scholarly journals GEM: A manifold learning based framework for reconstructing spatial organizations of chromosomes

2017 ◽  
Author(s):  
Guangxiang Zhu ◽  
Wenxuan Deng ◽  
Hailin Hu ◽  
Rui Ma ◽  
Sai Zhang ◽  
...  
Keyword(s):  
Manifold Learning ◽  
Learning Strategy ◽  
Genome Structure ◽  
Three Dimensional ◽  
Conformational Energy ◽  
3D Genome ◽  
Learning Framework ◽  
Reconstruction Methods ◽  
Eukaryotic Gene ◽  
Validation Tests

AbstractDecoding the spatial organizations of chromosomes has crucial implications for studying eukaryotic gene regulation. Recently, Chromosomal conformation capture based technologies, such as Hi-C, have been widely used to uncover the interaction frequencies of genomic loci in high-throughput and genome-wide manner and provide new insights into the folding of three-dimensional (3D) genome structure. In this paper, we develop a novel manifold learning framework, called GEM (Genomic organization reconstructor based on conformational Energy and Manifold learning), to elucidate the underlying 3D spatial organizations of chromosomes from Hi-C data. Unlike previous chromatin structure reconstruction methods, which explicitly assume specific relationships between Hi-C interaction frequencies and spatial distances between distal genomic loci, GEM is able to reconstruct an ensemble of chromatin conformations by directly embedding the neigh-boring affinities from Hi-C space into 3D Euclidean space based on a manifold learning strategy that considers both the fitness of Hi-C data and the biophysical feasibility of the modeled structures, which are measured by the conformational energy derived from our current biophysical knowledge about the 3D polymer model. Extensive validation tests on both simulated interaction frequency data and experimental Hi-C data of yeast and human demonstrated that GEM not only greatly outperformed other state-of-art modeling methods but also reconstructed accurate chromatin structures that agreed well with the hold-out or independent Hi-C data and sparse geometric restraints derived from the previous fluorescence in situ hybridization (FISH) studies. In addition, as GEM can generate accurate spatial organizations of chromosomes by integrating both experimentally-derived spatial contacts and conformational energy, we for the first time extended our modeling method to recover long-range genomic interactions that are missing from the original Hi-C data. All these results indicated that GEM can provide a physically and physiologically valid 3D representations of the organizations of chromosomes and thus serve as an effective and useful genome structure reconstructor.

scholarly journals GSDB: a database of 3D chromosome and genome structures reconstructed from Hi-C data

2019 ◽  
Author(s):  
Oluwatosin Oluwadare ◽  
Max Highsmith ◽  
Jianlin Cheng
Keyword(s):  
Structure Prediction ◽  
Biological Activities ◽  
Genome Structure ◽  
3D Structure ◽  
Three Dimensional ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Reconstruction Methods ◽  
A Genome ◽  
Structure Reconstruction

ABSTRACTAdvances in the study of chromosome conformation capture (3C) technologies, such as Hi-C technique - capable of capturing chromosomal interactions in a genome-wide scale - have led to the development of three-dimensional (3D) chromosome and genome structure reconstruction methods from Hi-C data. The 3D genome structure is important because it plays a role in a variety of important biological activities such as DNA replication, gene regulation, genome interaction, and gene expression. In recent years, numerous Hi-C datasets have been generated, and likewise, a number of genome structure construction algorithms have been developed. However, until now, there has been no freely available repository for 3D chromosome structures. In this work, we outline the construction of a novel Genome Structure Database (GSDB) to create a comprehensive repository that contains 3D structures for Hi-C datasets constructed by a variety of 3D structure reconstruction tools. GSDB contains over 50,000 structures constructed by 12 state-of-the-art chromosome and genome structure prediction methods for publicly used Hi-C datasets with varying resolution. The database is useful for the community to study the function of genome from a 3D perspective. GSDB is accessible at http://sysbio.rnet.missouri.edu/3dgenome/GSDB

scholarly journals Repeat elements organize 3D genome structure and mediate transcription in the filamentous fungusEpichloë festucae

