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3D genomics

Rongrong Zhang, Ming Hu, Yu Michael Zhu, Zhaohui Steve Qin, Ke Deng, Jun Liu
The recently developed Hi-C technology enables a genome-wide view of chromosome spatial organizations, and has shed deep insights into genome structure and genome function. However, multiple sources of uncertainties make downstream data analysis and interpretation challenging. Specifically, statistical models for inferring three-dimensional (3D) chromosomal structure from Hi-C data are far from their maturity. Most existing methods are highly over-parameterized, lacking clear interpretations, and sensitive to outliers...
August 15, 2018: IEEE/ACM Transactions on Computational Biology and Bioinformatics
Renee S Arias, Victor S Sobolev, Alicia N Massa, Valerie A Orner, Travis E Walk, Linda L Ballard, Sheron A Simpson, Naveen Puppala, Brian E Scheffler, Francisco de Blas, Guillermo J Seijo
BACKGROUND: Aflatoxin contamination in peanut seeds is still a serious problem for the industry and human health. No stable aflatoxin resistant cultivars have yet been produced, and given the narrow genetic background of cultivated peanuts, wild species became an important source of genetic diversity. Wild peanut seeds, however, are not abundant, thus, an effective method of screening for aflatoxin accumulation using minimal seeds is highly desirable. In addition, keeping record of genetic fingerprinting of each accession would be very useful for breeding programs and for the identification of accessions within germplasm collections...
August 15, 2018: BMC Plant Biology
Esra Nurten Yer, Mehmet Cengiz Baloglu, Sezgin Ayan
Heat shock proteins (Hsps) play a key role for regulation of the changes during different stress conditions including salinity, drought, heavy metal and extreme temperature. Molecular based studies on the response mechanisms of forest trees to abiotic stresses started in 2006 when Populus trichocarpa genome sequence was completed as a model tree species. In recent years, bioinformatic analyzes have been carried out to determine functional gene regions of tree species. In this study, sHsp, Hsp40, Hsp60, Hsp90 and Hsp100 gene family members were identified in poplar genome...
August 12, 2018: Gene
Andreas Hofmann, Dieter W Heermann
In order to interpret data from Hi-C studies genome-wide contact probability maps need to be translated into models of functional 3D genome organization. Here, we first present an overview of computational methods to analyze contact probability maps in terms of features such as the level and shape of compartmentalization. Next, we describe approaches to modeling 3D genome organization based on Hi-C data.
2018: Methods in Molecular Biology
Frédéric G Crémazy, Fatema-Zahra M Rashid, James R Haycocks, Lisa E Lamberte, David C Grainger, Remus T Dame
The spatial organization of genomes is based on their hierarchical compartmentalization in topological domains. There is growing evidence that bacterial genomes are organized into insulated domains similar to the Topologically Associating Domains (TADs) detected in eukaryotic cells. Chromosome conformation capture (3C) technologies are used to analyze in vivo DNA proximity based on ligation of distal DNA segments crossed-linked by bridging proteins. By combining 3C and high-throughput sequencing, the Hi-C method reveals genome-wide interactions within topological domains and global genome structure as a whole...
2018: Methods in Molecular Biology
Bingzheng Shen, Jinchun Song, Yonghui Zhao, Yaoyun Zhang, Gaomin Liu, Xueke Li, Xingchen Guo, Wenxin Li, Zhijian Cao, Yingliang Wu
Since there is a symbiotic and competitive relationship between microorganisms in the same ecological niche, fungal defensins have been found to be important resources for antimicrobial peptides. Here, a fungal defensin, triintsin, was characterized in a clinical isolate of Trichophytoninterdigitale from a patient with onychomycosis. The comparison of its genomic and mRNA sequences showed the gene organization and structure of three coding exons separated by two introns. The precursor peptide of triintsin contained 85 amino acid residues, which were composed of three parts including an N-terminal signal domain of 21 residues, a pro-peptide of 47 residues that ended at lysine-arginine and a mature peptide of 38 residues at the C-terminus...
August 10, 2018: Peptides
Jinghong Zuo, Jindong Liu, Fengmei Gao, Guihong Yin, Zhi Wang, Fengying Chen, Xiaoying Li, Jimei Xu, Tiantian Chen, Lei Li, Yu Li, Xianchun Xia, Hong Cao, Yongxiu Liu
Long-term storage of seeds leads to lose seed vigor with slow and non-uniform germination. Time, rate, homogeneity, and synchrony are important aspects during the dynamic germination process to assess seed viability after storage. The aim of this study is to identify quantitative trait loci (QTLs) using a high-density genetic linkage map of common wheat ( Triticum aestivum ) for seed vigor-related traits under artificial aging. Two hundred and forty-six recombinant inbred lines derived from the cross between Zhou 8425B and Chinese Spring were evaluated for seed storability...
