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A large cross-population atlas of gene–environment interactions reveals how age, sex and lifestyle shape genetic effects, heritability, prediction accuracy and disease biology, with implications for personalized medicine and drug development.

A Stereo-seq and scRNA-seq atlas of mouse liver in homeostasis and regeneration after partial hepatectomy identifies zonated genes, pathways, cell–cell interactions and gene regulatory networks. Functional validation finds that cooperation between TBL1XR1 and β-catenin activates hepatocyte proliferation.

A comprehensive multi-omics reference atlas of prenatal human skin shows that innate immune cells crosstalk with non-immune cells to perform pivotal roles in skin morphogenesis, including the formation of hair follicles.

Using infant fMRI, the authors show that, by 2 months of age, representations in high-level visual cortex encode visual categories that align with deep neural networks, and lateral object-selective regions are later to develop.

Here, using human liver chimeric mice, the authors describe perturbation of the diurnal transcriptome and epigenome of human hepatocytes during hepatitis C virus infection, affecting pathways mediating metabolic alterations, fibrosis, and cancer, and further show that the pathways remain affected in patients with advanced liver disease.

Nicole Soranzo, Tim Spector, Gabi Kastenmüller and colleagues report a large-scale analysis of genetic variants influencing human blood metabolite levels. They identify genome-wide significant associations at 145 loci, providing a framework for exploring relationships between genetic variation, metabolism and complex disease.

A multi-modal analysis of pre-metastatic liver biopsies from patients with localized pancreatic cancer with a minimum of 3 years of follow-up shows that immunological, proliferative and metabolomic features distinguish patients who develop metastases from disease-free survivors and can be used to predict outcomes.

An atlas of Bacillus subtilis transcription terminators reveals Rho-stimulated intrinsic termination.

Here the authors provide the biospecimen collection methodology from the SpaceX Inspiration4 mission, including venous blood, capillary blood, saliva, urine, stool, skin biopsy, body swab, and environmental swab samples.

Elevated type 2 functionality in CAR T cell infusion products is significantly associated with maintenance of a median B cell aplasia duration of 8.4 years in paediatric patients with acute lymphocytic leukaemia.

Single-cell profiling studies of the human gastrointestinal tract are increasing, offering an excellent opportunity to generate the first Human Gut Cell Atlas. This Roadmap presents a structured direction towards this goal and provides a detailed overview of the major challenges.

The substantia nigra is important in neurological disease, particularly movement disorders. Here the authors provide a single cell transcriptomic atlas for the human substantia nigra.

Studying Drosophila trachea development can inform the mechanisms of growth of all tubular structures. Here, the authors generate a transcriptomic cell atlas of the developing fly trachea and establish roles for Notch signaling, which may be disrupted by diet-induced glycosylation.

A comprehensive spatial expression atlas of the adult human proximal small intestine reveals branched villi, immune activation at the villus tip, and a switch of migrating enterocytes from lipid droplet assembly and iron uptake at the villus bottom to chylomicron biosynthesis and iron release at the tip.

Recent phylogenetic analyses have identified orphan clades, including Xenacoelomorphs, that can offer insights into bilaterian evolution. Here they generate a cell type atlas of Xenoturbella bockithat highlights cellular diversity in the nervous system and other tissues, reinforcing the idea of parallel evolution of cell types across animals.

Alatrakchi and colleagues profile immune cells from liver and blood obtained from patients with MASLD/MASH using single-cell sequencing. They note increased immunoregulatory programs that correlated with increased fibrogenesis and disease progression.

Sydnor et al. developed a new tractography atlas of thalamocortical structural connections and applied it to three youth samples. They uncovered coordinated development between thalamic connectivity and hierarchical cortical plasticity in humans.

Lifestyle interventions are promising tools for achieving healthy aging. Here, authors show how environmental enrichment can reverse multi-omic alterations associated with the aging process in the murine dorsal hippocampus.

A machine learning approach is used to analyse multi-omics (proteomics, metabolomics and transcriptomics) data, producing genetic scores for more than 17,000 biomolecular traits in human blood, and identifying possible associations with disease.

It remains unclear how cortical high-frequency oscillations (HFOs) and their relation with slow waves change with age. Here, the authors found that while HFO rate widely decreases over time, its coupling with slow waves strengthens in the occipital lobe during childhood.

An active atlas for automatic alignment of brains to a reference atlas is presented. The method uses the fine-scale pattern of tissue. The atlas is refined by each new brain and can inform on the structural variability between different brains.

Collision cross section (CCS) information can aid the annotation of unknown metabolites. Here, the authors optimize the machine-learning based prediction of metabolite CCS values and curate a 1.6 million compound CCS atlas, improving annotation accuracy and coverage for known and unknown metabolites.

PCNA–PAF15 has a key role in determining replisome dynamics during genome replication and protecting against genome instability.

The human skin is a highly complex organ comprising multiple tissue layers and diverse cell types. Here, the authors present a spatially-resolved quantitative proteomic atlas of the healthy human skin, characterizing the protein profiles of four skin layers and nine cell types.

