Closing the loops: chromatin loop dynamics after DNA damage DOI Creative Commons
Pierre‐Alexandre Vidi, Jing Liu, Keith Bonin

et al.

Nucleus, Journal Year: 2024, Volume and Issue: 16(1)

Published: Dec. 25, 2024

Chromatin is a dynamic polymer in constant motion. These motions are heterogeneous between cells and within individual cell nuclei profoundly altered response to DNA damage. The shifts chromatin following genomic insults depend on the temporal physical scales considered. They also distinct damaged undamaged regions. In this review, we emphasize role of tethering loop formation dynamics, with view that pulsing loops key contributors motions. tethers likely mediate micron-scale coherence predicted by models measured experimentally, propose remodeling breaks enables uncoupling

Language: Английский

Genome modeling and design across all domains of life with Evo 2 DOI Creative Commons
Garyk Brixi, Matthew G. Durrant, Ja‐Lok Ku

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

Abstract All of life encodes information with DNA. While tools for sequencing, synthesis, and editing genomic code have transformed biological research, intelligently composing new systems would also require a deep understanding the immense complexity encoded by genomes. We introduce Evo 2, foundation model trained on 9.3 trillion DNA base pairs from highly curated atlas spanning all domains life. train 2 7B 40B parameters to an unprecedented 1 million token context window single-nucleotide resolution. learns sequence alone accurately predict functional impacts genetic variation—from noncoding pathogenic mutations clinically significant BRCA1 variants—without task-specific finetuning. Applying mechanistic interpretability analyses, we reveal that autonomously breadth features, including exon–intron boundaries, transcription factor binding sites, protein structural elements, prophage regions. Beyond its predictive capabilities, generates mitochondrial, prokaryotic, eukaryotic sequences at genome scale greater naturalness coherence than previous methods. Guiding via inference-time search enables controllable generation epigenomic structure, which demonstrate first scaling results in biology. make fully open, parameters, training code, inference OpenGenome2 dataset, accelerate exploration design complexity.

Language: Английский

Citations

1
Temporal dynamics of woolly mammoth genome erosion prior to extinction DOI Creative Commons
Marianne Dehasque, Hernán E. Morales, David Díez‐del‐Molino

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(14), P. 3531 - 3540.e13

Published: June 27, 2024

A number of species have recently recovered from near-extinction. Although these avoided the immediate extinction threat, their long-term viability remains precarious due to potential genetic consequences population declines, which are poorly understood on a timescale beyond few generations. Woolly mammoths (Mammuthus primigenius) became isolated Wrangel Island around 10,000 years ago and persisted for over 200 generations before becoming extinct 4,000 ago. To study evolutionary processes leading up mammoths' extinction, we analyzed 21 Siberian woolly mammoth genomes. Our results show that quickly severe bottleneck remained demographically stable during ensuing six millennia. We find mildly deleterious mutations gradually accumulated, whereas highly were purged, suggesting ongoing inbreeding depression lasted hundreds The time-lag between demographic recovery has wide-ranging implications conservation management bottlenecked populations.

Language: Английский

Citations

5
Reframing Formalin: A Molecular Opportunity Enabling Historical Epigenomics and Retrospective Gene Expression Studies DOI Creative Commons
Clare E. Holleley, Erin E. Vaughn

Molecular Ecology Resources, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Formalin preservation of museum specimens has long been considered a barrier to molecular research due extensive crosslinking and chemical modification. However, recent optimisation hot alkaline lysis proteinase K digestion DNA extraction methods have enabled growing number studies overcome these challenges conduct genome-wide re-sequencing targeted locus-specific sequencing. The newest, perhaps most unexpected utility formalin in archival samples is its ability preserve situ DNA-protein interactions at level. Retrieving this signal provides information about the relative compaction or accessibility genome transcriptional machinery required for gene expression. Thus, exposure essentially corresponds taking snapshot organism-wide expression time death. While methylation RNA-Seq analyses dried tissues provided glimpses into historical regulation, techniques were previously limited skeletal desiccated remains, offering only partial insights. By examining fluid-preserved specimens, tools can now be applied broader range tissues, enabling more detailed tissue-specific regulation profiling across vertebrates. In review, we chronicle use formaldehyde collections discuss how chromatin with assays like MNase-seq FAIRE-seq are surmounting fixation unlocking invaluable insights genomes profiles. deeper integration genetics bridges gap between past present vital tool that could help us predict mitigate some impacts future environmental change, novel pathogens, invasive species.

