Reviews & Analysis

Evading elimination by the immune system is a hallmark of cancer, but the exact timing and pathways of immune evasion are still to be explored. Colorectal cancers were found to engage a combination of epigenetic, genetic and microenvironmental mechanisms, and establish immune evasion prior to their outgrowth.

We have discovered recurrent, somatic mutations in mitochondrial ribosomal RNA genes across all tumor types assessed. In contrast with the established idea that the majority of mitochondrial DNA molecules must be mutated to cause an effect, a low allelic dosage of these mutations disrupted mitochondrial protein translation, altering cancer metabolism and transcription.

Dilated cardiomyopathy (DCM) is more prevalent among individuals of African descent, but a genetic basis for this increased risk has remained unclear. By integrating genomic and phenotypic data from multiple African ancestry cohorts, we identified a common, ancestry-specific nonsense variant in CD36 that increases DCM risk by impairing myocardial energetics. This variant explains one-fifth of the excess DCM burden observed in individuals of African descent.

This Perspective examines the challenges to equitable participation of migrants and immigrants in genetics research and proposes inclusive, community-driven approaches to advance scientific discovery and overcome health disparities.

The epigenetic underpinnings of memory are still poorly understood. A study provides a causal link between the epigenetic dynamics of a single genomic locus in engram cells and memory formation, achieved by the development of a reversible epigenetic editing tool.

Spatial transcriptomics enables the characterization of diverse cell types with increasing resolution while retaining the spatial context of complex tissues. A study combines single-cell and spatial ‘spot’-based transcriptome measurements to identify cell states in the developing human heart and define spatial relationships within cardiac niches.

The transcription factors responsible for initiating embryonic genome activation (EGA) in humans remain largely unknown. A study now characterizes the role of the maternal factor OTX2 in kickstarting human EGA.

We developed a molecular tool that enables the loading of cohesin complexes at defined genomic regions in live cells. Use of this tool reveals that cohesin loop extrusion results in reduced gene expression and H3K27ac of sites in the TACL domains, thereby influencing the epigenetic composition of chromatin and the activity of genes within them.

Cell-free DNA from non-invasive prenatal screening reflects the maternal and fetal genome and epigenome. This Review discusses its analysis for actionable pregnancy complication prediction beyond the common trisomies, transforming obstetric care.

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.

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.

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.

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.

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.

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.

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.

GSL5, a glucan synthase, acts as a suppressor of jasmonic acid-mediated immunity in cruciferous plants. Inactivation of GSL5 by genome editing confers high-level and broad-spectrum resistance to pathogens that cause clubroot disease in four cruciferous species.

Tamoxifen is an essential drug in breast cancer therapy. Unlike prevailing models of therapy-related tumorigenesis, tamoxifen acts by directly activating the PI3K pathway, bypassing the need for mutations in one of the most common driver genes in sporadic uterine cancer. These findings open avenues for investigating similar mechanisms in other drugs.