2018: Frontiers in Plant Science
Danyan Gao, Bijun Zhu, Xin Cao, Miaomiao Zhang, Xiangdong Wang
A cohesin-loading factor (NIPBL) is one of important regulatory factors in the maintenance of 3D genome organization and function, by interacting with a large number of factors, e.g. cohesion, CCCTC-binding factor (CTCF) or cohesin complex component. The present article overviews the critical and regulatory roles of NIBPL in cohesion loading on chromotin and in gene expression and transcriptional signaling. We explore molecular mechanisms by which NIPBL recruits endogenous histone deacetylase (HDAC) to induce histone deacetylation and influence multi-dimensions of genome, through which NIPBL "hop" movement in chromatin regulates gene expression and alters genome folding...
August 7, 2018: Seminars in Cell & Developmental Biology
Camille Clément, Guillermo A Orsi, Alberto Gatto, Ekaterina Boyarchuk, Audrey Forest, Bassam Hajj, Judith Miné-Hattab, Mickaël Garnier, Zachary A Gurard-Levin, Jean-Pierre Quivy, Geneviève Almouzni
DNA replication is a challenge for the faithful transmission of parental information to daughter cells, as both DNA and chromatin organization must be duplicated. Replication stress further complicates the safeguard of epigenome integrity. Here, we investigate the transmission of the histone variants H3.3 and H3.1 during replication. We follow their distribution relative to replication timing, first in the genome and, second, in 3D using super-resolution microscopy. We find that H3.3 and H3.1 mark early- and late-replicating chromatin, respectively...
August 9, 2018: Nature Communications
Michael T Zimmermann, Raul Urrutia, Margot A Cousin, Gavin R Oliver, Eric W Klee
Purpose: Demand is increasing for clinical genomic sequencing to provide diagnoses for patients presenting phenotypes indicative of genetic diseases, but for whom routine genetic testing failed to yield a diagnosis. DNA-based testing using high-throughput technologies often identifies variants with insufficient evidence to determine whether they are disease-causal or benign, leading to categorization as variants of uncertain significance (VUS). Methods: We used molecular modeling and simulation to generate specific hypotheses for the molecular effects of variants in the human glucose transporter, GLUT10 ( SLC2A10 )...
2018: Frontiers in Genetics
Sarah J Aitken, Ximena Ibarra-Soria, Elissavet Kentepozidou, Paul Flicek, Christine Feig, John C Marioni, Duncan T Odom
BACKGROUND: CTCF binding to DNA helps partition the mammalian genome into discrete structural and regulatory domains. Complete removal of CTCF from mammalian cells causes catastrophic genome dysregulation, likely due to widespread collapse of 3D chromatin looping and alterations to inter- and intra-TAD interactions within the nucleus. In contrast, Ctcf hemizygous mice with lifelong reduction of CTCF expression are viable, albeit with increased cancer incidence. Here, we exploit chronic Ctcf hemizygosity to reveal its homeostatic roles in maintaining genome function and integrity...
August 7, 2018: Genome Biology
Abhishek Shrivastava, Visha K Patel, Yisha Tang, Susan Connolly Yost, Floyd E Dewhirst, Howard C Berg
The human microbiome is an assemblage of diverse bacteria that interact with one another to form communities. Bacteria in a given community are arranged in a 3D matrix with many degrees of freedom. Snapshots of the community display well-defined structures, but the steps required for their assembly are not understood. Here, we show that this construction is carried out with the help of gliding bacteria. Gliding is defined as the motion of cells over a solid or semisolid surface without the necessity of growth or the aid of pili or flagella...
August 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
Benjamin D Landry, Thomas Leete, Ryan Richards, Peter Cruz-Gordillo, Hannah R Schwartz, Megan E Honeywell, Gary Ren, Alyssa D Schwartz, Shelly R Peyton, Michael J Lee
Due to tumor heterogeneity, most believe that effective treatments should be tailored to the features of an individual tumor or tumor subclass. It is still unclear, however, what information should be considered for optimal disease stratification, and most prior work focuses on tumor genomics. Here, we focus on the tumor microenvironment. Using a large-scale coculture assay optimized to measure drug-induced cell death, we identify tumor-stroma interactions that modulate drug sensitivity. Our data show that the chemo-insensitivity typically associated with aggressive subtypes of breast cancer is not observed if these cells are grown in 2D or 3D monoculture, but is manifested when these cells are cocultured with stromal cells, such as fibroblasts...
