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3D genomics

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https://read.qxmd.com/read/30767777/biovr-a-platform-for-virtual-reality-assisted-biological-data-integration-and-visualization
#1
Jimmy F Zhang, Alex R Paciorkowski, Paul A Craig, Feng Cui
BACKGROUND: Functional characterization of single nucleotide variants (SNVs) involves two steps, the first step is to convert DNA to protein and the second step is to visualize protein sequences with their structures. As massively parallel sequencing has emerged as a leading technology in genomics, resulting in a significant increase in data volume, direct visualization of SNVs together with associated protein sequences/structures in a new user interface (UI) would be a more effective way to assess their potential effects on protein function...
February 15, 2019: BMC Bioinformatics
https://read.qxmd.com/read/30767736/3d-printing-in-personalized-drug-delivery
#2
Afsana, Vineet Jain, Nafis Haider, Keerti Jain
BACKGROUND: Personalized medicines are becoming more popular as they enables the use of patient's genomics and hence help in better drug design with fewer side effects. In fact several doses can be combined into one dosage form which suits the patient's demography. 3 Dimensional (3D) printing technology for personalized medicine is a modern day treatment method based on genomics of patient. METHODS: 3D printing technology uses digitally controlled devices for formulating API and excipients in a layer by layer pattern for developing a suitable personalized drug delivery system as per the need of patient...
February 15, 2019: Current Pharmaceutical Design
https://read.qxmd.com/read/30759402/pyminer-finds-gene-and-autocrine-paracrine-networks-from-human-islet-scrna-seq
#3
Scott R Tyler, Pavana G Rotti, Xingshen Sun, Yaling Yi, Weiliang Xie, Michael C Winter, Miles J Flamme-Wiese, Budd A Tucker, Robert F Mullins, Andrew W Norris, John F Engelhardt
Toolsets available for in-depth analysis of scRNA-seq datasets by biologists with little informatics experience is limited. Here, we describe an informatics tool (PyMINEr) that fully automates cell type identification, cell type-specific pathway analyses, graph theory-based analysis of gene regulation, and detection of autocrine-paracrine signaling networks in silico. We applied PyMINEr to interrogate human pancreatic islet scRNA-seq datasets and discovered several features of co-expression graphs, including concordance of scRNA-seq-graph structure with both protein-protein interactions and 3D genomic architecture, association of high-connectivity and low-expression genes with cell type enrichment, and potential for the graph structure to clarify potential etiologies of enigmatic disease-associated variants...
February 12, 2019: Cell Reports
https://read.qxmd.com/read/30755082/role-of-lamins-in-3d-genome-organization-and-global-gene-expression
#4
Youngjo Kim, Xiaobin Zheng, Yixian Zheng
Genome-wide mapping of lamin-B1-genome interactions has shown that gene-poor and transcriptionally inactive genomic regions are associated with the nuclear lamina. Numerous studies have suggested that lamins, the major structural components of the nuclear lamina, play a role in global chromatin organization and gene expression. How lamins could influence the 3D genome organization and transcription from the nuclear periphery has, however, remained unclear. Our recent studies showed that lamins differentially regulate distinct lamina-associated chromatin domains (LADs) at the nuclear periphery, which can in turn influence global 3D genome organization and gene expression...
December 2019: Nucleus
https://read.qxmd.com/read/30746589/production-of-functional-recombinant-cyclic-citrullinated-peptide-monoclonal-antibody-in-transgenic-rice-cell-suspension-culture
#5
Do Van Giap, Jae-Wan Jung, Nan-Sun Kim
Cyclic citrullinated peptide (CCP) antibody has been shown recently to be a promising marker for early detection and diagnosis of rheumatoid arthritis (RA). In order to exploit newly developed therapies for RA, early intervention is crucial in preventing irreversible joint damage. Here, we describe use of a plant expression system to produce a CCP antibody that could be used in the early diagnosis of RA. Heavy and light chain gene sequences of a CCP monoclonal antibody (CCP mAb) were cloned from the hybridoma cell (12G1) and introduced into two separate plant expression vectors under the control of the rice α-amylase 3D (RAmy3D) promoter system...
