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https://www.readbyqxmd.com/read/28742097/mrtadfinder-a-network-modularity-based-approach-to-identify-topologically-associating-domains-in-multiple-resolutions
#1
Koon-Kiu Yan, Shaoke Lou, Mark Gerstein
Genome-wide proximity ligation based assays such as Hi-C have revealed that eukaryotic genomes are organized into structural units called topologically associating domains (TADs). From a visual examination of the chromosomal contact map, however, it is clear that the organization of the domains is not simple or obvious. Instead, TADs exhibit various length scales and, in many cases, a nested arrangement. Here, by exploiting the resemblance between TADs in a chromosomal contact map and densely connected modules in a network, we formulate TAD identification as a network optimization problem and propose an algorithm, MrTADFinder, to identify TADs from intra-chromosomal contact maps...
July 24, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28723903/automatic-analysis-and-3d-modelling-of-hi-c-data-using-tadbit-reveals-structural-features-of-the-fly-chromatin-colors
#2
François Serra, Davide Baù, Mike Goodstadt, David Castillo, Guillaume Filion, Marc A Marti-Renom
The sequence of a genome is insufficient to understand all genomic processes carried out in the cell nucleus. To achieve this, the knowledge of its three-dimensional architecture is necessary. Advances in genomic technologies and the development of new analytical methods, such as Chromosome Conformation Capture (3C) and its derivatives, provide unprecedented insights in the spatial organization of genomes. Here we present TADbit, a computational framework to analyze and model the chromatin fiber in three dimensions...
July 19, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28720171/pacbio-assembly-of-a-plasmodium-knowlesi-genome-sequence-with-hi-c-correction-and-manual-annotation-of-the-sicavar-gene-family
#3
S A Lapp, J A Geraldo, J-T Chien, F Ay, S B Pakala, G Batugedara, J Humphrey, J D DeBARRY, K G Le Roch, M R Galinski, J C Kissinger
Plasmodium knowlesi has risen in importance as a zoonotic parasite that has been causing regular episodes of malaria throughout South East Asia. The P. knowlesi genome sequence generated in 2008 highlighted and confirmed many similarities and differences in Plasmodium species, including a global view of several multigene families, such as the large SICAvar multigene family encoding the variant antigens known as the schizont-infected cell agglutination proteins. However, repetitive DNA sequences are the bane of any genome project, and this and other Plasmodium genome projects have not been immune to the gaps, rearrangements and other pitfalls created by these genomic features...
July 19, 2017: Parasitology
https://www.readbyqxmd.com/read/28709003/3d-chromatin-structures-of-mature-gametes-and-structural-reprogramming-during-mammalian-embryogenesis
#4
Yuwen Ke, Yanan Xu, Xuepeng Chen, Songjie Feng, Zhenbo Liu, Yaoyu Sun, Xuelong Yao, Fangzhen Li, Wei Zhu, Lei Gao, Haojie Chen, Zhenhai Du, Wei Xie, Xiaocui Xu, Xingxu Huang, Jiang Liu
High-order chromatin structure plays important roles in gene expression regulation. Knowledge of the dynamics of 3D chromatin structures during mammalian embryo development remains limited. We report the 3D chromatin architecture of mouse gametes and early embryos using an optimized Hi-C method with low-cell samples. We find that mature oocytes at the metaphase II stage do not have topologically associated domains (TADs). In sperm, extra-long-range interactions (>4 Mb) and interchromosomal interactions occur frequently...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28708563/evolving-spatial-clusters-of-genomic-regions-from-high-throughput-chromatin-conformation-capture-data
#5
Xiangtao Li, Shijing Ma, Ka-Chun Wong
High-throughput chromosome-conformation-capture (Hi-C) methods have revealed a multitude of structural insights into interphase chromosomes. In this paper, we elucidate the spatial clusters of genomic regions from Hi-C contact maps by formulating the underlying problem as a global optimization problem. Given its nonconvex objective and nonnegativity constraints, we implement several evolutionary algorithms and compare their performance with non-negative matrix factorization, revealing novel insights into the problem...
