Thematische Bibliographien / 3D genome structure

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  2. Dissertationen
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  4. Buchteile
  5. Konferenzberichte
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Auswahl der wissenschaftlichen Literatur zum Thema „3D genome structure“

Autor: Grafiati
Veröffentlicht am 18. Mai 2024

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Zeitschriftenartikel zum Thema "3D genome structure"

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Zhou, Tianming, Ruochi Zhang, and Jian Ma. "The 3D Genome Structure of Single Cells." Annual Review of Biomedical Data Science 4, no. 1 (2021): 21–41. http://dx.doi.org/10.1146/annurev-biodatasci-020121-084709.

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The spatial organization of the genome in the cell nucleus is pivotal to cell function. However, how the 3D genome organization and its dynamics influence cellular phenotypes remains poorly understood. The very recent development of single-cell technologies for probing the 3D genome, especially single-cell Hi-C (scHi-C), has ushered in a new era of unveiling cell-to-cell variability of 3D genome features at an unprecedented resolution. Here, we review recent developments in computational approaches to the analysis of scHi-C, including data processing, dimensionality reduction, imputation for enhancing data quality, and the revealing of 3D genome features at single-cell resolution. While much progress has been made in computational method development to analyze single-cell 3D genomes, substantial future work is needed to improve data interpretation and multimodal data integration, which are critical to reveal fundamental connections between genome structure and function among heterogeneous cell populations in various biological contexts.
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Mohanta, Tapan Kumar, Awdhesh Kumar Mishra, and Ahmed Al-Harrasi. "The 3D Genome: From Structure to Function." International Journal of Molecular Sciences 22, no. 21 (2021): 11585. http://dx.doi.org/10.3390/ijms222111585.

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The genome is the most functional part of a cell, and genomic contents are organized in a compact three-dimensional (3D) structure. The genome contains millions of nucleotide bases organized in its proper frame. Rapid development in genome sequencing and advanced microscopy techniques have enabled us to understand the 3D spatial organization of the genome. Chromosome capture methods using a ligation approach and the visualization tool of a 3D genome browser have facilitated detailed exploration of the genome. Topologically associated domains (TADs), lamin-associated domains, CCCTC-binding factor domains, cohesin, and chromatin structures are the prominent identified components that encode the 3D structure of the genome. Although TADs are the major contributors to 3D genome organization, they are absent in Arabidopsis. However, a few research groups have reported the presence of TAD-like structures in the plant kingdom.
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Huang, Kai, Yue Li, Anne R. Shim, et al. "Physical and data structure of 3D genome." Science Advances 6, no. 2 (2020): eaay4055. http://dx.doi.org/10.1126/sciadv.aay4055.

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With the textbook view of chromatin folding based on the 30-nm fiber being challenged, it has been proposed that interphase DNA has an irregular 10-nm nucleosome polymer structure whose folding philosophy is unknown. Nevertheless, experimental advances suggest that this irregular packing is associated with many nontrivial physical properties that are puzzling from a polymer physics point of view. Here, we show that the reconciliation of these exotic properties necessitates modularizing three-dimensional genome into tree data structures on top of, and in striking contrast to, the linear topology of DNA double helix. These functional modules need to be connected and isolated by an open backbone that results in porous and heterogeneous packing in a quasi–self-similar manner, as revealed by our electron and optical imaging. Our multiscale theoretical and experimental results suggest the existence of higher-order universal folding principles for a disordered chromatin fiber to avoid entanglement and fulfill its biological functions.
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Heinz, Sven, Lorane Texari, Michael G. B. Hayes, et al. "Transcription Elongation Can Affect Genome 3D Structure." Cell 174, no. 6 (2018): 1522–36. http://dx.doi.org/10.1016/j.cell.2018.07.047.

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Wlasnowolski, Michal, Michal Sadowski, Tymon Czarnota, et al. "3D-GNOME 2.0: a three-dimensional genome modeling engine for predicting structural variation-driven alterations of chromatin spatial structure in the human genome." Nucleic Acids Research 48, W1 (2020): W170—W176. http://dx.doi.org/10.1093/nar/gkaa388.

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Abstract Structural variants (SVs) that alter DNA sequence emerge as a driving force involved in the reorganisation of DNA spatial folding, thus affecting gene transcription. In this work, we describe an improved version of our integrated web service for structural modeling of three-dimensional genome (3D-GNOME), which now incorporates all types of SVs to model changes to the reference 3D conformation of chromatin. In 3D-GNOME 2.0, the default reference 3D genome structure is generated using ChIA-PET data from the GM12878 cell line and SVs data are sourced from the population-scale catalogue of SVs identified by the 1000 Genomes Consortium. However, users may also submit their own structural data to set a customized reference genome structure, and/or a custom input list of SVs. 3D-GNOME 2.0 provides novel tools to inspect, visualize and compare 3D models for regions that differ in terms of their linear genomic sequence. Contact diagrams are displayed to compare the reference 3D structure with the one altered by SVs. In our opinion, 3D-GNOME 2.0 is a unique online tool for modeling and analyzing conformational changes to the human genome induced by SVs across populations. It can be freely accessed at https://3dgnome.cent.uw.edu.pl/.
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Shepherd, Jeremiah J., Lingxi Zhou, William Arndt, Yan Zhang, W. Jim Zheng, and Jijun Tang. "Exploring genomes with a game engine." Faraday Discuss. 169 (2014): 443–53. http://dx.doi.org/10.1039/c3fd00152k.

