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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.

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.

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.

It remains a challenge to find the structure and the distribution of the constituents of nucleons. Here the authors use a scattering method to get information about the gluons and quarks inside a proton and separate the contribution of Bethe-Heitler from the deeply virtual Compton scattering process.

Discovery of a biochemical mechanism through which lactate binds and inhibits the SUMO protease SENP1, stimulating timed degradation of cell cycle proteins, and resulting in mitotic exit.

Insertion of a bivalent linker between two regions of interest allows chromatin contacts to be probed without proximity ligation.

The biosynthesis of membrane-spanning lipids in archaea is poorly understood. Here, Li et al. identify an archaeal enzyme that forms a C(sp³)–C(sp³) linkage between isoprenoid chains for the synthesis of membrane-spanning GMGT lipids, and show that the corresponding gene is exclusively found in obligate anaerobic archaea and in metagenomes from oxygen-deficient environments.

The selective CO₂ photoreduction in water mediated by earth-abundant photocatalysts remains highly challenging. Here the authors present the coordinative anchorage of molecular catalysts on a pyridine-armed covalent triazine framework for CO₂ photoreduction to CO in fully aqueous solutions.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

Genetic screening identifies a rich catalogue of regulators of micronucleus formation.

The neural mechanisms responsible for cold defense regulation are still unclear. Here, authors show parallel thermogenic pathways from the brain stem to the hypothalamus work together to enable resilience to cold temperature exposure and hypothermia.

Turbulence plays a key role in space and astrophysical plasmas. The study reports evidence of the weak-to-strong transition when Alfvénic turbulence cascades from large to small scales revealed from the Cluster observation of space plasma.

Most of the more than 200 known genetic risk loci for inflammatory bowel disease (IBD) reside in regulatory regions. Here, the authors provide eQTL datasets for six circulating immune cell types and ileal, colonic and rectal biopsies to map regulatory modules and identify potential causative genes for IBD.

The scarcity and high price of noble metal catalysts pose critical challenges for the chemical industry, and finding strategies that ensure complete atom efficiency has become a pivotal endeavour. This work introduces the fabrication of amorphous single-layer PtSe_x catalysts for the hydrogen evolution reaction with high atom-utilization efficiency.

The internal structure of the neutron has now been probed by highly energetic photons scattering off it. Combined with previous results for protons, these measurements reveal the contributions of quark flavours to the nucleon structure.

Defective neoangiogenesis and blood–brain barrier leakiness are pathological hallmarks of neuroinflammation. Here the authors show that vascular endothelial growth factor A (VEGF-A) promotes venous endothelial cell proliferation, resulting in the formation of leaky vessels around demyelinating lesions in multiple sclerosis and experimental autoimmune encephalomyelitis.

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.

Low effective doping of boron limits the performance of solar cells based on hydrogenated amorphous silicon. Liu et al. show that light induces the diffusion of hydrogen atoms, which activates boron doping, enabling a power conversion efficiency of over 25%.

Here the authors developed ‘Lamina-Inducible Methylation and Hi-C’ (LIMe-Hi-C) to simultaneously measure chromosome conformation, DNA methylation, and nuclear lamina positioning. Application of the method revealed dynamic changes upon PRC2 inhibition and an essential function of H3K27me3 in regulating sub-compartments and lamina association.

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.

Sensing DNA bases by surface-enhanced Raman spectroscopy (SERS) in plasmonic nanopores has suffered from rapid flow through of molecules. Here, the authors attach DNA molecules to gold nanoparticles which, due to electro-plasmonic trapping, allow for controlled residence times and discrimination of single nucleotides.

There is emerging interest in photodetectors in the mid-infrared driven by increasing need to monitor the environment for security and healthcare purposes. Sassiet al. show a thermal photodetector, based on the coupling between graphene and a pyroelectric crystal, which shows high temperature sensitivity.

Long-term stability is a key challenge for ruthenium-based oxygen evolution reaction (OER) catalysts. Here, the authors present a RuO2/LiCoO2 catalyst with dynamic Li dissolution, which weakens the covalency of the Ru-O bond to prevent the lattice oxygen mechanism, thereby ensuring stable acidic OER.

