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https://www.readbyqxmd.com/read/29901812/galaxy-hicexplorer-a-web-server-for-reproducible-hi-c-data-analysis-quality-control-and-visualization
#1
Joachim Wolff, Vivek Bhardwaj, Stephan Nothjunge, Gautier Richard, Gina Renschler, Ralf Gilsbach, Thomas Manke, Rolf Backofen, Fidel Ramírez, Björn A Grüning
Galaxy HiCExplorer is a web server that facilitates the study of the 3D conformation of chromatin by allowing Hi-C data processing, analysis and visualization. With the Galaxy HiCExplorer web server, users with little bioinformatic background can perform every step of the analysis in one workflow: mapping of the raw sequence data, creation of Hi-C contact matrices, quality assessment, correction of contact matrices and identification of topological associated domains (TADs) and A/B compartments. Users can create publication ready plots of the contact matrix, A/B compartments, and TADs on a selected genomic locus, along with additional information like gene tracks or ChIP-seq signals...
June 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29900125/genome-wide-analysis-of-interchromosomal-interaction-probabilities-reveals-chained-translocations-and-overrepresentation-of-translocation-breakpoints-in-genes-in-a-cutaneous-t-cell-lymphoma-cell-line
#2
Anne Steininger, Grit Ebert, Benjamin V Becker, Chalid Assaf, Markus Möbs, Christian A Schmidt, Piotr Grabarczyk, Lars R Jensen, Grzegorz K Przybylski, Matthias Port, Andreas W Kuss, Reinhard Ullmann
In classical models of tumorigenesis, the accumulation of tumor promoting chromosomal aberrations is described as a gradual process. Next-generation sequencing-based methods have recently revealed complex patterns of chromosomal aberrations, which are beyond explanation by these classical models of karyotypic evolution of tumor genomes. Thus, the term chromothripsis has been introduced to describe a phenomenon, where temporarily and spatially confined genomic instability results in dramatic chromosomal rearrangements limited to segments of one or a few chromosomes...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29848293/improved-accuracy-assessment-for-3d-genome-reconstructions
#3
Mark R Segal, Henrik L Bengtsson
BACKGROUND: Three dimensional (3D) genome spatial organization is critical for numerous cellular functions, including transcription, while certain conformation-driven structural alterations are frequently oncogenic. Genome conformation had been difficult to elucidate but the advent chromatin conformation capture assays, notably Hi-C, has transformed understanding of chromatin architecture and yielded numerous biological insights. Although most of these findings have flowed from analysis of proximity data produced by these assays, added value in generating 3D reconstructions has been demonstrated, deriving, in part, from superposing genomic features on the reconstruction...
May 30, 2018: BMC Bioinformatics
https://www.readbyqxmd.com/read/29804679/single-nucleus-hi-c-of-mammalian-oocytes-and-zygotes
#4
Johanna Gassler, Ilya M Flyamer, Kikuë Tachibana
The 3D folding of the genome is linked to essential nuclear processes including gene expression, DNA repair, and replication. Chromatin conformation capture assays such as Hi-C are providing unprecedented insights into higher-order chromatin structure. Bulk Hi-C of millions of cells enables detection of average chromatin features at high resolution but is challenging to apply to rare cell types. This chapter describes our recently developed single-nucleus Hi-C (snHi-C) approach for detection of chromatin contacts in single nuclei of murine oocytes and one-cell embryos (zygotes)...
2018: Methods in Cell Biology
https://www.readbyqxmd.com/read/29800273/peakc-a-flexible-non-parametric-peak-calling-package-for-4c-and-capture-c-data
#5
Geert Geeven, Hans Teunissen, Wouter de Laat, Elzo de Wit
It is becoming increasingly clear that chromosome organization plays an important role in gene regulation. High-resolution methods such as 4C, Capture-C and promoter capture Hi-C (PCHiC) enable the study of chromatin loops such as those formed between promoters and enhancers or CTCF/cohesin binding sites. An important aspect of 4C/Capture-C/PCHiC analyses is the reliable identification of chromatin loops, preferably not based on visual inspection of a DNA contact profile, but on reproducible statistical analysis that robustly scores interaction peaks in the non-uniform contact background...
