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Rare cells are often biologically and clinically important, but their low abundance makes them challenging to study using single-cell transcriptomics. Here, the authors develop PURE-seq which integrates FACS and PIP-seq to directly sequence ultra-rare cells. It captures cells at 1 in 1,000,000 rarity, which the authors demonstrate by profiling circulating tumor cells and identifying Egr1 as a regulator of mouse hematopoietic stem cell aging.

How white matter develops along the length of major tracts in humans remains unknown. Here, the authors identify fundamental patterns of human white matter development along distinct axes that reflect brain organization.

Young individuals with a history of self-harm exhibit heightened electrodermal activity in response to neutral and stress-related stimuli, extending our understanding of the biophysiological factors for self-harm vulnerability.

MedHELM, an extensible evaluation framework including a new taxonomy for classifying medical tasks and a benchmark of many datasets across these categories, enables the evaluation of large language models on real-world clinical tasks.

Native state proteomics of PV interneurons revealed unique molecular features of high translational and metabolic activity, and enrichment of Alzheimer’s risk genes. Early amyloid pathology exerted unique effects on mitochondria, mTOR signaling and neurotransmission in PV neurons.

Insulin signaling plays a crucial role in coordinating skeletal development with whole‑body energy metabolism. Here, the authors use phosphoproteomics to show insulin-signaling rewiring in aged, insulin-resistant bone and identify defective phosphorylation of AFF4 as a key mechanism for regulating gene-specific transcriptional activation.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Here, the authors show that brain dynamics mature from childhood to adulthood with increased hierarchical propagation and reduced visual-somatomotor dynamics. Top-down hierarchical flow strengthens throughout this developmental period.

In the nucleus accumbens, acetylcholine boosts dopamine release to promote effortful behaviour.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Here they demonstrate a therapeutic intervention elevating levels of CYP450-derived lipids to control the expansion of intermediate monocytes in tissue and peripheral blood, presenting a first in class therapeutic approach for treating chronic inflammatory disease.

A hybrid extracellular matrix–hydrogel with tunable mechanical stiffness and biochemical composition of young or aged cardiac tissue is used to identify the specific contributions of extracellular matrix ligands and mechanics for fibroblast aging.

MK-7762 is a new oxazolidinone antitubercular agent that is structurally similar to linezolid, and demonstrated in vivo efficacy, lesion penetration and limited toxicity compared to linezolid, indicating it could be used in broad tuberculosis regimens.

Structural, genetic, functional and biochemical analyses of the complex flagellar motor of Campylobacter jejuni reveal structural adaptations with an ancient origin also found more widely across bacterial species, including elements exapted from the type IV pilus machinery.

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.

Studies using mouse models of lung adenocarcinoma identify an association between age, iron homeostasis and tumour initiation potential that involves NUPR1 and lipocalin-2.

Cardiovascular function declines with age. In this study, the authors show that the BAT-derived lipokine 12,13-diHOME preserves cardiac function in aged mice by attenuating pathological CaMKII activity.

Young adults face rising loneliness and mental health challenges. In a study of 5,192 undergraduates, Pei et al. find that perceiving peers as empathic is related to better well-being. Students, however, underestimate peers’ empathy. Two field experiments offered simple interventions that reduced this empathy perception gap and increased social behaviour and connection.

A completely solid-state, single-chip, microwave-frequency surface acoustic wave phonon laser can generate coherent phonons from thermal noise or resonantly amplify injected phonons using only a direct current bias field.

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.

Observations of ¹³CO in the atmosphere of a young, accreting super-Jupiter indicate a ¹³C-rich atmosphere, which is attributed to the accretion of carbon from ices enriched in ¹³C through fractionation.

Two eye-tracking experiments revealed that adolescents and older adults look less at social stimuli during a face-to-face conversation and while navigating the real world compared with young adults, which may affect the success of their social interactions.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Current vessel grafts must be surgically replaced when the recipient outgrows them. Here, Syedain et al.bioengineer a tube of acellular matrix produced from sheep fibroblasts that is capable of cellularizaton and somatic growth when transplanted into growing lambs, eliminating the need for multiple graft surgeries.

A clinical review of all pediatric deaths in England from March 2020 to February 2021 attributes 25 deaths to SARS-CoV-2 infection and identifies risk factors to guide interventions.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

Harmonizing data from 2390 participants across four diverse reaching studies, this work quantifies how age, sex/gender, and everyday experience influence reaction time, movement speed, and precision—establishing a robust normative benchmark for human motor control.

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.

Kraft, Murphy, Jones et al. identify extrachromosomal DNA (ecDNA)-interacting elements (EIEs) enriched for transposable elements within ecDNA in colorectal cancer cells. They show that EIE 14 integrated within ecDNA acts as an enhancer to promote cancer fitness.

The discovery of a vast reservoir of primordial neutral hydrogen gas surrounding a young galaxy cluster just one billion years after the Big Bang offers new insight into how the first large cosmic structures assembled.

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.

Activating oncogenic mutations in KRAS and NRAS are common in colorectal cancer, which is a heterogenous disease. Here, the authors show that the RAS mutation spectrum is markedly different between colon and rectal cancer, and also different based on age of diagnosis and microsatellite instability.

An exploratory analysis of the phase 3 ECOSPOR III trial shows that a higher dosage of the oral microbiome therapeutic VOWST led to enhanced pharmacokinetics, increased species engraftment and altered microbiome and metabolite profiles, providing mechanistic insights into how it may prevent Clostridioides difficile infection recurrence.

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.

Ischemic heart disease causes irreversible damage due to poor cardiomyocyte renewal. Here, the authors show that PKM2 modRNA therapy in pigs drives cardiomyocyte proliferation, minimizes fibrosis, restores cardiac function and prevents heart failure after injury.

H5N1 avian influenza viruses caused an outbreak in dairy cattle. We show that the potential for avian viruses to replicate in cow cells varies across H5N1 evolution, suggesting that the risk of spillover into mammals differs between variants.

Analysis of known viruses in stool samples from young children with high genetic risk for type 1 diabetes shows that sustained enterovirus B (EV-B) infections, rather than independent, short-duration EV-B infections, might be involved in the development of islet autoimmunity, but not type 1 diabetes.

Neurocognitive impairment and premature aging often occur in childhood survivors of cancer. Here, the authors investigate the link between biological markers of age and neurocognitive functioning in survivors of childhood cancer who received either central nervous system (CNS)-targeted or non-CNS-targeted therapy.

In a trial involving 45 clinics and 15,596 visits, the use of an AI-based screening tool applied to ECG for opportunistic detection of advanced chronic liver disease led to a significant increase in new diagnoses compared to the standard workflow.

The risk of intensive care unit admission among children with COVID-19 or its sequelae is affected by age, ethnicity and comorbidities. Understanding these modifiers might help identify at-risk children and guide interventions.

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.

Surgical menopause occurs in premenopausal women who undergo radical cystectomy with bilateral oophorectomy to treat bladder cancer. This Review discusses the pathophysiology of surgical menopause in these patients and highlights current strategies to mitigate associated symptoms and long-term health risks.

A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

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.

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

HIV vaccine development can be aided by knowledge of correlates of protection. Here the authors identify engagement and reprogramming of tolerogenic CD14⁺ myeloid cells mediating a spatiotemporal balance of pro- and anti-inflammatory responses, as correlates of efficacy in female macaques vaccinated with the DNA/ALVAC/gp120/Alum platform.

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.

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.