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Here, the authors perform large trans-ancestry fine-mapping analyses identifying large numbers of association signals and putative target genes for colorectal cancer risk, advancing our understanding of the genetic and biological basis of this cancer.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

The basic features of dopamine release sites are still largely unknown. Here, the authors determine the ultrastructure of fluorescent dopaminergic and glutamatergic synaptosomes in mouse striatum using cryo-correlative light and electron microscopy.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

The authors present the results of a phase I/II clinical trial using autologous CD133+ bone marrow stem cell therapy to restore fertility in patients with Asherman Syndrome. The intervention was safe and showed promising results for the restoration of menstruation and reproductive function.

DNA interstrand crosslinks induced by acetaldehyde are repaired by both the Fanconi anaemia pathway and by a second, excision-independent repair mechanism.

Hepatocyte organoids derived directly from human tissue enable long-term hepatocyte expansion and can be combined with portal mesenchyme and cholangiocyte organoids to form a donor-specific periportal liver assembloid system.

Zhang et al. unveil that asymmetrically-dividing neural stem cells (NSCs) differentially propagate cell fate memory to future NSCs versus differentiating progenitors through a dual mitotic bookmarking and selective molecular competition mechanism.

A complementary analysis of DESI DR2 distance measurements along with supernova and CMB data shows consistent, moderate evidence that dark energy changes over time rather than behaving as a simple cosmological constant.

Analyses of consummatory reproductive behaviours in male mice uncover a brain mechanism whereby an internal state can attribute a social quality to a generic touch to initiate purposeful reproductive actions.

Here, the authors report an exome-wide association study for multi-organ imaging traits by leveraging recent bioinformatic tools such as AlphaMissense. The identified signals elucidate the genetic effects from rare variants on human organs and their connections to complex diseases

In correlated materials, new phases emerge when the balance between many-body interactions is perturbed. Here, Ma et al. induce a mosaic charge-density-wave phase out of Mott insulating state in layered 1T-TaS₂by voltage pulses, which reveals a dominating role of interlayer stacking order.

Single cell transcriptomics and chromatin accessibility uncover the gene networks underlying planarian cell type differentiation, revealing insights into the combinatorial logic of planarian cell fate specification.

Gaggioli, Lo et al. show that the histone methyltransferase EHMT2/G9a catalyses heterochromatin assembly at stressed replication forks. Untimely heterochromatin disassembly by demethylase KDM3A exposes forks to PRIMPOL-mediated genome instability.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Chromatin structure is thought to regulate transcription factor access by modulating DNA accessibility. Here, the authors show that in living human cells, euchromatin and heterochromatin are fully accessible, while centromeric chromatin remains partially inaccessible.

White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.

During the Last Ice Age, Neanderthals used a small cave in the Iberian Peninsula to accumulate the crania of large ungulates (bison, aurochs, red deer and rhinoceroses), some associated with small hearths. This seems to have been a symbolic practice.

An organoid system comprising adult mouse hepatocytes, cholangiocytes and mesenchymal cells recapitulates liver morphology, biliary function and fibrotic pathology, providing a new model for studies of hepatic biology.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

This pilot trial showed that perioperative treatment with the isocitrate dehydrogenase (IDH) inhibitor safusidenib of patients with low-grade IDH-mutant glioma, with craniotomy and lumbar puncture before and after treatment, is feasible and safe and enabled in-depth translational investigation of safusidenib treatment-induced changes in the tumor, including electrophysiological effects.

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.

Somatic cell reprogramming can induce distinct pluripotent states. Here the authors perform time-resolved whole-genome bisulfite sequencing during the reprogramming of mouse embryonic fibroblasts and report dynamic global DNA methylation changes.

Proteomics must target specific synapse types to reveal how molecules shape their unique functions. Here, authors show that hippocampal synapses differ in proteome and that neuron-specific glutamate receptor regulation shapes synaptic diversity.

Cardiac fibrosis arises from persistent myofibroblast activity. This study reveals how chromatin factors control scar-forming cells in the heart and shows that inhibiting KAT5 can reduce harmful cardiac fibrosis.

Comparative epigenomics has revealed principles underlying the evolution of gene expression regulation, and the integration of epigenomic data is important for a deeper understanding of this evolution. Here the authors report the evolutionary dynamics of the epigenomic regulatory landscape in primates and their impact in recent human evolution.

