scholarly journals A Multigraph model of the 3D genome

2021 ◽  
Author(s):  
Diana Makai ◽  
Andras Cseh ◽  
Adel Sepsi ◽  
Szabolcs Makai
Keyword(s):  
Information Needs ◽  
Dimensional Space ◽  
Decisive Role ◽  
Regulatory Elements ◽  
Sequence Information ◽  
Genomic Context ◽  
3D Genome ◽  
Flexible Polymer ◽  
Novel Approach ◽  
Contact Data

Spatial organisation of the genome has a fundamental effect on its biological functions. Chromatin-chromatin interactions and 3D spatial structures are involved in transcriptional regulation and have a decisive role in DNA replication and repair. To understand how individual genes and their regulatory elements function within the larger genomic context, and how the genome reacts as a whole to environmental stimuli, the linear sequence information needs to be interpreted in 3-dimensional space. While recent advances in chromatin conformation capture technologies including Hi-C, considerably advanced our understanding of the genomes, defining the DNA, as it is organized in the cell nucleus is still a challenging task. 3D genome modelling needs to reflect the DNA as a flexible polymer, which can wind up to the fraction of its total length and greatly unwind and stretch to implement a multitude of functions. Here we propose a novel approach to model genomes as a multigraph based on Hi-C contact data. Multigraph-based 3D genome modelling of barley and rice revealed the well-known Rabl and Rosetta chromatin organizations, respectively, as well as other higher order structures. Our results shows that the well-established toolset of Graph theory is highly valuable in modelling large genomes in 3D.

scholarly journals EPCO-31. EPIGENOMIC INTRATUMORAL HETEROGENEITY OF GLIOBLASTOMA IN THREE-DIMENSIONAL SPACE

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii76-ii76
Author(s):  
Radhika Mathur ◽  
Sriranga Iyyanki ◽  
Stephanie Hilz ◽  
Chibo Hong ◽  
Joanna Phillips ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Dimensional Space ◽  
Three Dimensional ◽  
Spatial Location ◽  
Therapy Resistance ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Intratumoral Heterogeneity ◽  
Tumor Evolution ◽  
Open Chromatin

Abstract Treatment failure in glioblastoma is often attributed to intratumoral heterogeneity (ITH), which fosters tumor evolution and generation of therapy-resistant clones. While ITH in glioblastoma has been well-characterized at the genomic and transcriptomic levels, the extent of ITH at the epigenomic level and its biological and clinical significance are not well understood. In collaboration with neurosurgeons, neuropathologists, and biomedical imaging experts, we have established a novel topographical approach towards characterizing epigenomic ITH in three-dimensional (3-D) space. We utilize pre-operative MRI scans to define tumor volume and then utilize 3-D surgical neuro-navigation to intra-operatively acquire 10+ samples representing maximal anatomical diversity. The precise spatial location of each sample is mapped by 3-D coordinates, enabling tumors to be visualized in 360-degrees and providing unprecedented insight into their spatial organization and patterning. For each sample, we conduct assay for transposase-accessible chromatin using sequencing (ATAC-Seq), which provides information on the genomic locations of open chromatin, DNA-binding proteins, and individual nucleosomes at nucleotide resolution. We additionally conduct whole-exome sequencing and RNA sequencing for each spatially mapped sample. Integrative analysis of these datasets reveals distinct patterns of chromatin accessibility within glioblastoma tumors, as well as their associations with genetically defined clonal expansions. Our analysis further reveals how differences in chromatin accessibility within tumors reflect underlying transcription factor activity at gene regulatory elements, including both promoters and enhancers, and drive expression of particular gene expression sets, including neuronal and immune programs. Collectively, this work provides the most comprehensive characterization of epigenomic ITH to date, establishing its importance for driving tumor evolution and therapy resistance in glioblastoma. As a resource for further investigation, we have provided our datasets on an interactive data sharing platform – The 3D Glioma Atlas – that enables 360-degree visualization of both genomic and epigenomic ITH.

