SEE: A Method for Predicting the Dynamics of Chromatin Conformation Based on Single‐Cell Gene Expression DOI Creative Commons
Minghong Li, Yurong Yang, Rongfeng Wu

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Abstract The dynamics of chromatin conformation involve continuous and reversible changes within the nucleus a cell, which participate in regulating processes such as gene expression, DNA replication, damage repair. Here, SEE is introduced, an artificial intelligence (AI) method that utilizes autoencoder transformer techniques to analyze using single‐cell RNA sequencing data limited number Hi‐C maps. employed investigate across different scales, enabling detection (i) rearrangements topologically associating domains (TADs), (ii) oscillations interactions at loci. Additionally, facilitates interpretation disease‐associated single‐nucleotide polymorphisms (SNPs) by leveraging dynamic features conformation. Overall, offers single‐cell, high‐resolution approach analyzing both developmental disease contexts.

Язык: Английский

Linking genome structures to functions by simultaneous single-cell Hi-C and RNA-seq DOI
Zhiyuan Liu, Yujie Chen, Qimin Xia

и другие.

Science, Год журнала: 2023, Номер 380(6649), С. 1070 - 1076

Опубликована: Июнь 8, 2023

Much progress has been made recently in single-cell chromosome conformation capture technologies. However, a method that allows simultaneous profiling of chromatin architecture and gene expression not reported. Here, we developed an assay named "Hi-C RNA-seq employed simultaneously" (HiRES) performed it on thousands single cells from developing mouse embryos. Single-cell three-dimensional genome structures, despite being heavily determined by the cell cycle developmental stages, gradually diverged type-specific manner as development progressed. By comparing pseudotemporal dynamics interactions with expression, found widespread rewiring occurred before transcription activation. Our results demonstrate establishment specific is tightly related to transcriptional control functions during lineage specification.

Язык: Английский

Процитировано

80
Simultaneous single-cell three-dimensional genome and gene expression profiling uncovers dynamic enhancer connectivity underlying olfactory receptor choice DOI Creative Commons
Honggui Wu, Jiankun Zhang, Fanchong Jian

и другие.

Nature Methods, Год журнала: 2024, Номер 21(6), С. 974 - 982

Опубликована: Апрель 15, 2024

Abstract The simultaneous measurement of three-dimensional (3D) genome structure and gene expression individual cells is critical for understanding a genome’s structure–function relationship, yet this challenging existing methods. Here we present ‘Linking mRNA to Chromatin Architecture (LiMCA)’, which jointly profiles the 3D transcriptome with exceptional sensitivity from low-input materials. Combining LiMCA our high-resolution scATAC-seq assay, METATAC, successfully characterized chromatin accessibility, as well paired structures information, developing olfactory sensory neurons. We expanded repertoire known receptor (OR) enhancers discovered unexpected rules their dynamics: OR genes are most accessible during early differentiation. Furthermore, revealed dynamic spatial relationship between ORs behind stepwise expression. These findings offer valuable insights into how connectivity dynamically orchestrate ‘one neuron–one receptor’ selection process.

Язык: Английский

Процитировано

35
Advances in single-cell omics and multiomics for high-resolution molecular profiling DOI Creative Commons

Jongsu Lim,

Chanho Park, Minjae Kim

и другие.

Experimental & Molecular Medicine, Год журнала: 2024, Номер 56(3), С. 515 - 526

Опубликована: Март 5, 2024

Abstract Single-cell omics technologies have revolutionized molecular profiling by providing high-resolution insights into cellular heterogeneity and complexity. Traditional bulk approaches average signals from heterogeneous cell populations, thereby obscuring important nuances. studies enable the analysis of individual cells reveal diverse types, dynamic states, rare populations. These techniques offer unprecedented resolution sensitivity, enabling researchers to unravel landscape cells. Furthermore, integration multimodal data within a single provides comprehensive holistic view processes. By combining multiple dimensions, can facilitate elucidation complex interactions, regulatory networks, mechanisms. This integrative approach enhances our understanding systems, development disease. review an overview recent advances in single-cell for profiling. We discuss principles methodologies representatives each method, highlighting strengths limitations different techniques. In addition, we present case demonstrating applications various fields, including developmental biology, neurobiology, cancer research, immunology, precision medicine.

Язык: Английский

Процитировано

34
Single-cell multiplex chromatin and RNA interactions in ageing human brain DOI Creative Commons
Xingzhao Wen, Zhifei Luo,

Wenxin Zhao

и другие.

Nature, Год журнала: 2024, Номер 628(8008), С. 648 - 656

Опубликована: Март 27, 2024

Abstract Dynamically organized chromatin complexes often involve multiplex interactions and sometimes chromatin-associated RNA 1–3 . Chromatin complex compositions change during cellular differentiation ageing, are expected to be highly heterogeneous among terminally differentiated single cells 4–7 Here we introduce the multinucleic acid interaction mapping in (MUSIC) technique for concurrent profiling of interactions, gene expression RNA–chromatin associations within individual nuclei. When applied 14 human frontal cortex samples from older donors, MUSIC delineated diverse cortical cell types states. We observed that nuclei exhibiting fewer short-range were correlated with both an ‘older’ transcriptomic signature Alzheimer’s disease pathology. Furthermore, type contacts between cis quantitative trait loci a promoter tends which these specifically affect their target gene. In addition, female exhibit XIST non-coding chromosome X, along spatial organizations X chromosomes. presents potent tool exploration architecture transcription at resolution tissues.

