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https://www.readbyqxmd.com/read/29149264/sim3c-simulation-of-hi-c-and-meta3c-proximity-ligation-sequencing-technologies
#1
Matthew Z DeMaere, Aaron E Darling
Background: Chromosome conformation capture (3C) and Hi-C DNA sequencing methods have rapidly advanced our understanding of the spatial organization of genomes and metagenomes. Many variants of these protocols have been developed, each with their own strengths. Currently there is no systematic means for simulating sequence data from this family of sequencing protocols, potentially hindering the advancement of algorithms to exploit this new datatype. Findings: We describe a computational simulator that, given simple parameters and reference genome sequences, will simulate Hi-C sequencing on those sequences...
November 15, 2017: GigaScience
https://www.readbyqxmd.com/read/29148971/convergence-of-topological-domain-boundaries-insulators-and-polytene-interbands-revealed-by-high-resolution-mapping-of-chromatin-contacts-in-the-early-drosophila-melanogaster-embryo
#2
Michael R Stadler, Jenna E Haines, Michael Eisen
High-throughput assays of three-dimensional interactions of chromosomes have shed considerable light on the structure of animal chromatin. Despite this progress, the precise physical nature of observed structures and the forces that govern their establishment remain poorly understood. Here we present high resolution Hi-C data from early Drosophila embryos. We demonstrate that boundaries between topological domains of various sizes map to DNA elements that resemble classical insulator elements: short genomic regions sensitive to DNase digestion that are strongly bound by known insulator proteins and are frequently located between divergent promoters...
November 17, 2017: ELife
https://www.readbyqxmd.com/read/29141034/structure-of-the-human-chromosome-interaction-network
#3
Sergio Sarnataro, Andrea M Chiariello, Andrea Esposito, Antonella Prisco, Mario Nicodemi
New Hi-C technologies have revealed that chromosomes have a complex network of spatial contacts in the cell nucleus of higher organisms, whose organisation is only partially understood. Here, we investigate the structure of such a network in human GM12878 cells, to derive a large scale picture of nuclear architecture. We find that the intensity of intra-chromosomal interactions is power-law distributed. Inter-chromosomal interactions are two orders of magnitude weaker and exponentially distributed, yet they are not randomly arranged along the genomic sequence...
2017: PloS One
https://www.readbyqxmd.com/read/29137603/clustertad-an-unsupervised-machine-learning-approach-to-detecting-topologically-associated-domains-of-chromosomes-from-hi-c-data
#4
Oluwatosin Oluwadare, Jianlin Cheng
BACKGROUND: With the development of chromosomal conformation capturing techniques, particularly, the Hi-C technique, the study of the spatial conformation of a genome is becoming an important topic in bioinformatics and computational biology. The Hi-C technique can generate genome-wide chromosomal interaction (contact) data, which can be used to investigate the higher-level organization of chromosomes, such as Topologically Associated Domains (TAD), i.e., locally packed chromosome regions bounded together by intra chromosomal contacts...
November 14, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/29117547/a-prostate-cancer-risk-element-functions-as-a-repressive-loop-that-regulates-hoxa13
#5
Zhifei Luo, Suhn Kyong Rhie, Fides D Lay, Peggy J Farnham
Prostate cancer (PCa) is the leading cancer among men in the United States, with genetic factors contributing to ∼42% of the susceptibility to PCa. We analyzed a PCa risk region located at 7p15.2 to gain insight into the mechanisms by which this noncoding region may affect gene regulation and contribute to PCa risk. We performed Hi-C analysis and demonstrated that this region has long-range interactions with the HOXA locus, located ∼873 kb away. Using the CRISPR/Cas9 system, we deleted a 4-kb region encompassing several PCa risk-associated SNPs and performed RNA-seq to investigate transcriptomic changes in prostate cells lacking the regulatory element...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29113562/utilizing-networks-for-differential-analysis-of-chromatin-interactions
#6
Lu Liu, Jianhua Ruan
Chromatin conformation capture with high-throughput sequencing (Hi-C) is a powerful technique to detect genome-wide chromatin interactions. In this paper, we introduce two novel approaches to detect differentially interacting genomic regions between two Hi-C experiments using a network model. To make input data from multiple experiments comparable, we propose a normalization strategy guided by network topological properties. We then devise two measurements, using local and global connectivity information from the chromatin interaction networks, respectively, to assess the interaction differences between two experiments...