2018 ◽  
Author(s):  
David J Winter ◽  
Austen RD Ganley ◽  
Carolyn A Young ◽  
Ivan Liachko ◽  
Christopher L Schardl ◽  
...  
Keyword(s):  
Genome Structure ◽  
Regulation Of Gene Expression ◽  
Three Dimensional ◽  
Structural Features ◽  
Dimensional Structure ◽  
In Planta ◽  
Repeat Elements ◽  
Symbiotic Relationships ◽  
3D Genome ◽  
Transcriptional Changes

AbstractStructural features of genomes, including the three-dimensional arrangement of DNA in the nucleus, are increasingly seen as key contributors to the regulation of gene expression. However, studies on how genome structure and nuclear organization influence transcription have so far been limited to a handful of model species. This narrow focus limits our ability to draw general conclusions about the ways in which three-dimensional structures are encoded, and to integrate information from three-dimensional data to address a broader gamut of biological questions. Here, we generate a complete and gapless genome sequence for the filamentous fungus,Epichloë festucae. Coupling it with RNAseq and HiC data, we investigate how the structure of the genome contributes to the suite of transcriptional changes that anEpichloëspecies needs to maintain symbiotic relationships with its grass host. Our results reveal a unique “patchwork” genome, in which repeat-rich blocks of DNA with discrete boundaries are interspersed by gene-rich sequences. In contrast to other species, the three-dimensional structure of the genome is anchored by these repeat blocks, which act to isolate transcription in neighbouring gene-rich regions. Genes that are differentially expressed in planta are enriched near the boundaries of these repeat-rich blocks, suggesting that their three-dimensional orientation partly encodes and regulates the symbiotic relationship formed by this organism.

scholarly journals Mining 3D genome structure populations identifies major factors governing the stability of regulatory communities

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Chao Dai ◽  
Wenyuan Li ◽  
Harianto Tjong ◽  
Shengli Hao ◽  
Yonggang Zhou ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Genome Structure ◽  
Protein Structures ◽  
Three Dimensional ◽  
Expression Variability ◽  
3D Genome ◽  
Significant Challenge ◽  
The Stability ◽  
Major Factors ◽  
3D Genome Structure

Abstract Three-dimensional (3D) genome structures vary from cell to cell even in an isogenic sample. Unlike protein structures, genome structures are highly plastic, posing a significant challenge for structure-function mapping. Here we report an approach to comprehensively identify 3D chromatin clusters that each occurs frequently across a population of genome structures, either deconvoluted from ensemble-averaged Hi-C data or from a collection of single-cell Hi-C data. Applying our method to a population of genome structures (at the macrodomain resolution) of lymphoblastoid cells, we identify an atlas of stable inter-chromosomal chromatin clusters. A large number of these clusters are enriched in binding of specific regulatory factors and are therefore defined as ‘Regulatory Communities.’ We reveal two major factors, centromere clustering and transcription factor binding, which significantly stabilize such communities. Finally, we show that the regulatory communities differ substantially from cell to cell, indicating that expression variability could be impacted by genome structures.

scholarly journals Rice 3D chromatin structure correlates with sequence variation and meiotic recombination rate

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Agnieszka A. Golicz ◽  
Prem L. Bhalla ◽  
David Edwards ◽  
Mohan B. Singh
Keyword(s):  
Meiotic Recombination ◽  
Recombination Rate ◽  
Sequence Variation ◽  
Genome Structure ◽  
Rice Genome ◽  
Three Dimensional ◽  
3D Genome ◽  
Cellular Processes ◽  
Eukaryotic Species ◽  
Topologically Associated Domains

AbstractGenomes of many eukaryotic species have a defined three-dimensional architecture critical for cellular processes. They are partitioned into topologically associated domains (TADs), defined as regions of high chromatin inter-connectivity. While TADs are not a prominent feature of A. thaliana genome organization, they have been reported for other plants including rice, maize, tomato and cotton and for which TAD formation appears to be linked to transcription and chromatin epigenetic status. Here we show that in the rice genome, sequence variation and meiotic recombination rate correlate with the 3D genome structure. TADs display increased SNP and SV density and higher recombination rate compared to inter-TAD regions. We associate the observed differences with the TAD epigenetic landscape, TE composition and an increased incidence of meiotic crossovers.

scholarly journals ChromeBat: A Bio-Inspired Approach to 3D Genome Reconstruction

