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Analyses of in vivo models, cell lines and patient-derived samples show that apolipoprotein B mRNA-editing catalytic subunit 3B (APOBEC3B) not only restrains lung tumor initiation but also that its upregulation is associated with resistance to targeted therapies. This study highlights the complex and context-dependent role of APOBEC3B in lung cancer.
Single-cell transcriptomes and single-cell chromatin accessibility profiles generated using EasySci provide a global view of aging and Alzheimer’s pathogenesis-associated cell population dynamics in human and mouse brains.
Analysis of single-nucleus RNA sequencing and single-nucleus assay for transposase-accessible chromatin with sequencing data derived from synovium of patients with rheumatoid arthritis identifies regions with dynamic accessibility that correlate with cell states. Dynamic peaks are more strongly enriched for autoimmune disease heritability.
A downsampling approach to assess causal variant fine-mapping, replication failure rate, finds that commonly used methods may be miscalibrated. Simulations suggest this is probably due to a nonsparse genetic architecture model misspecification. Incorporating infinitesimal effects in the SuSiE and FINEMAP frameworks improves performance.
Cross-ancestry genome-wide association meta-analyses identify new risk loci for peptic ulcer diseases and provide evidence that gastrointestinal cell differentiation and hormone regulation contribute to their etiology.
Population analysis of 516 wild and domesticated broomcorn millet genomes and a graph-based pangenome based on de novo assemblies of 32 representative accessions identify genomic variations associated with domestication traits.
Roulette enables the estimation of germline mutation rates at basepair resolution from humans. Genes encoding small nuclear RNA showed significant deviations from the mutation rate predicted by Roulette, highlighting RNA polymerase III (Pol III)-dependent transcription as a potent source of mutations in the human genome.
A multivariate framework for isoform-resolution transcriptome-wide association studies enables modeling of a greater number of genes, with the benefit of identifying isoform-specific associations with psychiatric traits not observed at the gene level.
Genome-wide analyses yield insights into the polygenic effects contributing to clinical heterogeneity in attention deficit hyperactivity disorder, advancing understanding of its genetic etiology and serving as a model for future studies in other complex disorders.
Multi-ancestry genome-wide association meta-analyses identify risk loci for cannabis use disorder. Genomic structural equation modeling and genetic correlation analyses show overlap with several other traits, including impulsivity and psychopathology.
Phenotype imputation increases the effective sample size of major depressive disorder cases in UK Biobank, enhancing study power and polygenic risk score (PRS) accuracy. A new pleiotropy metric enables assessment of PRS specificity and comparison among different PRS models.
In pancreatic duct adenocarcinoma, super-enhancer RNAs (seRNAs) have higher N6-methyladenosine (m6A) levels than in adjacent normal tissue due to upregulation of the METTL3 cofactor CFL1. Aberrant m6A seRNAs promote oncogene expression via the YTHDC2–MLL1 complex.
Circular extrachromosomal DNA in high-risk medulloblastoma contributes to tumor heterogeneity and associates with relapse and survival. Enhancer rewiring events involving known oncogenes are frequent events, affecting transcription and proliferation.
CRISPR activation/interference screens identify transcriptional regulators of human CD8+ T cells, including BATF3. BATF3 overexpression counteracts T cell exhaustion and enhances cancer immunotherapy in in vivo models.
JaBbA v1 pinpoints the ‘loose ends’ of large (>10-kb) unmapped structural variants in short-read DNA sequencing, suggesting that about 90% of cancer chromosomal alterations outside centromeres are resolvable with short reads and that long reads will primarily improve calling of smaller somatic variants.
A barcode-based approach applied to UK Biobank and an Icelandic cohort identifies drivers of clonal hematopoiesis (CH) and finds associations between CH and multiple diseases. Genome-wide association analyses identify 25 loci associated with CH susceptibility.
Chromosome-level genome assemblies of three Allium crops (onion, garlic and Welsh onion) and spatial RNA sequencing provide insights into Allium trait evolution and gene expression patterns during onion bulb formation.
Homozygous loss-of-function variants in phospholipase A/acyltransferase 3 (PLAAT3) underlie a new lipodystrophy syndrome. Functional studies link PLAAT3 loss with peroxisome proliferator-activated receptor gamma (PPARγ)-mediated defects in white adipose tissue differentiation and function.
Single-haplotype genome assemblies from five cat species shed light on the dynamics of structural variations during felid radiation and resolve sensory gene repertoires associated with adaptation and domestication.