July 11, 2017: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/28703188/allelic-reprogramming-of-3d-chromatin-architecture-during-early-mammalian-development
#6
Zhenhai Du, Hui Zheng, Bo Huang, Rui Ma, Jingyi Wu, Xianglin Zhang, Jing He, Yunlong Xiang, Qiujun Wang, Yuanyuan Li, Jing Ma, Xu Zhang, Ke Zhang, Yang Wang, Michael Q Zhang, Juntao Gao, Jesse R Dixon, Xiaowo Wang, Jianyang Zeng, Wei Xie
In mammals, chromatin organization undergoes drastic reprogramming after fertilization. However, the three-dimensional structure of chromatin and its reprogramming in preimplantation development remain poorly understood. Here, by developing a low-input Hi-C (genome-wide chromosome conformation capture) approach, we examined the reprogramming of chromatin organization during early development in mice. We found that oocytes in metaphase II show homogeneous chromatin folding that lacks detectable topologically associating domains (TADs) and chromatin compartments...
July 12, 2017: Nature
https://www.readbyqxmd.com/read/28701198/scaffolding-of-long-read-assemblies-using-long-range-contact-information
#7
Jay Ghurye, Mihai Pop, Sergey Koren, Derek Bickhart, Chen-Shan Chin
BACKGROUND: Long read technologies have revolutionized de novo genome assembly by generating contigs orders of magnitude longer than that of short read assemblies. Although assembly contiguity has increased, it usually does not reconstruct a full chromosome or an arm of the chromosome, resulting in an unfinished chromosome level assembly. To increase the contiguity of the assembly to the chromosome level, different strategies are used which exploit long range contact information between chromosomes in the genome...
July 12, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28682332/cell-cycle-dynamics-of-chromosomal-organization-at-single-cell-resolution
#8
Takashi Nagano, Yaniv Lubling, Csilla Várnai, Carmel Dudley, Wing Leung, Yael Baran, Netta Mendelson Cohen, Steven Wingett, Peter Fraser, Amos Tanay
Chromosomes in proliferating metazoan cells undergo marked structural metamorphoses every cell cycle, alternating between highly condensed mitotic structures that facilitate chromosome segregation, and decondensed interphase structures that accommodate transcription, gene silencing and DNA replication. Here we use single-cell Hi-C (high-resolution chromosome conformation capture) analysis to study chromosome conformations in thousands of individual cells, and discover a continuum of cis-interaction profiles that finely position individual cells along the cell cycle...
July 5, 2017: Nature
https://www.readbyqxmd.com/read/28663546/inherited-determinants-of-early-recurrent-somatic-mutations-in-prostate-cancer
#9
Alessandro Romanel, Sonia Garritano, Blerta Stringa, Mirjam Blattner, Davide Dalfovo, Dimple Chakravarty, David Soong, Kellie A Cotter, Gianluca Petris, Priyanka Dhingra, Paola Gasperini, Anna Cereseto, Olivier Elemento, Andrea Sboner, Ekta Khurana, Alberto Inga, Mark A Rubin, Francesca Demichelis
Prostate cancer is a highly heritable molecularly and clinically heterogeneous disease. To discover germline events involved in prostate cancer predisposition, we develop a computational approach to nominate heritable facilitators of somatic genomic events in the context of the androgen receptor signaling. Here, we use a ranking score and benign prostate transcriptomes to identify a non-coding polymorphic regulatory element at 7p14.3 that associates with DNA repair and hormone-regulated transcript levels and with an early recurrent prostate cancer-specific somatic mutation in the Speckle-Type POZ protein (SPOP) gene...
June 29, 2017: Nature Communications
https://www.readbyqxmd.com/read/28655341/hi-c-as-a-tool-for-precise-detection-and-characterisation-of-chromosomal-rearrangements-and-copy-number-variation-in-human-tumours
#10
Louise Harewood, Kamal Kishore, Matthew D Eldridge, Steven Wingett, Danita Pearson, Stefan Schoenfelder, V Peter Collins, Peter Fraser
Chromosomal rearrangements occur constitutionally in the general population and somatically in the majority of cancers. Detection of balanced rearrangements, such as reciprocal translocations and inversions, is troublesome, which is particularly detrimental in oncology where rearrangements play diagnostic and prognostic roles. Here we describe the use of Hi-C as a tool for detection of both balanced and unbalanced chromosomal rearrangements in primary human tumour samples, with the potential to define chromosome breakpoints to bp resolution...