scholarly journals Spatial organization of transcript elongation and splicing kinetics

2021 ◽  
Author(s):  
Alyssa D. Casill ◽  
Adam J. Haimowitz ◽  
Brian Kosmyna ◽  
Charles C. Query ◽  
Kenny Ye ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Spatial Organization ◽  
Dimensional Space ◽  
Three Dimensional ◽  
Regulatory Elements ◽  
Multiple Control ◽  
Pol Ii ◽  
Topologically Associated Domains ◽  
Transcript Elongation ◽  
Kinetics Of

SummaryThe organization of the genome in three-dimensional space has been shown to play an important role in gene expression. Specifically, facets of genomic interaction such as topologically associated domains (TADs) have been shown to regulate transcription by bringing regulatory elements into close proximity1. mRNA production is an intricate process with multiple control points including regulation of Pol II elongation and the removal of non-coding sequences via pre-mRNA splicing2. The connection between genomic compartments and the kinetics of RNA biogenesis and processing has been largely unexplored. Here, we measure Pol II elongation and splicing kinetics genome-wide using a novel technique that couples nascent RNA-seq with a mathematical model of transcription and co-transcriptional RNA processing. We uncovered multiple layers of spatial organization of these rates: the rate of splicing is coordinated across introns within individual genes, and both elongation and splicing rates are coordinated within TADs, as are alternative splicing outcomes. Overall, our work establishes that the kinetics of transcription and splicing are coordinated by the spatial organization of the genome and suggests that TADs are a major platform for coordination of alternative splicing.

scholarly journals Antioptimization of earthquake exitation and response

1998 ◽  
Vol 4 (1) ◽  
pp. 1-19 ◽  
Author(s):  
G. Zuccaro ◽  
I. Elishakoff ◽  
A. Baratta
Keyword(s):  
Historical Data ◽  
Dimensional Space ◽  
Stochastic Approach ◽  
Viable Alternative ◽  
Maximum Response ◽  
Minimum Volume ◽  
Earthquake Excitation ◽  
Novel Approach ◽  
Space Modeling ◽  
Minimum Volume Ellipsoid

The paper presents a novel approach to predict the response of earthquake-excited structures. The earthquake excitation is expanded in terms of series of deterministic functions. The coefficients of the series are represented as a point inN-dimensional space. Each available ccelerogram at a certain site is then represented as a point in the above space, modeling the available fragmentary historical data. The minimum volume ellipsoid, containing all points, is constructed. The ellipsoidal models of uncertainty, pertinent to earthquake excitation, are developed. The maximum response of a structure, subjected to the earthquake excitation, within ellipsoidal modeling of the latter, is determined. This procedure of determining least favorable response was termed in the literature (Elishakoff, 1991) as an antioptimization. It appears that under inherent uncertainty of earthquake excitation, antioptimization analysis is a viable alternative to stochastic approach.

scholarly journals Studying 3D genome evolution using genomic sequence

2019 ◽  
Author(s):  
Raphaël Mourad
Keyword(s):  
Genome Evolution ◽  
Genomic Sequence ◽  
Regulation Of Gene Expression ◽  
Replication Timing ◽  
Evolutionary Constraints ◽  
3D Genome ◽  
Chromatin Looping ◽  
Novel Approach ◽  
Evolutionary Studies ◽  
Ancestral Character Reconstruction

AbstractThe 3D genome is essential to numerous key processes such as the regulation of gene expression and the replication-timing program. In vertebrates, chromatin looping is often mediated by CTCF, and marked by CTCF motif pairs in convergent orientation. Comparative Hi-C recently revealed that chromatin looping evolves across species. However, Hi-C experiments are complex and costly, which currently limits their use for evolutionary studies over a large number of species. Here, we propose a novel approach to study the 3D genome evolution in vertebrates using the genomic sequence only, e.g. without the need for Hi-C data. The approach is simple and relies on comparing the distances between convergent and divergent CTCF motifs (ratio R). We show that R is a powerful statistic to detect CTCF looping encoded in the human genome sequence, thus reflecting strong evolutionary constraints encoded in DNA and associated with the 3D genome. When comparing vertebrate genomes, our results reveal that R which underlies CTCF looping and TAD organization evolves over time and suggest that ancestral character reconstruction can be used to infer R in ancestral genomes.