Understanding principles that govern protein association with extracellular vesicles should expand their potential as a therapeutic modality. Here, the authors show that by localizing proteins to the plasma membrane and lipid rafts, a variety of proteins can be preferentially loaded into extracellular vesicles.

Multiancestry genome-wide association analyses identify new risk loci for stroke and stroke subtypes. Fine mapping and bioinformatics analyses of these risk loci point to mechanisms not previously implicated in stroke pathophysiology.

Together with a companion paper, molecular details of immune responses in a pig-to-human xenotransplantation are identified through dense longitudinal multi-omics profiling of the xenograft and the host recipient, across the 61-day procedure.

Introduction of structured neutron waves carrying orbital angular momentum (OAM) in small-angle neutron scattering experiments provides novel approaches to the characterisation of material properties. Here the authors demonstrate the retrieval of phase information in far-field intensity profiles by means of an interferometric technique using helical neutron waves.

As part of the modENCODE initiative, which aims to characterize functional DNA elements in D. melanogaster and C. elegans, this study presents a genome-wide chromatin landscape of the fruitfly, based on 18 histone modifications. Nine prevalent chromatin states are described. Integrating these analyses with other data types reveals individual characteristics of different genomic elements. The work provides a resource of unprecedented scale for future experimental investigations.

The study finds coherent spin waves, generated by ultrafast laser pulses, drive antiferromagnetic domain walls (DWs) in Sr₂Cu₃O₄Cl₂ at a record  ~50 km/s. DW propagation direction is controllable via laser helicity and DW winding number, explained by in-plane magnon mode-induced dynamics unique to easy-plane anisotropy magnets.

This study maps chromatin accessibility in neurons and glia in schizophrenia, revealing fetal-like regulatory patterns in adult neurons enriched for genetic risk variants, linking early brain development to schizophrenia pathogenesis

Squeezed light field microscopy (SLIM) combines ideas from tomography and compressed sensing with light field microscopy to enable volumetric imaging at kilohertz rates, as demonstrated in blood flow imaging in zebrafish and voltage imaging in leeches and mice.

By leveraging the power of pretrained DNA foundation models, SegmentNT achieves performant genome annotation through segmenting different genic and regulatory elements.

This study presents an extensive molecular characterization of the reprograming process by analysis of transcriptomic, epigenomic and proteomic data sets describing the routes to pluripotency; it finds distinct routes towards two stable pluripotent states characterized by distinct epigenetic events.

Genetic and physical maps for the 16 chromosomes of Saccharomyces cerevisiae are presented. The genetic map is the result of 40 years of genetic analysis. The physical map was produced from the results of an international systematic sequencing effort. The data for the maps are accessible electronically from the Saccharomyces Genome Database (SGD: http://genome-www.stanford.edu/Saccharomyces/).

In the randomized phase 3 AMPLITUDE trial, patients with HRR-deficient mCSPC experienced longer progression-free survival when they were treated with niraparib and AAP compared to placebo and AAP.

The epigenetic mechanisms underlying phenotypic diversity across different metastatic sites in castration-resistant prostate cancer (CRPC) remain to be characterised. Here, multi-omic profiling across metastatic lesions identifies regulatory networks driving tumour lineage programs and potential therapeutic targets.

Genome-wide analyses in over one million self-reported cases and controls identify genetic variants associated with stuttering and find genetic correlations with autism, depression and impaired musical rhythm, supporting a potential neurological basis for stuttering.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Testicular germ cell tumors are highly heritable, and the authors present the largest genome association study, identifying 22 novel loci, which account for a third of those identified to date. Implicated pathways include male germ cell development and differentiation, and chromosomal segregation.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

How the cardiac myocyte epigenome is rearranged during development, postnatal maturation and disease is not well understood. Here, the authors investigate the human cardiac myocyte epigenome during development and chronic heart failure and identify distinct epigenetic programs regulating these processes.

Elevated expression of long noncoding RNA H19 is seen in clinical samples of neuroendocrine prostate cancer (PCa). Here the authors show H19 promotes plasticity from luminal to neuroendocrine by epigenetic reprogramming.

The genetic architecture underlying Sjögren’s syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.

MLLT3 is identified as a crucial regulator of the self-renewal of human haematopoietic stem cells, and helps to maintain an active chromatin state in haematopoietic stem-cell regulatory genes during culture.

Pilcher et al. present a single-cell transcriptomics-based immune atlas of participants with newly diagnosed multiple myeloma, reporting on the association of cell types, gene expression and intercellular interactions with disease progression phenotypes.