August 6, 2018: Molecular Systems Biology
Haishuang Lin, Qian Du, Qiang Li, Ou Wang, Zhanqi Wang, Neety Sahu, Christian Elowsky, Kan Liu, Chi Zhang, Soonkyu Chung, Bin Duan, Yuguo Lei
Endothelial cells (ECs) are of great value for cell therapy, tissue engineering, and drug discovery. Obtaining high-quantity and -quality ECs remains very challenging. Here, we report a method for the scalable manufacturing of ECs from human pluripotent stem cells (hPSCs). hPSCs are expanded and differentiated into ECs in a 3D thermoreversible PNIPAAm-PEG hydrogel. The hydrogel protects cells from hydrodynamic stresses in the culture vessel and prevents cells from excessive agglomeration, leading to high-culture efficiency including high-viability (>90%), high-purity (>80%), and high-volumetric yield (2...
July 27, 2018: Stem Cell Reports
Nicole Rusk
No abstract text is available yet for this article.
August 2018: Nature Methods
Ezgi Süheyla Doğan, Chang Liu
Information and function of a genome are not only decorated with epigenetic marks in the linear DNA sequence but also in their non-random spatial organization in the nucleus. Recent research has revealed that three-dimensional (3D) chromatin organization is highly correlated with the functionality of the genome, contributing to many cellular processes. Driven by the improvements in chromatin conformation capture methods and visualization techniques, the past decade has been an exciting period for the study of plants' 3D genome structures, and our knowledge in this area has been substantially advanced...
August 2018: Nature Plants
Sen Liang, Rongguo Zhang, Dayang Liang, Tianci Song, Tao Ai, Chen Xia, Liming Xia, Yan Wang
Non-invasive prediction of isocitrate dehydrogenase ( IDH ) genotype plays an important role in tumor glioma diagnosis and prognosis. Recently, research has shown that radiology images can be a potential tool for genotype prediction, and fusion of multi-modality data by deep learning methods can further provide complementary information to enhance prediction accuracy. However, it still does not have an effective deep learning architecture to predict IDH genotype with three-dimensional (3D) multimodal medical images...
July 30, 2018: Genes
Suolan Fu, Linlin Zhang, Jiapei Lv, Bijun Zhu, Wei Wang, Xiangdong Wang
Multi-dimensions dynamics of the genome play important roles in the maintenance of cell function, regulation of transcriptional signals and occurrence of diseases. With rapid development of methodologies, the genome organization and structure are found as three-dimensional (3D) or with dynamic changes (4D), and regulated by a large number of factors. The present article aims to overview the 3C derivation method Hi-C and ChIA-PET assay technologies coupled with new data analysis methods, capture the spatial interactions between different loci across the entire genome, reveal the regularity of the genome spatial structure...
July 27, 2018: Seminars in Cell & Developmental Biology
Xiangdong Wang
The present issue with enthusiasm overviews technologies to detect 3D genome structures, relationship of 3D genome and diseases, and potential mechanism of regulatory elements to maintain 3D genome stability. Rapid development of biotechnology provides more powerful approach to monitor dynamic changes of genome dimensions and organization as well as function. Disorganization and dysfunction of 3D genome, compartments, TADs, chromosomal loops, and intranuclear microenvironments play central roles in initiation and pathogenesis of diseases and cell sensitivity to therapy...
July 27, 2018: Seminars in Cell & Developmental Biology
Olutobi Oyinlade, Shuang Wei, Kai Kammers, Sheng Liu, Shuyan Wang, Ding Ma, Zhi-Yong Huang, Jiang Qian, Heng Zhu, Jun Wan, Shuli Xia
Recent studies have revealed an unexpected role of DNA methylation at promoter regions in transcription activation. However, whether DNA methylation at enhancer regions activates gene expression and influences cellular functions remains to be determined. In this study, by employing the transcription factor krÜppel-like factor 4 (KLF4) that binds to methylated CpGs (mCpGs), we investigated the molecular outcomes of the recruitment of KLF4 to mCpGs at enhancer regions in human glioblastoma cells. First, by integrating KLF4 ChIP-seq, whole-genome bisulfite sequence, and H3K27ac ChIP-seq datasets, we found 1,299 highly methylated (β >0...
July 30, 2018: Epigenetics: Official Journal of the DNA Methylation Society
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