February 11, 2019: Transgenic Research
https://read.qxmd.com/read/30745086/oncogenic-notch-promotes-long-range-regulatory-interactions-within-hyperconnected-3d-cliques
#6
Jelena Petrovic, Yeqiao Zhou, Maria Fasolino, Naomi Goldman, Gregory W Schwartz, Maxwell R Mumbach, Son C Nguyen, Kelly S Rome, Yogev Sela, Zachary Zapataro, Stephen C Blacklow, Michael J Kruhlak, Junwei Shi, Jon C Aster, Eric F Joyce, Shawn C Little, Golnaz Vahedi, Warren S Pear, Robert B Faryabi
Chromatin loops enable transcription-factor-bound distal enhancers to interact with their target promoters to regulate transcriptional programs. Although developmental transcription factors such as active forms of Notch can directly stimulate transcription by activating enhancers, the effect of their oncogenic subversion on the 3D organization of cancer genomes is largely undetermined. By mapping chromatin looping genome-wide in Notch-dependent triple-negative breast cancer and B cell lymphoma, we show that beyond the well-characterized role of Notch as an activator of distal enhancers, Notch regulates its direct target genes by instructing enhancer repositioning...
February 5, 2019: Molecular Cell
https://read.qxmd.com/read/30737956/developing-scalable-cultivation-systems-of-hepatic-spheroids-for-drug-metabolism-via-genomic-and-functional-analyses
#7
Jiwon Ahn, Ho-Joon Lee, Soo Jin Oh, Wantae Kim, Seon Ju Mun, Jae-Hye Lee, Cho-Rock Jung, Hyun-Soo Cho, Dae-Soo Kim, Myung Jin Son, Kyung-Sook Chung
Spheroids, a widely used three-dimensional (3D) culture model, are standard in hepatocyte culture as they preserve long-term hepatocyte functionality and enhance survivability. In this study, we investigated the effects of three operation modes in 3D culture - static, orbital shaking, and under vertical bidirectional flow using spheroid forming units (SFUs) - on hepatic differentiation and drug metabolism to propose the best for mass production of functionally enhanced spheroids. Spheroids in SFUs exhibited increased hepatic gene expression, albumin secretion, and cytochrome P450 3A4 (CYP3A4) activity during the differentiation period (12 days)...
February 9, 2019: Biotechnology and Bioengineering
https://read.qxmd.com/read/30735630/replication-timing-becomes-intertwined-with-3d-genome-organization
#8
Jian Ma, Zhijun Duan
Through dissecting the link between spatial genome organization and DNA replication timing, Sima et al. (2018) discover early replicating control elements (ERCEs), a new type of cis-acting elements that regulate replication timing, transcription, and multiple layers of three-dimensional features of genome organization. The study has important implications for unraveling control elements of high-order genome structure and function.
February 7, 2019: Cell
https://read.qxmd.com/read/30735225/an-ultrasensitive-test-for-profiling-circulating-tumor-dna-using-integrated-comprehensive-droplet-digital-detection
#9
Chen-Yin Ou, Tam Vu, Jonathan T Grunwald, Michael Toledano, Jan Zimak, Melody Toosky, Byron Shen, Jason A Zell, Enrico Gratton, Timothy J Abram, Weian Zhao
Current cancer detection systems lack the required sensitivity to reliably detect minimal residual disease (MRD) and recurrence at the earliest stages when treatment would be most effective. To address this issue, we present a novel liquid biopsy approach that utilizes an integrated comprehensive droplet digital detection (IC3D) digital PCR system which combines microfluidic droplet partitioning, fluorescent multiplex PCR chemistry, and our rapid 3D, large-volume droplet counting technology. The IC3D ddPCR assay can detect cancer-specific, ultra-rare genomic targets due to large sample input and high degree of partitioning...
February 8, 2019: Lab on a Chip
https://read.qxmd.com/read/30723152/comparative-3d-genome-organization-in-apicomplexan-parasites
#10
Evelien M Bunnik, Aarthi Venkat, Jianlin Shao, Kathryn E McGovern, Gayani Batugedara, Danielle Worth, Jacques Prudhomme, Stacey A Lapp, Chiara Andolina, Leila S Ross, Lauren Lawres, Declan Brady, Photini Sinnis, Francois Nosten, David A Fidock, Emma H Wilson, Rita Tewari, Mary R Galinski, Choukri Ben Mamoun, Ferhat Ay, Karine G Le Roch
The positioning of chromosomes in the nucleus of a eukaryotic cell is highly organized and has a complex and dynamic relationship with gene expression. In the human malaria parasite Plasmodium falciparum , the clustering of a family of virulence genes correlates with their coordinated silencing and has a strong influence on the overall organization of the genome. To identify conserved and species-specific principles of genome organization, we performed Hi-C experiments and generated 3D genome models for five Plasmodium species and two related apicomplexan parasites...
