays a crucial role in regulating inflammation and metabolism, yet the extent to which endogenous metabolites modulate its activity remains unclear. Here, the authors utilized the MIDAS platform to identify metabolites interacting with A2AR, revealing orthosteric and allosteric modulators.

In mice, sympathetic nerves associated with female mammary glands control the secretion of thermogenesis-controlling factors by epithelial cells in the adipocyte niche, revealing sex-specific differences in adipose thermogenesis.

Fessler and colleagues report that loss of the IFN-γ-induced GTPase IRGM1 results in autoinflammatory disease. Deficient IRGM1 activity led to defective lysosomal maturation and impaired mitophagy, prompting the release of cytosolic mtDNA and thereby activating the cGAS–STING pathway.

Identifying biomarkers associated with risk of severe COVID-19 disease could inform clinical management. Here, the authors identify a long noncoding RNA associated with severe disease using data from three European countries, and validate their finding in data from Canada.

Dural-associated lymphoid tissues are lymphoid structures around vascular hubs in the dura mater that sample antigens and rapidly support humoral immune responses after local pathogen challenge.

Tiled amplicon sequencing is an essential tool for tracking the spread and evolution of pathogens, including SARS-CoV-2, however existing methods for tiled amplicon design require slow and costly downstream manual optimization. Here the authors present Olivar, a first step towards fully automated, variant-aware design of tiled amplicons for pathogen genomes.

Drug target identification is a crucial step in drug development. Here, the authors introduce a Bayesian machine learning framework that integrates multiple data types to predict the targets of small molecules, enabling identification of a new set of microtubule inhibitors and the target of the anti-cancer molecule ONC201.

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.

The incorporation of nitrogen in steroidal glycoalkaloids is hypothesized to occur through a transamination reaction. Here, the authors show that GLYCOALKALOID METABOLISM12 appears to evolve from the canonical γ-aminobutyric acid transaminases and directs the biosynthesis of nitrogen-containing steroidal metabolites in Solanum plants.

Steroidal glycoalkaloids (SGAs) accumulate in Solanum, but their hydroxylating enzymes are unknown. Here, the authors report 2-OXOGLUTARATE DEPENDENT DIOXYGENASE enzymes that catalyze the committed hydroxylation steps in the biosynthesis of leptinine insecticidal compounds in wild potato or non-bitter SGAs in cultivated tomato.

Analyses of hippocampal AMPA receptor–auxiliary subunit complexes provide insights into the predominant assemblies and organization of the AMPA receptor, TARP-γ8 and CNIH2/SynDIG4 and explain the mechanism of inhibition of a clinically relevant, brain-region-specific allosteric inhibitor.

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.

During tomato fruit ripening, bitter and toxic steroidal glycoalkaloids (SGAs) are converted to nonbitter and less toxic forms, but proposed acylating enzyme in pathway remain unknown. Here, authors report BAHD-type acyltransferase that catalyze acylation step in biosynthesis of non-bitter SGAs in tomato.

A free-standing two-dimensional sheet composed solely of Mo atoms shows metallic character, with an electrical conductivity of ~940 S m⁻¹.

3D heterostructures offer properties that are inaccessible in bulk single-phase solids, but synthetic approaches are limited. The authors use mechanochemical reshuffling of binary precursors and subsequent annealing to design structurally aligned misfit heterostructures with well-defined atomic arrangements.

Based on the identification of CD4⁺ T cell clones specific for distinct epitopes in the SARS-CoV-2 proteins, Long and colleagues characterize how mutations in these epitopes lead to loss of recognition by the CD4⁺ T cells elicited by natural infection or vaccination.

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.

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.

RNA in non-human primate liver is efficiently edited using short stereopure oligonucleotides.

A metal–organic framework membrane based on fumarate and mesaconate linkers is shown to have a pore aperture shape that enables efficient and cost-effective removal of nitrogen and carbon dioxide from methane.

A proteomic risk score for cardiorespiratory fitness, comprising as few as 21 proteins, is dynamic with exercise training and helps predict the risk of mortality and a range of cardiovascular, metabolic and neurological conditions.

Durable clinical benefit observed in recurrent ovarian cancer patients treated with combination pembrolizumab, cyclophosphamide and bevacizumab are associated with increased T and B cell clusters, distinct microbial patterns, and altered metabolism.

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.

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.

The biosynthetic pathway of strychnine, brucine and diaboline is described, and the biosynthesis of these complex, pharmacologically active compounds has been successfully recapitulated in Nicotiana benthamiana from an upstream intermediate.

Measurements suggest that emissions from biomass burning drive the rapid growth of particles from nanoscale into sizes relevant for haze formation during the night in Delhi.

This study looks at the diurnal temperature fluctuations in Kolkata through a model that tests the influence of rooftop photovoltaic solar panels on urban surface energy budgets, near-surface meteorological fields, urban boundary layer dynamics and sea breeze circulations. It found that panels heat cities during the day (up to 1.5 °C) but cool them at night (up to 0.6 °C).

A framework combining combinatorial CRISPR knockout in breast, lung and oropharyngeal cancer in vitro models with public data identifies synthetic lethal interactions, such as perturbed KDM5C sensitizing cells to PARP7 inhibition.

Adenosine deaminases acting on RNA (ADARs) impact diverse cellular processes. Here the authors chart time-course RNA editing profiles in human organs from fetal to adult stages to shed light on the role of ADARs in cell-fate specification.

Pathological cardiac fibrosis is a hallmark of diseases leading to heart failure. Here, the authors used systems genetics to identify a pro-fibrotic gene network regulated by WWP2, a E3 ubiquitin ligase, which orchestrates the nucleocytoplasmic shuttling and transcriptional activity of SMAD2 in the diseased heart.

Centring structure-directing agents govern structure assembly to consistently obtain sodalite topology backbone, yielding more than 20 isoreticular zeolite-like metal–organic frameworks with tailored pore apertures and porosity.

Serine deficiency can increase small fibre neuropathy in wild-type mice and serine replacement in diabetic mice alleviates diabetic neuropathy, directly linking amino acid metabolism to peripheral nerve disorders.