2021 ◽  
Author(s):  
Brandon Collins ◽  
Philip N. Brown ◽  
Oluwatosin Oluwadare
Keyword(s):  
Genome Structure ◽  
Three Dimensional ◽  
Genomic Analysis ◽  
Bat Algorithm ◽  
Empirical Measure ◽  
Reconstruction Problem ◽  
Genome Reconstruction ◽  
3D Genome ◽  
A Genome ◽  
Contact Data

Background: With the advent of Next Generation Sequencing and the Hi-C experiment, high quality genome-wide contact data is becoming increasingly available. This data represents an empirical measure of how a genome interacts inside the nucleus. Genome conformation is of particular interest as it has been experimentally shown to be a driving force for many genomic functions from regulation to transcription. Thus, the Three-Dimensional Genome Reconstruction Problem seeks to take Hi-C data and produce the complete physical genome structure as it appears in the nucleus for genomic analysis. Results: We propose and develop a novel method to solve the Chromosome and Genome Reconstruction problem based on the Bat Algorithm which we called ChromeBat.We demonstrate on real Hi-C data that ChromeBat is capable of state of the art performance. Additionally, the domain of Genome Reconstruction has been criticized for lacking algorithmic diversity, and the bio-inspired nature of ChromeBat contributes algorithmic diversity to the problem domain. Conclusions: ChromeBat is an effective approach at solving the Genome Reconstruction Problem. The source code and usage guide can be found here: https://github.com/OluwadareLab/ChromeBat.

scholarly journals L1 and B1 repeats blueprint the spatial organization of chromatin

2019 ◽  
Author(s):  
J. Yuyang Lu ◽  
Lei Chang ◽  
Tong Li ◽  
Ting Wang ◽  
Yafei Yin ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Mammalian Cells ◽  
Spatial Organization ◽  
Genome Structure ◽  
Three Dimensional ◽  
Order Structure ◽  
Basic Principles ◽  
Heterochromatin Protein ◽  
3D Genome ◽  
Genomic Repeats

SUMMARYDespite extensive mapping of three-dimensional (3D) chromatin structures, the basic principles underlying genome folding remain unknown. Here, we report a fundamental role for L1 and B1 retrotransposons in shaping the macroscopic 3D genome structure. Homotypic clustering of B1 and L1 repeats in the nuclear interior or at the nuclear and nucleolar peripheries, respectively, segregates the genome into mutually exclusive nuclear compartments. This spatial segregation of L1 and B1 is conserved in mouse and human cells, and occurs dynamically during establishment of the 3D chromatin structure in early embryogenesis and the cell cycle. Depletion of L1 transcripts drastically disrupts the spatial distributions of L1- and B1-rich compartments. L1 transcripts are strongly associated with L1 DNA sequences and induce phase separation of the heterochromatin protein HP1α. Our results suggest that genomic repeats act as the blueprint of chromatin macrostructure, thus explaining the conserved higher-order structure of chromatin across mammalian cells.

scholarly journals MyoD is a 3D genome structure organizer for muscle cell identity

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Ruiting Wang ◽  
Fengling Chen ◽  
Qian Chen ◽  
Xin Wan ◽  
Minglei Shi ◽  
...  
Keyword(s):  
Muscle Cell ◽  
Genome Organization ◽  
Genome Structure ◽  
Three Dimensional ◽  
Cell Lineage ◽  
Muscle Cells ◽  
Cell Type ◽  
Cell Identity ◽  
3D Genome ◽  
A Genome

AbstractThe genome exists as an organized, three-dimensional (3D) dynamic architecture, and each cell type has a unique 3D genome organization that determines its cell identity. An unresolved question is how cell type-specific 3D genome structures are established during development. Here, we analyzed 3D genome structures in muscle cells from mice lacking the muscle lineage transcription factor (TF), MyoD, versus wild-type mice. We show that MyoD functions as a “genome organizer” that specifies 3D genome architecture unique to muscle cell development, and that H3K27ac is insufficient for the establishment of MyoD-induced chromatin loops in muscle cells. Moreover, we present evidence that other cell lineage-specific TFs might also exert functional roles in orchestrating lineage-specific 3D genome organization during development.

scholarly journals 3D-GNOME 2.0: a three-dimensional genome modeling engine for predicting structural variation-driven alterations of chromatin spatial structure in the human genome