A NOVEL APPROACH FOR SEMANTIC WEB APPLICATION IN ONLINE EDUCATION BASED ON STEGANOGRAPHY

2022 ◽  
Vol 17 (4) ◽  
pp. 0-0
Keyword(s):  
Online Education ◽  
Semantic Web ◽  
Web 2.0 ◽  
Language Processing ◽  
Web Application ◽  
Information Needs ◽  
Extensive Literature ◽  
Web 3.0 ◽  
Novel Approach ◽  
Current Concerns

Semantic Web technology is not new as most of us contemplate; it has evolved over the years. Linked Data web terminology is the name set recently to the Semantic Web. Semantic Web is a continuation of Web 2.0 and it is to replace existing technologies. It is built on Natural Language processing and provides solutions to most of the prevailing issues. Web 3.0 is the version of Semantic Web caters to the information needs of half of the population on earth. This paper links two important current concerns, the security of information and enforced online education due to COVID-19 with Semantic Web. The Steganography requirement for the Semantic web is discussed elaborately, even though encryption is applied which is inadequate in providing protection. Web 2.0 issues concerning online education and semantic Web solutions have been discussed. An extensive literature survey has been conducted related to the architecture of Web 3.0, detailed history of online education, and Security architecture. Finally, Semantic Web is here to stay and data hiding along with encryption makes it robust.

scholarly journals Studying 3D genome evolution using genomic sequence

2019 ◽  
Author(s):  
Raphaël Mourad
Keyword(s):  
Genome Evolution ◽  
High Throughput Sequencing ◽  
Genomic Sequence ◽  
Regulation Of Gene Expression ◽  
Replication Timing ◽  
Three Dimensions ◽  
Supplementary Information ◽  
3D Genome ◽  
Chromatin Looping ◽  
Novel Approach

Abstract Motivation The three dimensions (3D) genome is essential to numerous key processes such as the regulation of gene expression and the replication-timing program. In vertebrates, chromatin looping is often mediated by CTCF, and marked by CTCF motif pairs in convergent orientation. Comparative high-throughput sequencing technique (Hi-C) recently revealed that chromatin looping evolves across species. However, Hi-C experiments are complex and costly, which currently limits their use for evolutionary studies over a large number of species. Results Here, we propose a novel approach to study the 3D genome evolution in vertebrates using the genomic sequence only, e.g. without the need for Hi-C data. The approach is simple and relies on comparing the distances between convergent and divergent CTCF motifs by computing a ratio we named the 3D ratio or ‘3DR’. We show that 3DR is a powerful statistic to detect CTCF looping encoded in the human genome sequence, thus reflecting strong evolutionary constraints encoded in DNA and associated with the 3D genome. When comparing vertebrate genomes, our results reveal that 3DR which underlies CTCF looping and topologically associating domain organization evolves over time and suggest that ancestral character reconstruction can be used to infer 3DR in ancestral genomes. Availability and implementation The R code is available at https://github.com/morphos30/PhyloCTCFLooping. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals The DLO Hi-C Tool for Digestion-Ligation-Only Hi-C Chromosome Conformation Capture Data Analysis

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 289 ◽  
Author(s):  
Ping Hong ◽  
Hao Jiang ◽  
Weize Xu ◽  
Da Lin ◽  
Qian Xu ◽  
...  
Keyword(s):  
Target Genes ◽  
High Efficiency ◽  
New Technology ◽  
Three Dimensional ◽  
Large Data ◽  
Regulatory Elements ◽  
Chromosome Conformation Capture ◽  
Genome Chromosome ◽  
Chromosome Conformation ◽  
3D Genome