October 19, 2017: Journal of Bioinformatics and Computational Biology
https://www.readbyqxmd.com/read/29106613/3div-a-3d-genome-interaction-viewer-and-database
#7
Dongchan Yang, Insu Jang, Jinhyuk Choi, Min-Seo Kim, Andrew J Lee, Hyunwoong Kim, Junghyun Eom, Dongsup Kim, Inkyung Jung, Byungwook Lee
Three-dimensional (3D) chromatin structure is an emerging paradigm for understanding gene regulation mechanisms. Hi-C (high-throughput chromatin conformation capture), a method to detect long-range chromatin interactions, allows extensive genome-wide investigation of 3D chromatin structure. However, broad application of Hi-C data have been hindered by the level of complexity in processing Hi-C data and the large size of raw sequencing data. In order to overcome these limitations, we constructed a database named 3DIV (a 3D-genome Interaction Viewer and database) that provides a list of long-range chromatin interaction partners for the queried locus with genomic and epigenomic annotations...
November 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29099269/a-meeting-at-risk-unrepaired-dsbs-go-for-broke
#8
Aude Guénolé, Gaëlle Legube
Translocations are dramatic genomic rearrangements due to aberrant rejoining of distant DNA ends that can trigger cancer onset and progression. Translocations frequently occur in genes, yet the mechanisms underlying their formation remain poorly understood. One potential mechanism involves DNA Double Strand Break mobility and juxtaposition (i.e. clustering), an event that has been intensively debated over the past decade. Using Capture Hi-C, we recently found that DSBs do in fact cluster in human nuclei but only when induced in transcriptionally active genes...
November 3, 2017: Nucleus
https://www.readbyqxmd.com/read/29094699/two-independent-modes-of-chromatin-organization-revealed-by-cohesin-removal
#9
Wibke Schwarzer, Nezar Abdennur, Anton Goloborodko, Aleksandra Pekowska, Geoffrey Fudenberg, Yann Loe-Mie, Nuno A Fonseca, Wolfgang Huber, Christian H Haering, Leonid Mirny, Francois Spitz
Imaging and chromosome conformation capture studies have revealed several layers of chromosome organization, including segregation into megabase-sized active and inactive compartments, and partitioning into sub-megabase domains (TADs). It remains unclear, however, how these layers of organization form, interact with one another and influence genome function. Here we show that deletion of the cohesin-loading factor Nipbl in mouse liver leads to a marked reorganization of chromosomal folding. TADs and associated Hi-C peaks vanish globally, even in the absence of transcriptional changes...