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More and more evidence indicates that the 3D conformation of eukaryotic genomes is a critical part of genome function. However, due to the lack of accurate and reliable 3D genome structural data, this information is largely ignored and most of these studies have to use information systems that view the DNA in a linear structure. Visualizing genomes in real time 3D can give researchers more insight, but this is fraught with hardware limitations since each element contains vast amounts of information that cannot be processed on the fly. Using a game engine and sophisticated video game visualization techniques enables us to construct a multi-platform real-time 3D genome viewer. The game engine-based viewer achieves much better rendering speed and can handle much larger amounts of data compared to our previous implementation using OpenGL. Combining this viewer with 3D genome models from experimental data could provide unprecedented opportunities to gain insight into the conformation–function relationships of a genome.
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Poblete, Simón, and Horacio V. Guzman. "Structural 3D Domain Reconstruction of the RNA Genome from Viruses with Secondary Structure Models." Viruses 13, no. 8 (2021): 1555. http://dx.doi.org/10.3390/v13081555.

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Three-dimensional RNA domain reconstruction is important for the assembly, disassembly and delivery functionalities of a packed proteinaceus capsid. However, to date, the self-association of RNA molecules is still an open problem. Recent chemical probing reports provide, with high reliability, the secondary structure of diverse RNA ensembles, such as those of viral genomes. Here, we present a method for reconstructing the complete 3D structure of RNA genomes, which combines a coarse-grained model with a subdomain composition scheme to obtain the entire genome inside proteinaceus capsids based on secondary structures from experimental techniques. Despite the amount of sampling involved in the folded and also unfolded RNA molecules, advanced microscope techniques can provide points of anchoring, which enhance our model to include interactions between capsid pentamers and RNA subdomains. To test our method, we tackle the satellite tobacco mosaic virus (STMV) genome, which has been widely studied by both experimental and computational communities. We provide not only a methodology to structurally analyze the tertiary conformations of the RNA genome inside capsids, but a flexible platform that allows the easy implementation of features/descriptors coming from both theoretical and experimental approaches.
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Trieu, Tuan, and Jianlin Cheng. "3D genome structure modeling by Lorentzian objective function." Nucleic Acids Research 45, no. 3 (2016): 1049–58. http://dx.doi.org/10.1093/nar/gkw1155.

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Li, Chao, Xiao Dong, Haiwei Fan, Chuan Wang, Guohui Ding, and Yixue Li. "The 3DGD: a database of genome 3D structure." Bioinformatics 30, no. 11 (2014): 1640–42. http://dx.doi.org/10.1093/bioinformatics/btu081.

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Tjong, Harianto, Wenyuan Li, Reza Kalhor, et al. "Population-based 3D genome structure analysis reveals driving forces in spatial genome organization." Proceedings of the National Academy of Sciences 113, no. 12 (2016): E1663—E1672. http://dx.doi.org/10.1073/pnas.1512577113.

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Conformation capture technologies (e.g., Hi-C) chart physical interactions between chromatin regions on a genome-wide scale. However, the structural variability of the genome between cells poses a great challenge to interpreting ensemble-averaged Hi-C data, particularly for long-range and interchromosomal interactions. Here, we present a probabilistic approach for deconvoluting Hi-C data into a model population of distinct diploid 3D genome structures, which facilitates the detection of chromatin interactions likely to co-occur in individual cells. Our approach incorporates the stochastic nature of chromosome conformations and allows a detailed analysis of alternative chromatin structure states. For example, we predict and experimentally confirm the presence of large centromere clusters with distinct chromosome compositions varying between individual cells. The stability of these clusters varies greatly with their chromosome identities. We show that these chromosome-specific clusters can play a key role in the overall chromosome positioning in the nucleus and stabilizing specific chromatin interactions. By explicitly considering genome structural variability, our population-based method provides an important tool for revealing novel insights into the key factors shaping the spatial genome organization.
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Dissertationen zum Thema "3D genome structure"

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Mendieta, Esteban Julen 1992. "Chromatin 3D modelling from sparse 3C-based datasets." Doctoral thesis, Universitat Pompeu Fabra, 2020. http://hdl.handle.net/10803/670311.