It is becoming increasingly important to understand the mechanism of regulatory elements on target genes in long-range genomic distance. 3C (chromosome conformation capture) and its derived methods are now widely applied to investigate three-dimensional (3D) genome organizations and gene regulation. Digestion-ligation-only Hi-C (DLO Hi-C) is a new technology with high efficiency and cost-effectiveness for whole-genome chromosome conformation capture. Here, we introduce the DLO Hi-C tool, a flexible and versatile pipeline for processing DLO Hi-C data from raw sequencing reads to normalized contact maps and for providing quality controls for different steps. It includes more efficient iterative mapping and linker filtering. We applied the DLO Hi-C tool to different DLO Hi-C datasets and demonstrated its ability in processing large data with multithreading. The DLO Hi-C tool is suitable for processing DLO Hi-C and in situ DLO Hi-C datasets. It is convenient and efficient for DLO Hi-C data processing.

scholarly journals A map of cis-regulatory elements and 3D genome structures in zebrafish

Nature ◽  
2020 ◽  
Vol 588 (7837) ◽  
pp. 337-343
Author(s):  
Hongbo Yang ◽  
Yu Luan ◽  
Tingting Liu ◽  
Hyung Joo Lee ◽  
Li Fang ◽  
...  
Keyword(s):  
Regulatory Elements ◽  
3D Genome

scholarly journals Ad5/35E1aPSESE4: A novel approach to marking circulating prostate tumor cells with a replication competent adenovirus controlled by PSA/PSMA transcription regulatory elements

2016 ◽  
Vol 372 (1) ◽  
pp. 57-64 ◽  
Author(s):  
Ji-Eun Hwang ◽  
Jae Young Joung ◽  
Seung-Phil Shin ◽  
Moon-Kyung Choi ◽  
Jeong Eun Kim ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Regulatory Elements ◽  
Prostate Tumor ◽  
Novel Approach ◽  
Prostate Tumor Cells

scholarly journals Novel Insights into the Classification of Staphylococcal β-Lactamases in Relation to the Cefazolin Inoculum Effect

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Lina P. Carvajal ◽  
Sandra Rincon ◽  
Aura M. Echeverri ◽  
Jessica Porras ◽  
Rafael Rios ◽  
...  
Keyword(s):  
Phylogenetic Analyses ◽  
Sequence Information ◽  
Content Type ◽  
Novel Approach ◽  
Important Concern ◽  
High Prevalence ◽  
Type C ◽  
Inoculum Effect ◽  
Limited Sequence

ABSTRACT Cefazolin has become a prominent therapy for methicillin-susceptible Staphylococcus aureus (MSSA) infections. However, an important concern is the cefazolin inoculum effect (CzIE), a phenomenon mediated by staphylococcal β-lactamases. Four variants of staphylococcal β-lactamases have been described based on serological methodologies and limited sequence information. Here, we sought to reassess the classification of staphylococcal β-lactamases and their correlation with the CzIE. We included a large collection of 690 contemporary bloodstream MSSA isolates recovered from Latin America, a region with a high prevalence of the CzIE. We determined cefazolin MICs at standard and high inoculums by broth microdilution. Whole-genome sequencing was performed to classify the β-lactamase in each isolate based on the predicted full sequence of BlaZ. We used the classical schemes for β-lactamase classification and compared it to BlaZ allotypes found in unique sequences using the genomic information. Phylogenetic analyses were performed based on the BlaZ and core-genome sequences. The overall prevalence of the CzIE was 40%. Among 641 genomes, type C was the most predominant β-lactamase (37%), followed by type A (33%). We found 29 allotypes and 43 different substitutions in BlaZ. A single allotype, designated BlaZ-2, showed a robust and statistically significant association with the CzIE. Two other allotypes (BlaZ-3 and BlaZ-5) were associated with a lack of the CzIE. Three amino acid substitutions (A9V, E112A, and G145E) showed statistically significant association with the CzIE (P = <0.01). CC30 was the predominant clone among isolates displaying the CzIE. Thus, we provide a novel approach to the classification of the staphylococcal β-lactamases with the potential to more accurately identify MSSA strains exhibiting the CzIE.

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