2020 ◽  
Vol 48 (W1) ◽  
pp. W170-W176
Author(s):  
Michal Wlasnowolski ◽  
Michal Sadowski ◽  
Tymon Czarnota ◽  
Karolina Jodkowska ◽  
Przemyslaw Szalaj ◽  
...  
Keyword(s):  
Human Genome ◽  
Conformational Changes ◽  
Genomic Sequence ◽  
Genome Structure ◽  
3D Structure ◽  
Three Dimensional ◽  
Structural Data ◽  
3D Models ◽  
3D Genome ◽  
The One

Abstract Structural variants (SVs) that alter DNA sequence emerge as a driving force involved in the reorganisation of DNA spatial folding, thus affecting gene transcription. In this work, we describe an improved version of our integrated web service for structural modeling of three-dimensional genome (3D-GNOME), which now incorporates all types of SVs to model changes to the reference 3D conformation of chromatin. In 3D-GNOME 2.0, the default reference 3D genome structure is generated using ChIA-PET data from the GM12878 cell line and SVs data are sourced from the population-scale catalogue of SVs identified by the 1000 Genomes Consortium. However, users may also submit their own structural data to set a customized reference genome structure, and/or a custom input list of SVs. 3D-GNOME 2.0 provides novel tools to inspect, visualize and compare 3D models for regions that differ in terms of their linear genomic sequence. Contact diagrams are displayed to compare the reference 3D structure with the one altered by SVs. In our opinion, 3D-GNOME 2.0 is a unique online tool for modeling and analyzing conformational changes to the human genome induced by SVs across populations. It can be freely accessed at https://3dgnome.cent.uw.edu.pl/.

scholarly journals ChromeBat: A Bio-Inspired Approach to 3D Genome Reconstruction

Genes ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1757
Author(s):  
Brandon Collins ◽  
Oluwatosin Oluwadare ◽  
Philip Brown
Keyword(s):  
Genome Structure ◽  
Three Dimensional ◽  
Genomic Analysis ◽  
Bat Algorithm ◽  
Empirical Measure ◽  
Reconstruction Problem ◽  
Genome Reconstruction ◽  
3D Genome ◽  
A Genome ◽  
Contact Data

With the advent of Next Generation Sequencing and the Hi-C experiment, high quality genome-wide contact data are becoming increasingly available. These data represents an empirical measure of how a genome interacts inside the nucleus. Genome conformation is of particular interest as it has been experimentally shown to be a driving force for many genomic functions from regulation to transcription. Thus, the Three Dimensional-Genome Reconstruction Problem (3D-GRP) seeks to take Hi-C data and produces a complete physical genome structure as it appears in the nucleus for genomic analysis. We propose and develop a novel method to solve the Chromosome and Genome Reconstruction problem based on the Bat Algorithm (BA) which we called ChromeBat. We demonstrate on real Hi-C data that ChromeBat is capable of state-of-the-art performance. Additionally, the domain of Genome Reconstruction has been criticized for lacking algorithmic diversity, and the bio-inspired nature of ChromeBat contributes algorithmic diversity to the problem domain. ChromeBat is an effective approach for solving the Genome Reconstruction Problem.

Dysregulation of HOX as a Potential Therapeutic Target in Breast Cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Ji-Yeon Lee ◽  
Myoung Hee Kim
Keyword(s):  
Breast Cancer ◽  
Hox Genes ◽  
Therapeutic Potential ◽  
Expression Patterns ◽  
Genome Structure ◽  
Control Cell ◽  
Three Dimensional ◽  
Cellular Processes ◽  
Hox Protein

: HOX genes belong to the highly conserved homeobox superfamily, responsible for the regulation of various cellular processes that control cell homeostasis, from embryogenesis to carcinogenesis. The abnormal expression of HOX genes is observed in various cancers, including breast cancer; they act as oncogenes or as suppressors of cancer, according to context. In this review, we analyze HOX gene expression patterns in breast cancer and examine their relationship, based on the three-dimensional genome structure of the HOX locus. The presence of non-coding RNAs, embedded within the HOX cluster, and the role of these molecules in breast cancer have been reviewed. We further evaluate the characteristic activity of HOX protein in breast cancer and its therapeutic potential.

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