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Extrachromosomal circular DNAs (ecDNAs) are prevalent in human cancers and are thought to drive tumor evolution and drug resistance by amplifying oncogenes. Here, authors develop ec3D to reconstruct three-dimensional ecDNA structures, revealing how their spatial organization rewires regulatory circuits.

Human genetic loci that associate with composition of the oral microbiome are identified using saliva-derived DNA, where the same host genetics also shapes oral health and genetic variation in oral bacteria.

In the nematode C. elegans, cohesin creates specifically at active enhancers chromatin 3D structures named fountains. Cohesin artificial cleavage disrupts fountains and changes neuronal gene expression, function and animal behavior.

A technique called condense-seq has been developed to measure nucleosome condensability and used to show that mononucleosomes contain sufficient information to condense into large-scale compartments without requiring any external factors.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

A single-cell epigenomic atlas of human immune cells highlights cell-type-specific features associated with genetic or environmental exposures.

Soil microbial populations bloom and then die-off in ecosystems with seasonal snowpack. This study showed that distinct taxa utilize different N sources for growth or energy during the microbial bloom and alter the fate of N after snowmelt.

Fragmentation patterns of cell-free DNA are a promising biomarker source, however, correlations with different cancer types are heterogenous. Here, the authors develop LIONHEART to enable detection of 14+ cancer types from whole genome sequenced cell-free DNA.

CLASSIC is a high-throughput genetic profiling platform that combines long- and short-read next-generation-sequencing modalities to quantitatively assess pools of constructs of arbitrary length containing diverse genetic part compositions.

Calcium imaging of mouse hippocampal neurons while mice learn a reward-based task over several weeks provides insight into the evolution of the hippocampal reward representation during extended periods of experience.

This study investigates a calcium-permeable AMPAR–gated microcircuit in the nucleus accumbens during social bonding in prairie voles. By showing that disrupting calcium-permeable AMPAR signaling impairs ensemble-level encoding despite increasing single-neuron selectivity, the work reveals how coordinated ensemble dynamics transform social interaction into enduring attachment.

Here, the authors analyze the microbiome composition and resistome pre-, during- and post-antibiotic exposure in Malawian adults, and find that commonly used antibiotics, such as ceftriaxone, exert strong off-target effects, both increasing abundance of opportunistic pathogens and the prevalence of a wide number of antibiotic resistance genes.

Schooley et al. find that mitotically bookmarked loci drive a transient chromosome folding state during G1 entry that is subsequently modulated by factors inherited through the cytoplasm.

Karagyozova at al. reveal that the histone H3.3 chaperone HIRA impacts higher-order spatial arrangement of chromatin, independently from its role in regulating early replication, providing a model to disentangle long-standing correlations between early replication, accessibility, typical histone marks and A compartment.

Cultivation of tropical soil microorganisms combined with physiological experiments and bioinformatics analyses identify a family of clade III lactonase-type nitrous oxide reductases with low sequence identity but high 3D structural similarity to known nitrous oxide reductases.

LSFM imaging revealed 3D islet maps: GADA+ cases mirrored controls, while short-duration T1D showed loss of small INS + GCG– islets but preserved larger mixed INS + GCG+ ones, highlighting islet size- and composition-dependent vulnerability

Neural population activity in the medial entorhinal cortex of mice can be organized into ultraslow oscillatory sequences, with periods extending up to the minute range.

An approach combining BONCAT, stable isotope probing and metaproteomics showcases the hidden metabolic interconnectivity of microorganisms within an anaerobic digestion community.

CRISPR activators are powerful tools for controlling gene expression, but they suffer from inconsistent efficacy and high toxicity. Here, authors develop a high-throughput method to test thousands of CRISPR activators, revealing distinct principles of activator biology and delivering improved tools.

The authors develop a supervised and unsupervised learning algorithm Signature. Machine learning and network model analysis of Hi-C datasets across 62 2n genomes suggest that inter-chromosomal contacts demarcate genome topology along a spatial gradient of genome activity.

Here, the authors present SemiBin, a siamese deep neural network framework that incorporates information from reference genomes, able to extract better metagenome-assembled genomes (MAGs) in several host-associated and environmental habitats.

HiScanner, a tool for identification of copy number alterations from single cell whole-genome sequencing data, uncovers cell-type-specific somatic mosaicism in human brain and offers a way to track clonal evolution at the single cell resolution.

Here, Johansen et al. develop an approach, Phages from Metagenomics Binning (PHAMB), that allows the binning of thousands of viral genomes directly from bulk metagenomics data, while simultaneously enabling clustering of viral genomes into accurate taxonomic viral populations, unveiling viral-microbial host interactions in the gut.

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.