February 5, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/30723106/lineage-specific-reorganization-of-nuclear-peripheral-heterochromatin-and-h3k9me2-domains
#11
Kelvin See, Yemin Lan, Joshua Rhoades, Rajan Jain, Cheryl L Smith, Jonathan A Epstein
Dynamic organization of chromatin within the three-dimensional nuclear space has been postulated to regulate gene expression and cell fate. Here, we define the genome-wide distribution of nuclear peripheral heterochromatin as a multipotent P19 cell adopts either a neural or a cardiac fate. We demonstrate that H3K9me2-marked nuclear peripheral heterochromatin undergoes lineage-specific reorganization during cell-fate determination. This is associated with spatial repositioning of genomic loci away from the nuclear periphery as shown by 3D immuno-FISH...
February 5, 2019: Development
https://read.qxmd.com/read/30717603/a-robust-ctcf-based-chromatin-architecture-underpins-epigenetic-changes-in-the-heart-failure-stress-gene-response
#12
Dominic Paul Lee, Wilson Lek Wen Tan, Chukwuemeka George Anene-Nzelu, Chang Jie Mick Lee, Peter Yiqing Li, Tuan Danh Anh, Cheryl Xueli Chan, Zenia Tiang, Shi Ling Ng, Xingfan Huang, Motakis Efthymios, Matias I Autio, Jianming Jiang, Melissa Jane Fullwood, Shyam Prabhakar, Erez Lieberman Aiden, Roger Sik-Yin Foo
BACKGROUND: The human genome folds in 3D to form thousands of chromatin loops inside the nucleus, encasing genes and cis-regulatory elements for accurate gene expression control. Physical tethers of loops are anchored by the DNA-binding protein CTCF and the cohesin ring complex. Since heart failure is characterised by hallmark gene expression changes, it was recently reported that substantial CTCF-related chromatin re-organisation underpins the myocardial stress-gene response, paralleled by chromatin domain boundary changes observed in CTCF knockout...
February 5, 2019: Circulation
https://read.qxmd.com/read/30713525/structural-characterization-of-the-xi-class-glutathione-transferase-from-the-haloalkaliphilic-archaeon-natrialba-magadii
#13
Adele Di Matteo, Luca Federici, Michele Masulli, Erminia Carletti, Daniele Santorelli, Jennifer Cassidy, Francesca Paradisi, Carmine Di Ilio, Nerino Allocati
Xi class glutathione transferases (GSTs) are a recently identified group, within this large superfamily of enzymes, specifically endowed with glutathione-dependent reductase activity on glutathionyl-hydroquinone. Enzymes belonging to this group are widely distributed in bacteria, fungi, and plants but not in higher eukaryotes. Xi class GSTs are also frequently found in archaea and here we focus on the enzyme produced by the extreme haloalkaliphilic archaeon Natrialba magadii (NmGHR). We investigated its function and stability and determined its 3D structure in the apo form by X-ray crystallography...
2019: Frontiers in Microbiology
https://read.qxmd.com/read/30713041/reprogramming-captures-the-genetic-and-tumorigenic-properties-of-neurofibromatosis-type-1-plexiform-neurofibromas
#14
Meritxell Carrió, Helena Mazuelas, Yvonne Richaud-Patin, Bernat Gel, Ernest Terribas, Imma Rosas, Senda Jimenez-Delgado, Josep Biayna, Leen Vendredy, Ignacio Blanco, Elisabeth Castellanos, Conxi Lázaro, Ángel Raya, Eduard Serra
Neurofibromatosis type 1 (NF1) is a tumor predisposition genetic disease caused by mutations in the NF1 tumor suppressor gene. Plexiform neurofibromas (PNFs) are benign Schwann cell (SC) tumors of the peripheral nerve sheath that develop through NF1 inactivation and can progress toward a malignant soft tissue sarcoma. There is a lack of non-perishable model systems to investigate PNF development. We reprogrammed PNF-derived NF1(-/-) cells, descendants from the tumor originating cell. These NF1(-/-)-induced pluripotent stem cells (iPSCs) captured the genomic status of PNFs and were able to differentiate toward neural crest stem cells and further to SCs...
January 17, 2019: Stem Cell Reports
https://read.qxmd.com/read/30712512/the-international-conference-on-intelligent-biology-and-medicine-icibm-2018-genomics-with-bigger-data-and-wider-applications
#15
EDITORIAL
Zhijin Wu, Jingwen Yan, Kai Wang, Xiaoming Liu, Yan Guo, Degui Zhi, Jianhua Ruan, Zhongming Zhao
The sixth International Conference on Intelligent Biology and Medicine (ICIBM) took place in Los Angeles, California, USA on June 10-12, 2018. This conference featured eleven regular scientific sessions, four tutorials, one poster session, four keynote talks, and four eminent scholar talks. The scientific program covered a wide range of topics from bench to bedside, including 3D Genome Organization, reconstruction of large scale evolution of genomes and gene functions, artificial intelligence in biological and biomedical fields, and precision medicine...
