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González-Gualda, Reinius et al. demonstrate that platinum-based chemotherapy-induced senescence promotes malignancy in ovarian and lung cancer via TGFβ ligands, with evidence in mouse models validated in clinical samples. Concomitantly blocking TGFβ signaling with chemotherapy reduces tumor burden and increases survival in mice.

This study reveals that the ability to maintain a stable body weight predicts longevity in mice. By tracking weight dynamics throughout life, the authors identify genetic loci linked to body weight, energy homeostasis and healthy aging.

In the adrenal cortex, cholesterol used for steroid production is stored in lipid droplets. The authors demonstrate here the importance of the transcription factor HHEX in maintaining glucocorticoid levels and protecting lipid droplets from androgen-induced lipid depletion.

The high-plasticity cell state (HPCS) is a critical hub that enables reciprocal transitions between cancer cell states, and targeting the HPCS may suppress cancer progression and eradicate treatment resistance.

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.

A forward genetic screen in Caenorhabditis elegans reveals that decreased levels of the ferredoxin FDX2 suppress the loss of frataxin in worms and in mice by relief of FDX2 inhibition of frataxin-stimulated NFS1 activity.

Neural crest cells have been implicated in heart development, yet the mechanisms by which they act have remained elusive. Here, the authors show neural crest cells modulate Wnt signalling in cardiac progenitors, providing new insight into the mechanisms underpinning congenital heart defects.

The cell states and lineage connections underlying the progression from Barrett’s esophagus to esophageal adenocarcinoma remain unresolved. Here, the authors use single-cell lineage tracing and transcriptomics to analyse patient samples from the gastroesophageal junction and identify cellular relationships in the progression of Barrett’s esophagus to cancer.

In this Review, Rowles and Patti present metabolomics workflows to study cancer across scales. They explore the nutrient demands of cancer cells and how those needs can be fulfilled through metabolic interactions within the tumour microenvironment or systemic crosstalk with distant tissues, and discuss the opportunities and challenges of each approach and offer insights into future research directions.

Roles of of viruses in ocean subsurface oxygen maxima are unclear. Here, the authors analyse Bermuda Atlantic Time Series data to show that viruses may drive SOM in stratified oceans by boosting nutrient recycling and phytoplankton productivity linking virus activity to oxygen buildup and a stronger microbial loop.

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.

A connectome of the right optic lobe from a male fruitfly is presented together with an extensive collection of genetic drivers matched to a comprehensive neuron-type catalogue.

ALMA has captured exquisitely detailed images of bowshock shells in the outflow of an outbursting protostar. These provide important insights into the variable nature of the ejections from protostars, which play a key role in star and planet formation.

Rajshekar et al. show that a hierarchy of affinities layers pericentromeric heterochromatin around nucleoli, with the RNA helicase Pitchoune (DDX18) acting as a key dual-affinity linker in Drosophila melanogaster.

Computer vision coupled with gene expression shed light on the collective organizational patterning of glioma stem cells, which correlates with glioma stem cell phenotypes

Genomic and phenomic screens of 827 wheat landraces from the A. E. Watkins collection provide insight into the wheat population genetic background, unlocking many agronomic traits and revealing haplotypes that could potentially be used to improve modern wheat cultivars.

Single-cell RNA sequencing maps tissue-level gene expression heterogeneity but faces challenges in interpreting biological signals due to noise and technical confounders. Here, the authors present sciRED, a method that enhances the interpretation of scRNA-seq factorization by linking factors to known covariates and hidden biological phenomena.

A software tool, EPIC, is developed to determine protein complex membership using chromatographic fractionation–mass spectrometry data, and is applied to map the global Caenorhabditis elegans interactome.

A pangenome analysis of 76 wild and domesticated barley accessions in combination with short-read sequence data of 1,315 barley genotypes indicates that allelic diversity at structurally complex loci may have helped crop plants to adapt to agricultural ecosystems.

Parkinson’s disease (PD) involves toxic protein buildup and energy failure in neurons. Continuously breathing low-oxygen air protected mice from PD-like neuronal loss and reversed symptoms, even after they began, suggesting that hypoxia may protect neurons.

The understudied lipid kinase PIP4K2C binds SARS-CoV-2 nonstructural protein 6 and regulates virus-induced autophagic flux impairment, suppressing viral protein degradation. PIP4K2C inhibition is a candidate strategy to combat emerging viruses.