May 25, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29796744/3d-genome-and-its-disorganization-in-diseases
#6
REVIEW
Ruifeng Li, Yuting Liu, Yingping Hou, Jingbo Gan, Pengze Wu, Cheng Li
The chromosomes in eukaryotic cells are highly folded and organized to form dynamic three-dimensional (3D) structures. In recent years, many technologies including chromosome conformation capture (3C) and 3C-based technologies (Hi-C, ChIA-PET) have been developed to investigate the 3D structure of chromosomes. These technologies are enabling research on how gene regulatory events are affected by the 3D genome structure, which is increasingly implicated in the regulation of gene expression and cellular functions...
May 23, 2018: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/29787433/investigation-of-spatial-organization-of-chromosome-territories-in-chromosome-exchange-aberrations-after-ionizing-radiation-exposure
#7
Adayabalam S Balajee, Jacob T Sanders, Rosela Golloshi, Igor Shuryak, Rachel Patton McCord, Nicholas Dainiak
Higher-order organization of the human genome is well established with chromosomes occupying distinct domains or territories in the interphase nucleus. Spatial organization of chromosome territories in the interphase nucleus occurs in a cell-type-specific manner. Since both stable and unstable aberrations induced by ionizing radiation involve the exchange of material between two or more chromosomes, this study investigated the role of spatial organization of chromosome domains in ionizing-radiation-induced chromosome translocation events...
July 2018: Health Physics
https://www.readbyqxmd.com/read/29772275/5c-id-increased-resolution-chromosome-conformation-capture-carbon-copy-with-in-situ-3c-and-double-alternating-primer-design
#8
Ji Hun Kim, Katelyn R Titus, Wanfeng Gong, Jonathan A Beagan, Zhendong Cao, Jennifer E Phillips-Cremins
Mammalian genomes are folded in a hierarchy of compartments, topologically associating domains (TADs), subTADs, and looping interactions. Currently, there is a great need to evaluate the link between chromatin topology and genome function across many biological conditions and genetic perturbations. Hi-C can generate genome-wide maps of looping interactions but is intractable for high-throughput comparison of loops across multiple conditions due to the enormous number of reads (>6 Billion) required per library...
May 14, 2018: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/29771388/gwas4d-multidimensional-analysis-of-context-specific-regulatory-variant-for-human-complex-diseases-and-traits
#9
Dandan Huang, Xianfu Yi, Shijie Zhang, Zhanye Zheng, Panwen Wang, Chenghao Xuan, Pak Chung Sham, Junwen Wang, Mulin Jun Li
Genome-wide association studies have generated over thousands of susceptibility loci for many human complex traits, and yet for most of these associations the true causal variants remain unknown. Tissue/cell type-specific prediction and prioritization of non-coding regulatory variants will facilitate the identification of causal variants and underlying pathogenic mechanisms for particular complex diseases and traits. By leveraging recent large-scale functional genomics/epigenomics data, we develop an intuitive web server, GWAS4D (http://mulinlab...
May 16, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29767669/identification-of-mutations-in-patients-with-acquired-pure-red-cell-aplasia
#10
Xinchao Zhang, Yi Shi, Lingjun Song, Chang Shen, Qi Cai, Zhou Zhang, Jun Wu, Guohui Fu, Weiwei Shen
Idiopathic acquired pure red cell aplasia (PRCA) is a rare, autoimmune-related disease. This study aimed to describe the previously unidentified DNA alterations associated with PRCA. Here, next generation sequencing using a panel containing 295 critical genes was applied to detect potentially pathogenic mutations in four patients with PRCA. A total of 529 mutations were identified and further classified into three categories, namely, uncertain (n = 25), likely benign (n = 20) and benign (n = 484) mutations, based on the American College of Medical Genetics and Genomics (ACMG) 2015 guidelines and ClinVar database...
May 15, 2018: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29755580/finding-local-genome-rearrangements
#11
Pijus Simonaitis, Krister M Swenson
Background: The double cut and join (DCJ) model of genome rearrangement is well studied due to its mathematical simplicity and power to account for the many events that transform gene order. These studies have mostly been devoted to the understanding of minimum length scenarios transforming one genome into another. In this paper we search instead for rearrangement scenarios that minimize the number of rearrangements whose breakpoints are unlikely due to some biological criteria. One such criterion has recently become accessible due to the advent of the Hi-C experiment, facilitating the study of 3D spacial distance between breakpoint regions...
