Volume 58 Issue 1, January 2026

Being an African scientist, I had to overcome several challenges to generate substantial data that shed light on the complexity of genomic medicine in African populations and abroad.

The BioDIGS project is a nationwide initiative involving students, researchers and educators across more than 40 research and teaching institutions. Participants lead sample collection, computational analysis and results interpretation to understand the relationships between the soil microbiome, environment and health.

Amid growing geopolitical tension and scientific advances, fragmented and reactive governance policies could increase the risks of dual-use genomics, undermining international collaboration and data security. This Comment calls on the international genomics community to meet to establish robust, harmonized standards to safeguard genomic data.

A study reveals how chromosomal instability and resultant TP53 loss enhance fatty acid metabolism to drive breast cancer brain metastasis. This metabolic dependency provides new insights into therapeutic vulnerabilities of aneuploid tumors.

Primary mismatch repair-deficient gliomas are hypermutant but molecularly heterogeneous cancers with poor prognosis. We show that non-random mutational signatures cause somatic mutations in key glioma drivers that define genetic subgroups of this disease. Each subgroup harbors distinct mechanisms of genomic instability that shape their biological behaviors and immunotherapy responses.

We developed DNA-Diffusion, a generative artificial intelligence (AI) method that creates synthetic regulatory elements showing enhanced activity. Multiple synthetic elements demonstrated superior cell-type-specific expression in computational predictions and episomal assays, and when integrated at AXIN2, a leukemia-protective gene, outperformed naturally occurring protective variants, opening new possibilities for precision gene therapies.

This Perspective provides a practical and clinically relevant framework rooted in benefit–risk analyses to evaluate genomic CRISPR off-targets. Such an approach is applicable to currently available as well as future technologies.

This Review discusses the high-impact variants in 12 small nuclear RNA genes that cause Mendelian disorders with either autosomal dominant or recessive inheritance patterns, highlighting the biochemical consequences and therapeutic implications.

This study uses a high-dimensional proteomics panel to explore protein-level genetic associations with type 2 diabetes in a Ugandan cohort.

Genome-wide association studies (GWAS) of deep learning-derived measurements of aortic valve function, along with multitrait analyses incorporating disease-based GWAS, identify 166 genetic loci associated with aortic valve function or aortic stenosis.

Multi-ancestry genome-wide and transcriptome-wide association studies of aortic stenosis identify more than 200 independent risk loci and provide insights into its genetic architecture.

MultiSuSiE is an extension of the Sum of Single Effects fine-mapping model that allows causal effect sizes to vary across ancestries. Applying MultiSuSiE to quantitative traits in All of Us identifies fine-mapped variants not implicated by other methods.

Protein quantitative trait loci show enrichment of trans effects among proteins in the same interaction networks and among missense variants at interaction interfaces, highlighting pathways impacted by trait-associated variants.

This paper introduces breakage–replication/fusion, a genomic rearrangement process underpinning three patterns of copy-number gains found in cancer and other diseases.

Npm1 promotes tumor formation via attenuating the integrated stress response and p53 activation in mouse WNT-driven intestinal and liver tumorigenesis.

This study associates p53 loss and brain metastasis in breast cancer. Mechanistically, p53-null tumors recruit astrocytes that provide substrates for enhanced fatty acid synthesis via upregulated SCD1 expression, representing a targetable axis in the disease.

The authors analyze 162 primary mismatch-repair-deficient gliomas and identify three subgroups underpinned by distinct somatic mutations in replicative DNA polymerases and IDH1.

DNA methylation and copy number variant analyses across a large number of genetic mouse models of pediatric brain tumors reveal subtype-specific molecular alterations shared with the corresponding human diseases.

Saturation mutagenesis screening examines 11,520 point mutations in the kinase domains of FGFR1, FGFR2, FGFR3 and FGFR4, identifying their activating and resistance properties to the FGFR inhibitors pemigatinib and futibatinib.

De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

The authors present DNA-Diffusion, a generative AI framework that designs synthetic regulatory elements with tunable cell-type specificity. Experimental validation demonstrates their ability to reactivate AXIN2 expression, a leukemia-protective gene, in its native genomic context.

A telomere-to-telomere gap-free pig genome assembly (T2T-pig1.0) for a Wuzhishan boar highlights Y chromosome structure and genomic regions potentially associated with body stature.

Natural variation in the promoter of OsTPS8 contributes to differences in grain chalkiness and seed vigor between indica and japonica rice subspecies by altering trehalose-6-phosphate biosynthesis and α-amylase levels.

Genome assemblies of 100 cultivated and seven semi-wild Gossypium hirsutum accessions provide insights into the evolutionary history of upland cotton and the genetic basis of fiber trait variation.