June 27, 2017: Genome Biology
https://www.readbyqxmd.com/read/28623585/in-situ-hi-c-library-preparation-for-plants-to-study-their-three-dimensional-chromatin-interactions-on-a-genome-wide-scale
#11
Chang Liu
The spatial organization of the genome in the nucleus is critical for many cellular processes. It has been broadly accepted that the packing of chromatin inside the nucleus is not random, but structured at several hierarchical levels. The Hi-C method combines Chromatin Conformation Capture and high-throughput sequencing, which allows interrogating genome-wide chromatin interactions. Depending on the sequencing depth, chromatin packing patterns derived from Hi-C experiments can be viewed on a chromosomal scale or at a local genic level...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28604728/identification-of-19-new-risk-loci-and-potential-regulatory-mechanisms-influencing-susceptibility-to-testicular-germ-cell-tumor
#12
Kevin Litchfield, Max Levy, Giulia Orlando, Chey Loveday, Philip J Law, Gabriele Migliorini, Amy Holroyd, Peter Broderick, Robert Karlsson, Trine B Haugen, Wenche Kristiansen, Jérémie Nsengimana, Kerry Fenwick, Ioannis Assiotis, ZSofia Kote-Jarai, Alison M Dunning, Kenneth Muir, Julian Peto, Rosalind Eeles, Douglas F Easton, Darshna Dudakia, Nick Orr, Nora Pashayan, D Timothy Bishop, Alison Reid, Robert A Huddart, Janet Shipley, Tom Grotmol, Fredrik Wiklund, Richard S Houlston, Clare Turnbull
Genome-wide association studies (GWAS) have transformed understanding of susceptibility to testicular germ cell tumors (TGCTs), but much of the heritability remains unexplained. Here we report a new GWAS, a meta-analysis with previous GWAS and a replication series, totaling 7,319 TGCT cases and 23,082 controls. We identify 19 new TGCT risk loci, roughly doubling the number of known TGCT risk loci to 44. By performing in situ Hi-C in TGCT cells, we provide evidence for a network of physical interactions among all 44 TGCT risk SNPs and candidate causal genes...
July 2017: Nature Genetics
https://www.readbyqxmd.com/read/28604723/fish-ing-for-captured-contacts-towards-reconciling-fish-and-3c
#13
Geoffrey Fudenberg, Maxim Imakaev
Chromosome conformation capture (3C) and fluorescence in situ hybridization (FISH) are two widely used technologies that provide distinct readouts of 3D chromosome organization. While both technologies can assay locus-specific organization, how to integrate views from 3C, or genome-wide Hi-C, and FISH is far from solved. Contact frequency, measured by Hi-C, and spatial distance, measured by FISH, are often assumed to quantify the same phenomena and used interchangeably. Here, however, we demonstrate that contact frequency is distinct from average spatial distance, both in polymer simulations and in experimental data...
July 2017: Nature Methods
https://www.readbyqxmd.com/read/28604721/comparison-of-computational-methods-for-hi-c-data-analysis
#14
Mattia Forcato, Chiara Nicoletti, Koustav Pal, Carmen Maria Livi, Francesco Ferrari, Silvio Bicciato
Hi-C is a genome-wide sequencing technique used to investigate 3D chromatin conformation inside the nucleus. Computational methods are required to analyze Hi-C data and identify chromatin interactions and topologically associating domains (TADs) from genome-wide contact probability maps. We quantitatively compared the performance of 13 algorithms in their analyses of Hi-C data from six landmark studies and simulations. This comparison revealed differences in the performance of methods for chromatin interaction identification, but more comparable results for TAD detection between algorithms...