2018: Algorithms for Molecular Biology: AMB
https://www.readbyqxmd.com/read/29745835/graphteams-a-method-for-discovering-spatial-gene-clusters-in-hi-c-sequencing-data
#12
Tizian Schulz, Jens Stoye, Daniel Doerr
BACKGROUND: Hi-C sequencing offers novel, cost-effective means to study the spatial conformation of chromosomes. We use data obtained from Hi-C experiments to provide new evidence for the existence of spatial gene clusters. These are sets of genes with associated functionality that exhibit close proximity to each other in the spatial conformation of chromosomes across several related species. RESULTS: We present the first gene cluster model capable of handling spatial data...
May 8, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29735606/allele-specific-control-of-replication-timing-and-genome-organization-during-development
#13
Juan Carlos Rivera-Mulia, Andrew Dimond, Daniel Vera, Claudia Trevilla-Garcia, Takayo Sasaki, Jared Zimmerman, Catherine Dupont, Joost Gribnau, Peter Fraser, David M Gilbert
DNA replication occurs in a defined temporal order known as the replication-timing (RT) program. RT is regulated during development in discrete chromosomal units, coordinated with transcriptional activity and 3D genome organization. Here, we derived distinct cell types from F1 hybrid musculus × castaneus mouse crosses and exploited the high single-nucleotide polymorphism (SNP) density to characterize allelic differences in RT (Repli-seq), genome organization (Hi-C and promoter-capture Hi-C), gene expression (total nuclear RNA-seq), and chromatin accessibility (ATAC-seq)...
June 2018: Genome Research
https://www.readbyqxmd.com/read/29728444/emerging-evidence-of-chromosome-folding-by-loop-extrusion
#14
Geoffrey Fudenberg, Nezar Abdennur, Maxim Imakaev, Anton Goloborodko, Leonid A Mirny
Chromosome organization poses a remarkable physical problem with many biological consequences: How can molecular interactions between proteins at the nanometer scale organize micron-long chromatinized DNA molecules, insulating or facilitating interactions between specific genomic elements? The mechanism of active loop extrusion holds great promise for explaining interphase and mitotic chromosome folding, yet remains difficult to assay directly. We discuss predictions from our polymer models of loop extrusion with barrier elements and review recent experimental studies that provide strong support for loop extrusion, focusing on perturbations to CTCF and cohesin assayed via Hi-C in interphase...
May 4, 2018: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/29723572/iteratively-improving-hi-c-experiments-one-step-at-a-time
#15
Rosela Golloshi, Jacob Sanders, Rachel Patton McCord
The 3D organization of eukaryotic chromosomes affects key processes such as gene expression, DNA replication, cell division, and response to DNA damage. The genome-wide chromosome conformation capture (Hi-C) approach can characterize the landscape of 3D genome organization by measuring interaction frequencies between all genomic regions. Hi-C protocol improvements and rapid advances in DNA sequencing power have made Hi-C useful to study diverse biological systems, not only to elucidate the role of 3D genome structure in proper cellular function, but also to characterize genomic rearrangements, assemble new genomes, and consider chromatin interactions as potential biomarkers for diseases...
April 30, 2018: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/29717274/detecting-epistasis-within-chromatin-regulatory-circuitry-reveals-cand2-as-a-novel-susceptibility-gene-for-obesity
#16
Shan-Shan Dong, Shi Yao, Yi-Xiao Chen, Yan Guo, Yu-Jie Zhang, Hui-Min Niu, Ruo-Han Hao, Hui Shen, Qing Tian, Hong-Wen Deng, Tie-Lin Yang
BACKGROUND: Genome-wide association studies have identified many susceptibility loci for obesity. However, missing heritability problem is still challenging and ignorance of genetic interactions is believed to be an important cause. Current methods for detecting interactions usually do not consider regulatory elements in non-coding regions. Interaction analyses within chromatin regulatory circuitry may identify new susceptibility loci. METHODS: We developed a pipeline named interaction analyses within chromatin regulatory circuitry (IACRC), to identify genetic interactions impacting body mass index (BMI)...