Using 3D numerical models, this research shows how pre-existing rift basin structures influence the shape and growth of mountain belts, offering a way to link surface topography with deep Earth processes in regions like the Pyrenees and Caucasus.

The Human Endometrial Cell Atlas integrates single-cell transcriptomic datasets from women with and without endometriosis. Novel and known cell types are registered using spatial transcriptomics to provide a comprehensive map of the human endometrium in controls and endometriosis cases.

The ATLAS experiment at the Large Hadron Collider reports a search for charged-lepton-flavour violation in decays of Z bosons into a τ lepton and an electron or muon of opposite charge.

Multi-omics profiling of 45 human lung samples highlights 80 different cell types along the proximal to distal axis of the lung with certain cell types showing enrichment for disease-associated genes. An immune niche for IgA-expressing plasma cells within airway submucosal glands (SMG) is also identified.

Here the authors leverage state-of-the-art quantitative proteomics to provide a comprehensive overview of the human citrullinome. Supporting evidence from peptide microarrays hints at the potential clinical relevance of some of the identified sites.

The ATLAS Collaboration reports a measurement of the ratio of the decay rates of W bosons to τ leptons and muons, in agreement with universal lepton couplings as postulated in the standard model of particle physics.

This Roadmap presents and outlines the creation of the Human Liver Cell Atlas as a reference map and resource for the liver community, providing an overview of the steps needed to build the atlas, as well as outlining the major challenges and potential of this venture.

The number of single-cell RNA-seq datasets generated is increasing rapidly, making methods that map cell types to well-curated references increasingly important. Here, the authors propose an accurate method for mapping single cells onto a reference atlas in seconds.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Loss of inner ear hair cells leads to permanent hearing loss and balance dysfunction. Whether human utricular cells regenerate is unknown. Here, the authors present a single-cell resource of utricular cells from organ donors and schwannoma patients and describe transcriptional changes during homeostasis and in response to damage.

Adjuvants provide additional impetus for the immune response to vaccination regimens, however their modes of activity and impact on particular compartments of the immune response are currently not well understood. Here the authors perform high resolution assessment of the immune response to a well-established vaccination model and show innate immune transcriptomic and epigenomic alterations of innate cells in the lymph nodes following vaccination.

Drug synergies impact the efficacy of combination therapies but are difficult to identify. Here Narayan et al. describe the drug atlas, a method to predict effective drug combinations from common exclusive drug effects providing a resource for exploring and understanding effective drug combinations.

The measurement of the total cross-section of proton–proton collisions is of fundamental importance for particle physics. Here, the first measurement of the inelastic cross-section is presented for proton–proton collisions at an energy of 7 teraelectronvolts using the ATLAS detector at the Large Hadron Collider.

An integrated data and sample repository for clinical, cellular and multi-omics research from diverse spaceflight missions known as Space Omics and Medical Atlas (SOMA) is presented.

Comparing single-cell RNA-seq and ATAC-seq data from multiple batches is challenging due to technical artifacts. Here, the authors propose a method that disentangles technical and biological effects, facilitating batch-confounded chromatin and gene expression state discovery and enhancing the analysis of perturbation effects on cell populations.

Genome-wide association studies comprising 1,091 metabolites and 309 metabolite ratios in 8,299 individuals from the Canadian Longitudinal Study on Aging provide insights into the genetic architecture of metabolites and their role in human diseases.

A single-cell epigenomic atlas of human immune cells highlights cell-type-specific features associated with genetic or environmental exposures.

Analyses of single epithelial cells from early-stage lung adenocarcinoma and normal lung identifies a population of intermediate cells that may have an increased likelihood of transforming to tumour cells after injury such as tobacco exposure.

Using single-cell and spatial transcriptomics, human embryonic limb development across space and time and the diversification and cross-species conservation of cells are demonstrated.

Ten years after the discovery of the Higgs boson, the ATLAS  experiment at CERN probes its kinematic properties with a significantly larger dataset from 2015–2018 and provides further insights on its interaction with other known particles.

Single-cell transcriptomics of human lung tissue from individuals with tuberculosis identifies signatures of inflammation, apoptosis and senescence affecting immune, epithelial and endothelial cells linked with long-term pulmonary impairment.

Genome-wide analyses identify 43 loci associated with forearm fracture, including some influencing bone quality parameters. Follow-up work shows that Tac4 knockout mice exhibit reduced mechanical bone strength with no effect on bone mineral density.

pH is a critical regulator of (bio)chemical processes and therefore tightly regulated in nature. Now, proteins have been shown to possess the functionality to drive pH gradients without requiring energy input or membrane enclosure but through condensation. Protein condensates can drive unique pH gradients that modulate biochemical activity in both living and artificial systems.

N⁶-methyladenosine (m6A) and N⁶,2′-O-dimethyladenosine (m6Am) are eukaryotic mRNA modifications. Here the authors develop m6A-Crosslinking-Exonuclease-sequencing to map quantitative methylome changes at single-base-resolution after individually knocking out each known methyltransferase or demethylase.