Language: Английский

Citations

0
EXPERIMENTAL SEARCH AN UNDERLYING BASIS OF PRINCIPLES FOR MICROBIOLOGICAL QUANTITATIVE ASSESSMENT OF PRESERVATIVE SOLUTIONS DOI

V.P. Panin,

N.R. Emer

Problems of Biological Medical and Pharmaceutical Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 56 - 60

Published: Jan. 11, 2025

Introduction. Microbiological control of preservative solutions and assessment the state anatomical preparations are topical issues, solution which requires adaptation methods for quantitative determination level microbial contamination to special conditions equilibrium systems containing biological preparations. The aim study is screening, experimental testing microbiological monitoring purity using Melnikov–Razvedenkov as an example. Material methods. object was modified by Scientific Research Center Biomedical Technologies All-Russian Institute Medicinal Aromatic Plants. used on agar nutrient media. Results. As a result comparative analysis contamination, most promising methodological approaches were identified adapted Melnikov-Razvedenkov solution. Conclusions. showed feasibility membrane vacuum filtration method with filters made mixture cellulose acetate nitrate nominal pore diameter 0.45 μm. For sterilization test solution, use through 0.22 μm promising.

Language: Английский

Citations

0
Unveiling Multi‐Scale Architectural Features in Single‐Cell Hi‐C Data Using scCAFE DOI Creative Commons
Fuzhou Wang, Jiecong Lin, Hamid Alinejad‐Rokny

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Abstract Single‐cell Hi‐C (scHi‐C) has provided unprecedented insights into the heterogeneity of 3D genome organization. However, its sparse and noisy nature poses challenges for computational analyses, such as chromatin architectural feature identification. Here, scCAFE is introduced, which a deep learning model multi‐scale detection features at single‐cell level. provides unified framework annotating loops, TAD‐like domains (TLDs), compartments across individual cells. This outperforms previous scHi‐C loop calling methods delivers accurate predictions TLDs that are biologically consistent with studies. The resulting annotations also offer measure to characterize different levels cell types. then leveraged identify series marker anchors, demontrating potential data annotate identities without aid simultaneously sequenced omics data. Overall, not only serves useful tool analyzing genomic architecture, but paves way precise cell‐type solely based on features.

Language: Английский

Citations

0
Neuronal enhancers fine-tune adaptive circuit plasticity DOI
Eric C. Griffith, Anne E. West, Michael E. Greenberg

et al.

Neuron, Journal Year: 2024, Volume and Issue: 112(18), P. 3043 - 3057

Published: Aug. 28, 2024

Language: Английский

Citations

3
Emerging methods and applications in 3D genomics DOI Creative Commons
Simona Pedrotti,

Ilaria Castiglioni,

Cynthia Perez-Estrada

et al.

Current Opinion in Cell Biology, Journal Year: 2024, Volume and Issue: 90, P. 102409 - 102409

Published: Aug. 22, 2024

Since the advent of Hi-C in 2009, a plethora high-throughput sequencing methods have emerged to profile three-dimensional (3D) organization eukaryotic genomes, igniting era 3D genomics. In recent years, genomic resolution achievable by these approaches has dramatically increased and several single-cell versions been developed. Moreover, new repertoire tools not based on proximity ligation digested chromatin emerged, enabling investigation higher-order nucleus. this review, we summarize expanding portfolio technologies, highlighting developments applications from past three years. Lastly, present an outlook where technology-driven field might be headed.

Language: Английский

Citations

1
First fossil chromosomes discovered in freeze-dried mammoth skin DOI
Giorgia Guglielmi

Nature, Journal Year: 2024, Volume and Issue: 631(8022), P. 719 - 720

Published: July 11, 2024

Language: Английский

Citations

0
3D genome organization under extreme metabolic adaptation shows variations in genome compartmentalization and looping DOI Creative Commons
Tathagata Biswas, Hua Li, Nicolas Rohner

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 2, 2024

The cave morphs of Astyanax mexicanus adapt to caves through distinct metabolic and morphological traits. While changed gene expression is a primary driver these adaptations, the underlying role 3D genome organization - key regulator remains unexplored. We analyzed liver architecture in surface identified cave-specific signatures which, when integrated with transcriptomic epigenetic data, associated changes genes metabolism. In this study, comparing within same species, we established foundation for better understanding how may drive phenotypic diversity.

Language: Английский

Citations

0
Viral metagenomics of 100-year-old museum specimens highlights the long-term stability of RNA DOI Creative Commons
Alexandra Keene, Mark D. Stenglein

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 3, 2024

ABSTRACT Recovery of virus sequences from old samples provides an opportunity to study evolution and reconstruct historic virus-host interactions. Studies have mainly relied on DNA or RNA fixed frozen samples. The millions specimens in natural history museums represent a potential treasure trove sequences, but it is not clear how well survives We experimentally assessed the stability insects stored dry at room temperature over 72 weeks. Although molecules grew fragmented, yields remained surprisingly constant. RT-qPCR host showed minimal differences between dried specimens. To assess survival much older we acquired Drosophila North American entomological collections. recovered known novel viruses including several coding complete genomes fly collected 1908. found that virome D. melanogaster has changed little past century. Galbut virus, most prevalent infection contemporary , was also common Finally, investigated genomic physical features surviving RNA. survived chemically damaged, preferentially double stranded contained ribonucleoprotein complexes. This - especially certain types – can survive biological extended periods absence fixation freezing confirms utility provide clearer understanding evolution.

Language: Английский

Citations

0