Variation in the IL-7 receptor is associated with susceptibility to multiple sclerosis. Jingwu Zhang and his colleagues provide an explanation. They show that the cytokine IL-7 regulates the surival and proliferation of T helper type 17 cells—a cell type known to be involved in the pathogenesis of multiple sclerosis. The findings suggest that IL-7 antagonism could be useful in individuals with autoimmune diseases such as multiple sclerosis (pages 166–168).

Structural variants (SVs) contribute to the genetic architecture of many brain-related disorders. Here, the authors integrate SV calls from genome sequencing (n = 755) with RNA-seq data (n = 629) from post-mortem dorsal lateral prefrontal cortex to annotate the gene regulatory effects of SVs in the human brain and their potential to contribute to disease.

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.

In semiconductor quantum dots, interactions between the confined electrons and the surrounding reservoir of nuclear spins limit the attainable electron-spin coherence. But the nuclear-spin reservoir can also take a constructive role, as it facilitates the locking of the optical quantum-dot resonance to the changing frequency of an external driving laser, as an experiment now demonstrates.

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.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

Form factors encode the structure of nucleons. Measurements from electron–positron annihilation at BESIII reveal an oscillating behaviour of the neutron electromagnetic form factor, and clarify a long-standing photon–nucleon interaction puzzle.

Electrons in uranium-based materials are often on the border between localised and itinerant behaviour, which can lead to unusual magnetic behaviour. Here the authors combine experiment and theory to show that USb₂ may be an unusually high temperature example of a singlet-ground-state magnet.

Triclosan (TCS), an antimicrobial agent commonly found in consumer products, has been reported to exacerbates colitis in animal models. Here, using in vitro and in vivo approaches, the authors show that gut bacterial enzymes can drive the metabolic activation and gut toxicity of TCS, highlighting an important role of intestinal microbial factors in the complex etiology of colitis.

The DNA modification N⁶-methyladenine regulates gene expression during mouse trophoblast development by depositing at the boundaries of active chromatin and preventing its spread by antagonizing the chromatin organizer SATB1.

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 ability to regulate nanobody affinity with light would expand the applications toolbox for these reagents. Here the authors insert an optimised photoswitchable AsLOV2 domain into multiple nanobodies and demonstrate photoswitchable binding to fluorescent proteins and endogenous proteins in cells.

Gene discovery and polygenic predictions from a genome-wide association study of educational attainment in 1.1 million individuals.

Macrophage-mediated immune suppression contributes to poor outcome in liver metastasis. Here the authors show that CD36-expressing metastasis associated macrophages engulf tumor cell-derived extracellular vesicles enriched in long-chain fatty acids, acquiring a pro-tumorigenic phenotype in a preclinical liver metastasis model.

The gluonic gravitational form factor of the proton was determined using various models, and these analyses showed that the mass radius of the proton was smaller than the electric charge radius.

The orphan enzyme phosphotriesterase-related (PTER) is identified as a mammalian N-acetyltaurine hydrolase that has roles in regulating body weight and energy balance.

Detecting Alzheimer’s disease from blood samples is challenging because amyloid β blood levels are lower than the ELISA detection limit. Here the authors capture amyloid β bound to circulating exosomes on a plasmonic nanosensor, followed by enzymatic amplification to improve detection sensitivity.

Bioresorbable electronic stimulators can deliver electrical stimulation in rodents to enhance functional muscle recovery after nerve injury. Here, the authors present a bioresorbable dynamic covalent polymer that enables reliable, long-lived operation of soft, stretchable devices of this type.

Antibodies (Abs) targeting highly conserved epitopes are important tools against emerging virus variants. Here, the authors characterize Abs that recognize a cryptic epitope in the receptor-binding domain of SARS-CoV-2 spike that is well conserved and show that these Abs can neutralize several variants of concerns.

A technique using barcoded beads for DNA sequencing within tissue sections enables spatial resolution of tumour clonal heterogeneity and can be multiplexed with other analytical techniques for analysis of complex cellular phenotypes.

A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.

Optogenetically controlling the assembly of enzyme clusters enhances product formation and specificity during deoxyviolacein biosynthesis by decreasing concentrations of intermediate metabolites and reducing flux through competing pathways.