DREDge is a software tool for motion correction of high-density electrophysiology recordings. It can handle action potential or local field potential data and is demonstrated on a variety of acute or chronic recordings from humans, nonhuman primates and mice.

Single-cell Proliferation Rate Inference in Non-homogeneous Tumors through Evolutionary Routes (SPRINTER) allows users to infer proliferation rates of individual clones within a tumor from single-cell DNA sequencing data. Applying SPRINTER to human tumor datasets highlighted a link between proliferation and metastatic potential.

In this work the authors present an approach called ProFlex which compresses flexibility information from protein structures via normal mode analysis, enabling scalable insights into protein dynamics and function through a novel structural alphabet.

A high-resolution transcriptomic and epigenomic cell-type atlas of the developing mouse visual cortex from embryonic to postnatal development is presented, providing a real-time dynamic molecular map associated with individual cell types and specific developmental events.

Using two-photon microscopy with a panoramic virtual reality setup, how head direction cells in larval zebrafish integrate visual landmarks and optic flow to track orientation is revealed.

The authors show that H3K36 methylation preserves enhancer activity and chromatin structure. Its loss redistributes repressive marks, disrupts 3D genome organization, and destabilizes the epigenome.

Ginhoux and colleagues perform multi-omic characterization of hepatocellular carcinoma and identify an onco-fetal niche that includes fibroblasts, macrophages and endothelial cells and influences immunotherapy response and relapse.

Here, the authors describe scDEEP-mC, an improved single-cell whole-genome bisulfite sequencing method for complex libraries and deep genomic coverage, and show advanced analyses of allele-specific methylation, replication dynamics, and X-inactivation.

Dinosaurs became extinct 65 million years ago due to volcanism and a bolide impact, but whether their numbers were already declining is still not clear. This study calculates the morphological disparity of seven dinosaur subgroups, showing that at least some groups were in a long-term decline before the extinction.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

Examination of the neural activity in the basolateral amygdala and ventral CA1 of mice during tasks or rest following exposure to social stress reveals signatures of resilience and susceptibility to stress.

Building on a nucleosome-depletion strategy, DEFND-seq utilizes a droplet microfluidic platform to enable high-throughput co-profiling of DNA and RNA in single cells.

Single-molecule chromatin fiber sequencing exposes single-cell-level heterogeneity in the chromatin architecture of individual regulatory elements.

Drakopoulos et al. present a model that captures the transformation from sound waves to neural activity patterns underlying early auditory processing. The model reproduces neural responses to a range of complex sounds and key neurophysiological phenomena.

Here the authors present a tool that enables a flexible set of existing binning algorithms to be combined, resulting in improved binning accuracy and the recovery of more near-complete genomes from metagenomes compared to standalone methods.

Here the authors functionally test and resolve the spatial genome organization of cis-regulatory elements and genetic variants in atrial, ventricular, and failing human cardiomyocytes and linked them to heart disease traits, including QT syndrome.

This work presents a global wind power simulation tool that uses high-resolution data and extensive validation to improve accuracy. It corrects wind speed biases and validates against real-world data, enhancing reliability for wind energy assessments across various scales and regions.

Kim, Wang, Clow and colleagues show that long-range chromatin loops bringing distal enhancers or super-enhancers together with promoters are cohesin dependent and cell type specific, whereas most short-range and promoter-centric transcriptional loops are cohesin independent and constitutive.

By mapping oxidatively damaged bases and abasic sites at single-nucleotide resolution in human cells, Takhaveev et al. observed transcription-related strand biases, patterns mirroring cancer mutational signatures, and captured the action of the anticancer drug irofulven.

Carty et al. identify the H3K9 methyltransferases that restrict the size and position of the centromere protein A chromatin domain, maintaining functional centromeres.

Understanding the cellular origins of cancers is crucial for improving diagnosis and treatment. Here, the authors utilize single cell chromatin accessibility data, patient whole-genome sequencing mutational profiles, and machine learning to predict the cell of origin for 37 cancer types, providing insights into cancer development and therapeutic strategies.

JWST data show that the exoplanet WASP-18b has thermally distinct regions of its dayside. The authors mapped the sizes of these regions, measured their temperatures and potentially identify water destruction in the hottest region.

Mammalian oocytes and embryos undergo major epigenetic changes. Here, genome-wide mapping of the histone variant H2A.Z across mouse oogenesis and early embryogenesis reveals distinct maternal, embryonic and persistent enrichment patterns, linking histone variant dynamics to epigenetic inheritance, repeats and developmental reprogramming.

DNA replication in the human genome occurs preferentially at initiation zones (IZs). Here, the authors identify TRESLIN-MTBP as a limiting factor for replication initiation whose loading onto DNA-bound MCM defines IZs. This process establishes IZs and replication timing in human cells.