Volume 57 Issue 9, September 2025

Despite Africa’s vast genetic diversity, its populations are underrepresented in global genomic datasets. Here we describe the vision of the KidneyGenAfrica, a pan-African initiative launched to address this inequity, and call for more inclusive genomics research that recognizes Africa’s key role in genetic variation and potential to generate insights in chronic kidney disease.

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.

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.

We combined CRISPR activation of all 1,836 known human transcription factors with high-throughput Perturb-seq to recreate the diverse transcriptional states occupied by fibroblasts in vivo. Our study revealed regulators of key states and showed that inducing normal states can, in some cases, suppress those linked to disease.

This Perspective proposes a human rights-based governance framework for cross-border genomic data sharing, addressing limitations of data sovereignty approaches while balancing privacy, security and global research collaboration.

This Perspective proposes a checklist of six database design considerations, LISTEN: licensed, identified, supervised, transparent, enforced and non-exclusive, aimed at ensuring access and benefit-sharing principles in open science.

Understudied cereals offer untapped potential for food security, yet multiomic research substantially lags behind that of major cereals. This Perspective discusses these challenges and introduces a dedicated database to serve the community.

LDAK-KVIK is a mixed-model association method for genome-wide studies that optimizes computational performance and power. LDAK-KVIK can also perform gene-based tests and produces state-of-the-art polygenic scores.

SINGER is a method for creating ancestral recombination graphs to understand the genealogical history of genomes. The method has increased speed, and thus scalability, without sacrificing accuracy.

Comparison of electronic health record-based phenotype risk scores (PheRS) and polygenic scores (PGS) across 13 common diseases and three biobank-based studies indicates that PheRS and PGS may provide additive benefits for risk prediction.

Noncoding rare variant analyses using whole-genome sequencing data from the UK Biobank identify gene–trait associations for 42 blood cell traits but find that most signals are driven by linkage disequilibrium between common and rare variants.

Multiancestry fine-mapping of brain protein quantitative trait loci coupled with Mendelian randomization analyses identifies protein–trait pairs consistent with causal effects across neurological and psychiatric conditions.

This study explores the genomic and transcriptomic landscapes of triple-negative breast cancer in African American women. The authors show that the mutational profile is broadly similar to that observed in European and East Asian ancestry women while highlighting some interesting differences.

Lineage tracing in mice identifies a subpopulation of basal cells that express Tmprss2 and Nkx3 as the origin of ERG-driven prostate cancer. Upon expansion, these cells show an enrichment for STAT3 chromatin binding and elevated expression of KMT2A and DOT1L as dependencies for ERG oncogenicity.

Sequencing analysis of tamoxifen-associated uterine cancers and further in vivo analyses suggest that the drug tamoxifen can activate the PI3K pathway in the absence of oncogenic mutations.

This analysis of whole-genome sequencing data from 421 multiple myeloma samples elucidates the timing of key genomic events and shows associations between the timing of 1q gain and clinical outcome.

This study explores the relationship between telomere length and clonal hematopoiesis. Splicing factor and PPM1D gene mutations are more frequent in people with genetically predicted shorter telomere lengths, suggesting that these mutations protect against the consequences of telomere attrition.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

This multiomic study, including single-nucleus DNA methylation and chromatin conformation matched with single-nuclei RNA sequencing, provides insights into the epigenomic landscape of human subcutaneous adipose tissue.

This study investigates the dosage-sensitive effects of BRG1, a core SWI/SNF subunit, on chromatin binding, accessibility and transcriptional regulation by precisely controlling its protein level.

Chromosome-level genome assemblies of migratory and desert locusts, coupled with epigenomic profiling of migratory locusts, reveal chromatin dynamics underlying polyphenism and X-linked dosage compensation following autosomal gene translocation.

A genus-level super-pangenome of Avena comprising 35 high-quality genomes from 23 cultivated or wild oat species highlights the evolution of Avena and the landscape of structural variations related to abiotic stress resistance.

New concepts for comparing the genomes of 27 naturally inbred Arabidopsis thaliana accessions provide essential insights into obtaining a less biased view of whole-genome polymorphism.

This study implicates GSL5 inactivation in high, broad-spectrum resistance to the clubroot pathogen Plasmodiophora brassicae in Arabidopsis thaliana, Brassica napus, Brassica oleracea and Brassica rapa.

Pan-cistrome of the maize leaf under well-watered and drought conditions profiled by haplotype-specific MOA-seq highlights the relevance of transcription factor binding QTLs for understanding phenotypic diversity in maize.

CRISPR activation of 1,836 human transcription factors recapitulates fibroblast transcriptional states observed in vivo and identifies regulators that can revert inflammatory states.