February 4, 2019: BMC Genomics
https://read.qxmd.com/read/30704510/the-international-conference-on-intelligent-biology-and-medicine-icibm-2018-genomics-meets-medicine
#16
EDITORIAL
Degui Zhi, Zhongming Zhao, Fuhai Li, Zhijin Wu, Xiaoming Liu, Kai Wang
During June 10-12, 2018, the International Conference on Intelligent Biology and Medicine (ICIBM 2018) was held in Los Angeles, California, USA. The conference included 11 scientific sessions, four tutorials, one poster session, four keynote talks and four eminent scholar talks that covered a wide range of topics ranging from 3D genome structure analysis and visualization, next generation sequencing analysis, computational drug discovery, medical informatics, cancer genomics to systems biology. While medical genomics has always been a main theme in ICIBM, this year we for the first time organized the BMC Medical Genomics Supplement for ICIBM...
January 31, 2019: BMC Medical Genomics
https://read.qxmd.com/read/30704480/identification-of-exon-skipping-events-associated-with-alzheimer-s-disease-in-the-human-hippocampus
#17
Seonggyun Han, Jason E Miller, Seyoun Byun, Dokyoon Kim, Shannon L Risacher, Andrew J Saykin, Younghee Lee, Kwangsik Nho
BACKGROUND: At least 90% of human genes are alternatively spliced. Alternative splicing has an important function regulating gene expression and miss-splicing can contribute to risk for human diseases, including Alzheimer's disease (AD). METHODS: We developed a splicing decision model as a molecular mechanism to identify functional exon skipping events and genetic variation affecting alternative splicing on a genome-wide scale by integrating genomics, transcriptomics, and neuroimaging data in a systems biology approach...
January 31, 2019: BMC Medical Genomics
https://read.qxmd.com/read/30704346/crispr-cas9-edited-hipsc-based-vascular-tissues-to-model-aging-and-disease-dependent-impairment
#18
Aylin Acun, Pinar Zorlutuna
The discovery of induced pluripotent stem cells (iPSCs) and advancements in genome editing technology introduced a new perspective to disease modeling as genetic factors can now be incorporated to mimic the pathology of interest. Ischemia and age-driven impairment of endothelium is one of the very important factors in the prognosis of many diseases as it leads to decreased angiogenic response and is shown to be related to age-dependent decrease in HIF-1α expression levels in endothelial cells. However, there are no models that show the characteristic age and ischemia-driven deterioration of the endothelium with both the functional and genetic mimicry...
February 1, 2019: Tissue Engineering. Part A
https://read.qxmd.com/read/30692846/genome-wide-analysis-of-domain-swap-predicted-products-in-the-genome-of-anti-stress-medicinal-plant-ocimum-tenuiflorum
#19
Atul Kumar Upadhyay, Ramanathan Sowdhamini
Computational approaches to high-throughput data are gaining importance because of explosion of sequences in the post-genomic era. This explosion of sequence data creates a huge gap among the domains of sequence structure and function, since the experimental techniques to determine the structure and function are very expensive, time taking, and laborious in nature. Therefore, there is an urgent need to emphasize on the development of computational approaches in the field of biological systems. Engagement of proteins in quaternary arrangements, such as domain swapping, might be relevant for higher compatibility of such genes at stress conditions...
2019: Bioinformatics and Biology Insights
https://read.qxmd.com/read/30670607/-aegilops-tauschii-genome-sequence-a-framework-for-meta-analysis-of-wheat-qtls
#20
Jiale Xu, Xiongtao Dai, Ramesh K Ramasamy, Le Wang, Tingting Zhu, Patrick E McGuire, Chad M Jorgensen, Hamid Dehghani, Patrick J Gulick, Ming-Cheng Luo, Hans-Georg Müller, Jan Dvorak
Numerous quantitative trait loci (QTLs) have been mapped in tetraploid and hexaploid wheat and wheat relatives, mostly with simple sequence repeat (SSR) or single nucleotide polymorphism (SNP) markers. To conduct meta-analysis of QTLs requires projecting them onto a common genomic framework, either a consensus genetic map or genomic sequence. The latter strategy is pursued here. Of 774 QTLs mapped in wheat and wheat relatives found in the literature, 585 (75.6%) were successfully projected onto the Aegilops tauschii pseudomolecules...
January 22, 2019: G3: Genes—Genomes—Genetics
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