July 2017: Nature Methods
https://www.readbyqxmd.com/read/28588240/structural-modeling-of-chromatin-integrates-genome-features-and-reveals-chromosome-folding-principle
#15
Wen Jun Xie, Luming Meng, Sirui Liu, Ling Zhang, Xiaoxia Cai, Yi Qin Gao
How chromosomes fold into 3D structures and how genome functions are affected or even controlled by their spatial organization remain challenging questions. Hi-C experiment has provided important structural insights for chromosome, and Hi-C data are used here to construct the 3D chromatin structure which are characterized by two spatially segregated chromatin compartments A and B. By mapping a plethora of genome features onto the constructed 3D chromatin model, we show vividly the close connection between genome properties and the spatial organization of chromatin...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28583068/lncrna-screen-an-interactive-platform-for-computationally-screening-long-non-coding-rnas-in-large-genomics-datasets
#16
Yixiao Gong, Hsuan-Ting Huang, Yu Liang, Thomas Trimarchi, Iannis Aifantis, Aristotelis Tsirigos
BACKGROUND: Long non-coding RNAs (lncRNAs) have emerged as a class of factors that are important for regulating development and cancer. Computational prediction of lncRNAs from ultra-deep RNA sequencing has been successful in identifying candidate lncRNAs. However, the complexity of handling and integrating different types of genomics data poses significant challenges to experimental laboratories that lack extensive genomics expertise. RESULT: To address this issue, we have developed lncRNA-screen, a comprehensive pipeline for computationally screening putative lncRNA transcripts over large multimodal datasets...
June 5, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28582503/hugin-hi-c-unifying-genomic-interrogator
#17
Joshua S Martin, Zheng Xu, Alex P Reiner, Karen L Mohlke, Patrick Sullivan, Bing Ren, Ming Hu, Yun Li
Motivation: High throughput chromatin conformation capture (3C) technologies, such as Hi-C and ChIA-PET, have the potential to elucidate the functional roles of non-coding variants. However, most of published genome-wide unbiased chromatin organization studies have used cultured cell lines, limiting their generalizability. Results: We developed a web browser, HUGIn, to visualize Hi-C data generated from 21 human primary tissues and cell lines. HUGIn enables assessment of chromatin contacts both constitutive across and specific to tissue(s) and/or cell line(s) at any genomic loci, including GWAS SNPs, eQTLs and cis-regulatory elements, facilitating the understanding of both GWAS and eQTLs results and functional genomics data...
June 5, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28575119/nucleolus-association-of-chromosomal-domains-is-largely-maintained-in-cellular-senescence-despite-massive-nuclear-reorganisation
#18
Stefan Dillinger, Tobias Straub, Attila Németh
Mammalian chromosomes are organized in structural and functional domains of 0.1-10 Mb, which are characterized by high self-association frequencies in the nuclear space and different contact probabilities with nuclear sub-compartments. They exhibit distinct chromatin modification patterns, gene expression levels and replication timing. Recently, nucleolus-associated chromosomal domains (NADs) have been discovered, yet their precise genomic organization and dynamics are still largely unknown. Here, we use nucleolus genomics and single-cell experiments to address these questions in human embryonic fibroblasts during replicative senescence...
2017: PloS One
https://www.readbyqxmd.com/read/28573677/physical-properties-of-the-chromosomes-and-implications-for-development
#19
REVIEW
Takeshi Sugawara, Akatsuki Kimura
Remarkable progress has been made in understanding chromosome structures inside the cell nucleus. Recent advances in Hi-C technologies enable the detection of genome-wide chromatin interactions, providing insight into three-dimensional (3D) genome organization. Advancements in the spatial and temporal resolutions of imaging as well as in molecular biological techniques allow the tracking of specific chromosomal loci, improving our understanding of chromosome movements. From these data, we are beginning to understand how the intra-nuclear locations of chromatin loci and the 3D genome structure change during development and differentiation...
June 2, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/28544514/dynamic-enhancer-function-in-the-chromatin-context
#20
REVIEW
Ido Goldstein, Gordon L Hager
Enhancers serve as critical regulatory elements in higher eukaryotic cells. The characterization of enhancer function has evolved primarily from genome-wide methodologies, including chromatin immunoprecipitation (ChIP-seq), DNase-I hypersensitivity (DNase-seq), digital genomic footprinting (DGF), and the chromosome conformation capture techniques (3C, 4C, and Hi-C). These population-based assays average signals across millions of cells and lead to enhancer models characterized by static and sequential binding...
May 22, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
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