Volume 57 Issue 10, October 2025

Using integrated single-cell multi-omics and spatial analysis, this study identifies a PRRX1-driven GPR116⁺ pericyte subpopulation that promotes tumor metastasis and immune evasion in esophageal squamous cell carcinoma, offering a diagnostic biomarker and potential therapeutic strategies.

Human centromeres contain a small chromatin region with low levels of DNA cytosine methylation that resides with CENP-A. Salinas-Luypaert et al. find a role of DNA methylation in maintaining the size and function of centromeres by controlling the binding affinity of key centromere components.

Bryophytes are a widespread group of land plants that occupy nearly all biomes, yet their genetics and evolutionary history have long remained underexplored. Now, a study that generates extensive genomic data for bryophytes highlights de novo gene formation and horizontal gene transfer as key forces that shape bryophyte diversity and adaptation.

In this study, we uncover the critical role of p300/CBP-mediated histone H2B N terminus multisite lysine acetylation (H2BNTac) in defining oncogenic enhanceosomes in prostate cancer. Degradation of p300/CBP rapidly disables H2BNTac-marked oncogenic enhancers and represents a promising therapeutic strategy for enhancer-driven malignancies, including prostate cancer.

We used a massively parallel reporter assay (MPRA) to test thousands of autoimmune disease-associated genetic variants for allele-specific effects on gene expression in primary human T cells. Variants that altered gene expression within our MPRA were then linked to T cell regulatory networks and proliferation using bulk and single-cell CRISPR-interference screens.

This Perspective presents the Solve-RD Solvathon model, an innovative, pan-European framework uniting clinical and bioinformatics experts to diagnose rare diseases through integrative multiomics analysis and structured collaboration.

The field of blood proteomics faces an upsurge of data with the challenge of cross-study comparisons. This Perspective offers an in-depth analysis and proposes reference materials to enhance data integration and accelerate clinical translation.

This Review discusses multiomic approaches for the characterization and biological understanding of cellular senescence, including detailed case studies on skeletal muscle and adipose tissue that highlight current outstanding issues in the field.

This Review discusses noncanonical DNA methylation (mCH) in animal genomes and highlights the remaining need to clarify whether mCH represents a conserved regulatory layer or a lineage-specific epigenetic feature with distinct biological roles.

Genome-wide analyses for 7,266 traits leveraging data from several genetic ancestry groups in UK Biobank identify new associations and enhance resources for interpreting risk variants across diverse populations.

Systematic comparison of genome-wide association results for disease risk and disease-specific mortality for nine common diseases across seven biobanks finds limited overlap between genetic effects on disease susceptibility and survival.

Genome-wide association meta-analyses of attention-deficit/hyperactivity disorder symptom measures and clinical diagnoses identify new risk loci, highlight putative effector genes and yield improved polygenic risk scores.

Analyses of whole-genome sequencing data from UK Biobank and All of Us identify rare variant burden signals associated with metabolic health, including effects of protein-truncating variants in IRS2 on type 2 diabetes and chronic kidney disease risk.

Genome-wide association analyses of 249 circulating small molecules and lipoprotein characteristics across the allele frequency spectrum in UK Biobank advance understanding of genes and pathways regulating human metabolism.

The authors present a molecular classification of acute leukemia using 5-methylcytosine signatures, together with a neural network-based classifier for clinical use.

This study shows that p300/CBP-dependent H2B acetylation is crucial for maintaining transcription of oncogenic gene programs in androgen receptor-driven prostate cancer.

This study uses spatial proteomic and spatial compartment-based whole-transcriptome profiling to develop predictive models for immunotherapy outcomes in non-small cell lung cancer.

This study provides a single-cell and spatial atlas of the prometastatic tumor microenvironment in esophageal squamous cell carcinoma and characterizes the immunosuppressive function of GPR116⁺ pericytes in cancer metastasis and immune evasion.

Genome-wide and targeted perturbation of DNA methylation at centromeres affects CENP-A positioning and centromere structure, resulting in aneuploidy and reduced cell viability.

This study introduces single-cell transcription factor (TF) sequencing, a single-cell barcoded and doxycycline-inducible TF overexpression approach that reveals dose-sensitive functional classes of TFs and cellular heterogeneity by mapping TF dose-dependent transcriptomic changes during the reprogramming of mouse embryonic multipotent stromal cells.

Massively parallel reporter assay in primary human CD4⁺ T cells and bulk and single-cell CRISPR-interference screens identify candidate causal variants linked to autoimmune disease risk that modulate T cell gene expression and proliferation.

This study introduces the Cattle Cell Atlas, a single-cell expression resource including 1,793,854 cells from 59 tissues. Integrative analyses leveraging this atlas provide insights into the biology underlying bovine monogenic and complex traits.

A super-pangenome analysis incorporating 123 newly sequenced bryophyte genomes reveals that bryophytes exhibit a larger number of unique and lineage-specific gene families than vascular plants.

Population history learning by averaging sampled histories is a new Bayesian method for estimating historical effective population size from recombining sequence data that offers improved speed and accuracy and enables uncertainty quantification and testing for ancient bottlenecks.

RNAtracker is a computational pipeline that distinguishes variants associated with allele-specific RNA stability from those associated with allele-specific RNA transcription. Variants affecting RNA stability are enriched in immune-related genes and contribute to disease risk.

Mapping pairwise nucleotide dependencies by leveraging genomic language models highlights functional genomic elements and predicts deleterious genetic variants more effectively than alignment-based conservation metrics.