Insufficient AHR activation has been suggested in SLE, and augmenting AHR activation therapeutically may prevent CXCL13⁺ T_PH/T_FH differentiation and the subsequent recruitment of B cells and formation of lymphoid aggregates in inflamed tissues.

Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

Lipoprotein uptake dependent on sulfated glycosaminoglycans linked to cell-surface proteoglycans is a key determinant of ferroptosis sensitivity in cancer.

The authors highlight inconsistencies and divergencies in the literature reporting data on indirect calorimetry for studies on whole-body energy homeostasis, and propose harmonization of standards to facilitate data comparison and interpretation across different datasets.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Tetrandrine is one of the most potent inhibitors of Ebola Virus infection. Here the authors identify LIMP-2 as a direct cellular target of Tetrandrine and establish a functional connection between lysosomal sphingosine homeostasis and calcium regulation.

The transcription factor CREM is a pivotal regulator of NK cell function, making CREM a valuable target to increase the efficacy of anticancer immunotherapies based on this cell population and chimeric antigen receptors.

Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.

Fibroblasts play critical roles in tissue homeostasis, but in pathologic states they can drive fibrosis, inflammation, and tissue destruction. Here, Faust et al. find that healthy human synovial fibroblasts under the influence of adjacent adipocytes have altered lipid metabolism driven by cortisol signaling. Both adipocytes and these characteristics are lost in inflammatory arthritis.

Olfactory neuroblastoma (ONB) is a rare malignant tumor whose genetic basis is poorly understood. Here the authors identify recurrent deletions involving dystrophin in the majority of ONB patient tumors examined.

Humans are exposed to millions of chemicals but mass spectrometry (MS)-based targeted biomonitoring assays are usually limited to a few hundred known hazards. Here, the authors develop a workflow for MS-based untargeted exposome profiling of known and unidentified environmental chemicals.

Genotype patterns may modify diet effects on weight loss, with greater weight loss on genotype-concordant diets. Here, the authors show that with the current ability to genotype participants as fat- or carbohydrate-responders, evidence does not support greater weight loss on genotype-concordant diets.

In this randomized crossover pilot study, the authors collected human gastrointestinal digesta using a unique intubation technique to compare how meals with contrasting cellular structures affect postprandial luminal metabolites, glycaemia, gut hormones and satiety sensation.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

Systems genetics reveals interactions between host and microbial phenotypes in the murine gut, including a role for Akkermansia muciniphila in the production of immunomodulatory ornithine lipids.

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.

A high-throughput screen of substances generally recognized as safe identifies species-specific materials that stabilize live microbial therapeutics as powders, making them robust to pharmaceutical manufacturing workflows.

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

Ribonucleoside monophosphates are incorporated by DNA polymerases into double-stranded DNA. Here, the authors use ribose-seq and Ribose-Map techniques to reveal that signatures and patterns of ribonucleotide incorporation in yeast mitochondrial and nuclear DNA show preference for cytosine and guanosine preceded by deoxyadenosine.

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.

Lim et al. identify CD34 as a surface marker of the heart’s sinoatrial node pacemaker cells, enabling their isolation from stem cell differentiation cultures, advancing future disease modeling, drug discovery, and biological pacemaker applications.

Data-driven detection of governing rules and trends in dynamics of nonautonomous systems usually requires a significant amount of measured data. The authors propose an operator-theoretic technique for identifying trends and persistent cycles using data from a single measured trajectory, relevant for the analysis of climate dynamics.

Cabozantinib, an inhibitor of multiple receptor tyrosine kinases, has efficacy in a mouse model of neurofibromatosis type I and has clinical activity in reducing plexiform neurofibroma volume in a phase II trial of patients with NF1.

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.

Protein-mediated transport is implicated in trafficking fatty acids at contact sites of lipid droplets and mitochondria. Here, the authors use proteomics to catalogue the proteins at this contact site and report a mechanism of fatty acid transfer that regulates fatty acid oxidation and lipid homeostasis.

This study demonstrates that the MKK3b/6 signalling pathway drives the skeletal muscle growth-promoting effects of resistance exercise.

This study codes about 500 pages from three urban development plans for the Greater Sydney area between 1968 and 2018 using causal maps. It found that there were unintended social and environmental consequences from the sustained economic growth strategy in the plans, and although there were attempts to solve them, there were never plans to change the dominant growth strategy.