Язык: Английский

Процитировано

24
GAGE-seq concurrently profiles multiscale 3D genome organization and gene expression in single cells DOI
Tianming Zhou, Ruochi Zhang, Deyong Jia

и другие.

Nature Genetics, Год журнала: 2024, Номер 56(8), С. 1701 - 1711

Опубликована: Май 14, 2024

Язык: Английский

Процитировано

23
Epigenetic regulatory layers in the 3D nucleus DOI Creative Commons
Andréa Willemin, Dominik Szabó, Ana Pombo

и другие.

Molecular Cell, Год журнала: 2024, Номер 84(3), С. 415 - 428

Опубликована: Янв. 18, 2024

Nearly 7 decades have elapsed since Francis Crick introduced the central dogma of molecular biology, as part his ideas on protein synthesis, setting fundamental rules sequence information transfer from DNA to RNAs and proteins. We learned that gene expression is finely tuned in time space, due activities proteins regulatory elements, through cell-type-specific three-dimensional conformations genome. Here, we review major advances genome biology discuss a set regulation highlight how various biomolecular assemblies lead formation structural features within nucleus, with roles transcriptional control. conclude by suggesting further developments will help capture complex, dynamic, often spatially restricted events govern mammalian cells.

Язык: Английский

Процитировано

19
Droplet Hi-C enables scalable, single-cell profiling of chromatin architecture in heterogeneous tissues DOI Creative Commons
Lei Chang, Yang Xie, Brett M. Taylor

и другие.

Nature Biotechnology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 18, 2024

Abstract Current methods for analyzing chromatin architecture are not readily scalable to heterogeneous tissues. Here we introduce Droplet Hi-C, which uses a commercial microfluidic device high-throughput, single-cell conformation profiling in droplets. Using mapped the of mouse cortex and analyzed gene regulatory programs major cortical cell types. In addition, used this technique detect copy number variations, structural variations extrachromosomal DNA human glioblastoma, colorectal blood cancer cells, revealing clonal dynamics other oncogenic events during treatment. We refined allow joint transcriptome single facilitating exploration links between expression both normal tissues tumors. Thus, Hi-C addresses critical gaps analysis enhances understanding regulation.

Язык: Английский

Процитировано

12
scmFormer Integrates Large‐Scale Single‐Cell Proteomics and Transcriptomics Data by Multi‐Task Transformer DOI Creative Commons
Jing Xu,

De‐Shuang Huang,

Xiujun Zhang

и другие.

Advanced Science, Год журнала: 2024, Номер 11(19)

Опубликована: Март 14, 2024

Abstract Transformer‐based models have revolutionized single cell RNA‐seq (scRNA‐seq) data analysis. However, their applicability is challenged by the complexity and scale of single‐cell multi‐omics data. Here a novel multi‐modal/multi‐task transformer (scmFormer) proposed to fill up existing blank integrating proteomics with other omics Through systematic benchmarking, it demonstrated that scmFormer excels in large‐scale multimodal heterogeneous multi‐batch paired data, while preserving shared information across batchs distinct biological information. achieves 54.5% higher average F1 score compared second method transferring cell‐type labels from transcriptomics Using COVID‐19 datasets, presented successfully integrates over 1.48 million cells on personal computer. Moreover, also proved performs better than methods generating unmeasured modality well‐suited for spatial multi‐omic Thus, powerful comprehensive tool analyzing

Язык: Английский

Процитировано

10
An extrinsic motor directs chromatin loop formation by cohesin DOI Creative Commons
Thomas M Guérin, Christopher Barrington, Georgii Pobegalov

и другие.

The EMBO Journal, Год журнала: 2024, Номер 43(19), С. 4173 - 4196

Опубликована: Авг. 19, 2024

Язык: Английский

Процитировано

10
Single‐Cell Hi‐C Technologies and Computational Data Analysis DOI Creative Commons
Madison Dautle, Yong Chen

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Abstract Single‐cell chromatin conformation capture (scHi‐C) techniques have evolved to provide significant insights into the structural organization and regulatory mechanisms in individual cells. Although many scHi‐C protocols been developed, they often involve intricate procedures resulting data are sparse, leading computational challenges for systematic analysis limited applicability. This review provides a comprehensive overview, quantitative evaluation of thirteen practical guidance on topics. It is first assessed efficiency these based total number contacts recovered per cell cis/trans ratio. then provided considerations quality control imputation. Additionally, capabilities implementations various methods, covering clustering, A/B compartment calling, topologically associating domain (TAD) loop 3D reconstruction, simulation differential interaction summarized. further highlighted key associated with specific complexities propose potential solutions.

Язык: Английский

Процитировано

1