May 1, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29706548/the-energetics-and-physiological-impact-of-cohesin-extrusion
#17
Laura Vian, Aleksandra Pękowska, Suhas S P Rao, Kyong-Rim Kieffer-Kwon, Seolkyoung Jung, Laura Baranello, Su-Chen Huang, Laila El Khattabi, Marei Dose, Nathanael Pruett, Adrian L Sanborn, Andres Canela, Yaakov Maman, Anna Oksanen, Wolfgang Resch, Xingwang Li, Byoungkoo Lee, Alexander L Kovalchuk, Zhonghui Tang, Steevenson Nelson, Michele Di Pierro, Ryan R Cheng, Ido Machol, Brian Glenn St Hilaire, Neva C Durand, Muhammad S Shamim, Elena K Stamenova, José N Onuchic, Yijun Ruan, Andre Nussenzweig, David Levens, Erez Lieberman Aiden, Rafael Casellas
Cohesin extrusion is thought to play a central role in establishing the architecture of mammalian genomes. However, extrusion has not been visualized in vivo, and thus, its functional impact and energetics are unknown. Using ultra-deep Hi-C, we show that loop domains form by a process that requires cohesin ATPases. Once formed, however, loops and compartments are maintained for hours without energy input. Strikingly, without ATP, we observe the emergence of hundreds of CTCF-independent loops that link regulatory DNA...
May 17, 2018: Cell
https://www.readbyqxmd.com/read/29706538/hmgb2-loss-upon-senescence-entry-disrupts-genomic-organization-and-induces-ctcf-clustering-across-cell-types
#18
Anne Zirkel, Milos Nikolic, Konstantinos Sofiadis, Jan-Philipp Mallm, Chris A Brackley, Henrike Gothe, Oliver Drechsel, Christian Becker, Janine Altmüller, Natasa Josipovic, Theodore Georgomanolis, Lilija Brant, Julia Franzen, Mirjam Koker, Eduardo G Gusmao, Ivan G Costa, Roland T Ullrich, Wolfgang Wagner, Vassilis Roukos, Peter Nürnberg, Davide Marenduzzo, Karsten Rippe, Argyris Papantonis
Processes like cellular senescence are characterized by complex events giving rise to heterogeneous cell populations. However, the early molecular events driving this cascade remain elusive. We hypothesized that senescence entry is triggered by an early disruption of the cells' three-dimensional (3D) genome organization. To test this, we combined Hi-C, single-cell and population transcriptomics, imaging, and in silico modeling of three distinct cells types entering senescence. Genes involved in DNA conformation maintenance are suppressed upon senescence entry across all cell types...
April 20, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29700484/computational-3d-genome-modeling-using-chrom3d
#19
Jonas Paulsen, Tharvesh Moideen Liyakat Ali, Philippe Collas
Chrom3D is a computational platform for 3D genome modeling that simulates the spatial positioning of chromosome domains relative to each other and relative to the nuclear periphery. In Chrom3D, chromosomes are modeled as chains of contiguous beads, in which each bead represents a genomic domain. In this protocol, a bead represents a topologically associated domain (TAD) mapped from ensemble Hi-C data. Chrom3D takes as input data significant pairwise TAD-TAD interactions determined from a Hi-C contact matrix, and TAD interactions with the nuclear periphery, determined by ChIP-sequencing of nuclear lamins to define lamina-associated domains (LADs)...
May 2018: Nature Protocols
https://www.readbyqxmd.com/read/29700467/digestion-ligation-only-hi-c-is-an-efficient-and-cost-effective-method-for-chromosome-conformation-capture
#20
Da Lin, Ping Hong, Siheng Zhang, Weize Xu, Muhammad Jamal, Keji Yan, Yingying Lei, Liang Li, Yijun Ruan, Zhen F Fu, Guoliang Li, Gang Cao
Chromosome conformation capture (3C) technologies can be used to investigate 3D genomic structures. However, high background noise, high costs, and a lack of straightforward noise evaluation in current methods impede the advancement of 3D genomic research. Here we developed a simple digestion-ligation-only Hi-C (DLO Hi-C) technology to explore the 3D landscape of the genome. This method requires only two rounds of digestion and ligation, without the need for biotin labeling and pulldown. Non-ligated DNA was efficiently removed in a cost-effective step by purifying specific linker-ligated DNA fragments...
April 26, 2018: Nature Genetics
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