November 2, 2017: Nature
https://www.readbyqxmd.com/read/29089515/chromatin-interaction-networks-revealed-unique-connectivity-patterns-of-broad-h3k4me3-domains-and-super-enhancers-in-3d-chromatin
#10
Asa Thibodeau, Eladio J Márquez, Dong-Guk Shin, Paola Vera-Licona, Duygu Ucar
Broad domain promoters and super enhancers are regulatory elements that govern cell-specific functions and harbor disease-associated sequence variants. These elements are characterized by distinct epigenomic profiles, such as expanded deposition of histone marks H3K27ac for super enhancers and H3K4me3 for broad domains, however little is known about how they interact with each other and the rest of the genome in three-dimensional chromatin space. Using network theory methods, we studied chromatin interactions between broad domains and super enhancers in three ENCODE cell lines (K562, MCF7, GM12878) obtained via ChIA-PET, Hi-C, and Hi-CHIP assays...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29081791/physical-interactions-and-expression-quantitative-traits-loci-identify-regulatory-connections-for-obesity-and-type-2-diabetes-associated-snps
#11
Tayaza Fadason, Cameron Ekblad, John R Ingram, William S Schierding, Justin M O'Sullivan
The mechanisms that underlie the association between obesity and type 2 diabetes are not fully understood. Here, we investigated the role of the 3D genome organization in the pathogeneses of obesity and type-2 diabetes. We interpreted the combined and differential impacts of 196 diabetes and 390 obesity associated single nucleotide polymorphisms (SNPs) by integrating data on the genes with which they physically interact (as captured by Hi-C) and the functional [i.e., expression quantitative trait loci (eQTL)] outcomes associated with these interactions...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/29080874/-computer-methods-of-analysis-of-chromosome-contacts-in-the-cell-nucleus-based-on-sequencing-technology-data
#12
Y L Orlov, O Thierry, A G Bogomolov, A V Tsukanov, E V Kulakova, E R Galieva, A O Bragin, G Li
The study spatial chromosome structure and chromosome folding in the interphase cell nucleus is an important challenge of world science. Detection of eukaryotic genome regions that physically interact with each other could be done by modern sequencing technologies. A basic method of chromosome folding by total sequencing of contacting DNA fragments is HI-C. Long-range chromosomal interactions play an important role in gene transcription and regulation. The study of chromosome interactions, 3D (three-dimensional) genome structure and its effect on gene transcription allows revealing fundamental biological processes from a viewpoint of structural regulation and are important for cancer research...
October 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/29077530/recent-evidence-that-tads-and-chromatin-loops-are-dynamic-structures
#13
Anders S Hansen, Claudia Cattoglio, Xavier Darzacq, Robert Tjian
Mammalian genomes are folded into spatial domains, which regulate gene expression by modulating enhancer-promoter contacts. Here, we review recent studies on the structure and function of Topologically Associating Domains (TADs) and chromatin loops. We discuss how loop extrusion models can explain TAD formation and evidence that TADs are formed by the ring-shaped protein complex, cohesin, and that TAD boundaries are established by the DNA-binding protein, CTCF. We discuss our recent genomic, biochemical and single-molecule imaging studies on CTCF and cohesin, which suggest that TADs and chromatin loops are dynamic structures...
October 27, 2017: Nucleus
https://www.readbyqxmd.com/read/29076094/chromosome-conformation-capture-3c-and-higher-with-erythroid-samples
#14
Ivan Krivega, Ann Dean
Chromosome conformation capture (3C) allows for the determination of the proximity in nuclei of DNA sequences that are linearly distant from one another in the genome. Proximity that is above that expected from random interaction provides evidence for potential long-range functional interactions such as between enhancers and their target genes. Many controls are required to convincingly demonstrate increased frequency of interaction between sequences and stringent functional tests must also be applied. Here, we present methodology suitable for 3C experiments that can also be applied as the basis for related 4C, 5C, and Hi-C approaches...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29070071/mcenhancer-predicting-gene-expression-via-semi-supervised-assignment-of-enhancers-to-target-genes
#15
Dina Hafez, Aslihan Karabacak, Sabrina Krueger, Yih-Chii Hwang, Li-San Wang, Robert P Zinzen, Uwe Ohler
Transcriptional enhancers regulate spatio-temporal gene expression. While genomic assays can identify putative enhancers en masse, assigning target genes is a complex challenge. We devised a machine learning approach, McEnhancer, which links target genes to putative enhancers via a semi-supervised learning algorithm that predicts gene expression patterns based on enriched sequence features. Predicted expression patterns were 73-98% accurate, predicted assignments showed strong Hi-C interaction enrichment, enhancer-associated histone modifications were evident, and known functional motifs were recovered...
October 26, 2017: Genome Biology
https://www.readbyqxmd.com/read/29066944/a-polymer-physics-investigation-of-the-architecture-of-the-murine-orthologue-of-the-7q11-23-human-locus
#16
REVIEW
Andrea M Chiariello, Andrea Esposito, Carlo Annunziatella, Simona Bianco, Luca Fiorillo, Antonella Prisco, Mario Nicodemi
In the last decade, the developments of novel technologies, such as Hi-C or GAM methods, allowed to discover that chromosomes in the nucleus of mammalian cells have a complex spatial organization, encompassing the functional contacts between genes and regulators. In this work, we review recent progresses in chromosome modeling based on polymer physics to understand chromatin structure and folding mechanisms. As an example, we derive in mouse embryonic stem cells the full 3D structure of the Bmp7 locus, a genomic region that plays a key role in osteoblastic differentiation...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29058599/evidence-of-reduced-recombination-rate-in-human-regulatory-domains
#17
Yaping Liu, Abhishek Sarkar, Pouya Kheradpour, Jason Ernst, Manolis Kellis
BACKGROUND: Recombination rate is non-uniformly distributed across the human genome. The variation of recombination rate at both fine and large scales cannot be fully explained by DNA sequences alone. Epigenetic factors, particularly DNA methylation, have recently been proposed to influence the variation in recombination rate. RESULTS: We study the relationship between recombination rate and gene regulatory domains, defined by a gene and its linked control elements...
October 20, 2017: Genome Biology
https://www.readbyqxmd.com/read/29053968/multiscale-3d-genome-rewiring-during-mouse-neural-development
#18
Boyan Bonev, Netta Mendelson Cohen, Quentin Szabo, Lauriane Fritsch, Giorgio L Papadopoulos, Yaniv Lubling, Xiaole Xu, Xiaodan Lv, Jean-Philippe Hugnot, Amos Tanay, Giacomo Cavalli
Chromosome conformation capture technologies have revealed important insights into genome folding. Yet, how spatial genome architecture is related to gene expression and cell fate remains unclear. We comprehensively mapped 3D chromatin organization during mouse neural differentiation in vitro and in vivo, generating the highest-resolution Hi-C maps available to date. We found that transcription is correlated with chromatin insulation and long-range interactions, but dCas9-mediated activation is insufficient for creating TAD boundaries de novo...
October 19, 2017: Cell
https://www.readbyqxmd.com/read/29048533/parallel-sequencing-lives-or-what-makes-large-sequencing-projects-successful
#19
Javier Quilez, Enrique Vidal, François Le Dily, François Serra, Yasmina Cuartero, Ralph Stadhouders, Thomas Graf, Marc A Marti-Renom, Miguel Beato, Guillaume Filion
T47D_rep2 and b1913e6c1_51720e9cf were two Hi-C samples. They were born and processed at the same time, yet their fates were very different. The life of b1913e6c1_51720e9cf was simple and fruitful, while that of T47D_rep2 was full of accidents and sorrow. At the heart of these differences lies the fact that b1913e6c1_51720e9cf was born under a lab culture of Documentation, Automation, Traceability, Autonomy and compliance with the FAIR Principles. Their lives are a lesson for those who wish to embark on the journey of managing high throughput sequencing data...
October 18, 2017: GigaScience
https://www.readbyqxmd.com/read/29048467/identification-of-copy-number-variations-and-translocations-in-cancer-cells-from-hi-c-data
#20
Abhijit Chakraborty, Ferhat Ay
Motivation: Eukaryotic chromosomes adapt a complex and highly dynamic three-dimensional (3D) structure, which profoundly affects different cellular functions and outcomes including changes in epigenetic landscape and in gene expression. Making the scenario even more complex, cancer cells harbor chromosomal abnormalities (e.g., copy number variations (CNVs) and translocations) altering their genomes both at the sequence level and at the level of 3D organization. High-throughput chromosome conformation capture techniques (e...
October 18, 2017: Bioinformatics
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