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Genome spatial organisation and transcriptional activity are tightly coordinated to ensure the correct function of the cell. Thus, proper understanding of the chromatin organisation is needed to deepen into the processes regulating the activity of specific loci of interest. In this matter, Chromatin Conformation Capture (3C)-based technologies have helped to increase the understanding of the genomic interaction landscape. Particularly, sparse 3C technologies, like promoter capture Hi-C (pcHi-C), have focused on specific interactions of interest to unveil the interaction landscape associated with functional elements, like promoters. However, to properly characterize the sparse interaction profiles of pcHi-C, it is important to contextualize these interactions in a 3D perspective. Hence, in this thesis, we have developed a tool for the 3D modelling and analysis of sparse 3C-based datasets like pcHi-C, and we have probed its utility to help interpreting the regulatory architecture surrounding genes associated with cell-type or tissue-specific activ<br>La organización espacial del genoma y la actividad transcripcional están estrechamente coordinadas para garantizar el correcto funcionamiento de la célula. Por lo tanto, se necesita una comprensión adecuada de la organización de la cromatina para profundizar en los procesos que regulan la actividad de loci de interés. Tecnologías basadas en la captura de conformación de cromatina (3C) han facilitado la comprensión de la arquitectura genómica. Particularmente, las tecnologías 3C sparse, como promoter capture Hi-C (pcHi-C), se han centrado en interacciones especificas de interés para desvelar el panorama de interacción asociado con elementos funcionales como los promotores. Sin embargo, para comprender adecuadamente los perfiles sparse de interacción de pcHi-C, es importante contextualizar la perspectiva 3D que subyace a estas interacciones. En esta tesis, hemos desarrollado una herramienta para el modelado y análisis 3D de datos sparse derivados de 3C como pcHi-C, y hemos probado su utilidad en la comprensión de la arquitectura reguladora de genes asociados con una actividad especifica del tipo celular o tejido.
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Han, Chenggong. "Statistical models and computational methods for studying DNA differential methylation and 3D genome structure." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1595417277891892.

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Segueni, Julie. "DNA methylation changes CTCF binding and reorganizes 3D genome structure in breast cancer cells." Electronic Thesis or Diss., université Paris-Saclay, 2024. http://www.theses.fr/2024UPASL020.

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Les génomes des mammifères adoptent une organisation 3D fonctionnelle où les interactions entre les enhancers et les promoteurs des gènes sont contenues à l'intérieur de domaines d'association topologique (TADs). La protéine insulatrice CTCF a deux rôles dans ce processus : sa liaison aux promoteurs permettant la formation de boucles enhancers-promoteurs (structure intra-TAD) et sa liaison aux frontières des TADs empêchant la formation de boucles ectopiques entre domaines voisins. Surtout, les perturbations de la liaison de la protéine CTCF à des sites particuliers dans des cellules cancéreuses peuvent être dues à des changements de séquences d'ADN (mutations) ou à des changements de méthylation de l'ADN (épi-mutations). Nous avons d'abord réalisé des expériences calibrées de CTCF ChIP-seq et avons trouvé qu'un grand nombre de sites ont une liaison différente de CTCF, avec une grande fraction de sites différemment liés étant partagés parmi les lignées cancéreuses. Ces changements de liaison de CTCF peuvent être des gains ou des pertes de liaison et sont souvent situés près de gènes associés à la transformation cancéreuse. Nous avons trouvé une remarquable corrélation entre les changements de liaison de CTCF et les changements d'enrichissement de la marque H3K27ac, indiquant un lien entre la liaison de CTCF et l'activité d'éléments cis-régulateurs (CREs). Grâce à des expériences de Hi-C à haute résolution, nous avons évalué l'impact de ces changements de liaison de CTCF sur la structure de la chromatine, caractérisant une réorganisation considérable de la structure 3D du génome à des loci de gènes qui contiennent des pics CTCF perturbés. De manière inattendue, nous trouvons les exemples les plus drastiques de réorganisation à l'intérieur des TADs, au niveau des boucles enhancers-promoteurs. Ensuite, nous avons identifié les changements de méthylation de l'ADN comme la cause de la dérégulation de la liaison de CTCF dans notre modèle. En utilisant un agent retirant la méthylation de l'ADN sur l'ensemble du génome, nous avons réussi à partiellement inverser des changements de liaison de CTCF que nous avons observés et les changements d'expression induits. Ainsi, notre étude identifie une réorganisation invasive de la liaison de CTCF et des structures intra-TADs, induite par la méthylation de l'ADN. Ces épi-mutations récurrentes peuvent expliquer les mécanismes de dérégulation commune des gènes dans les cancers<br>Mammalian genomes adopt a functional 3D organization where enhancer-promoter interactions are constrained within Topologically Associating Domains (TADs). The CTCF insulator protein has a dual role in this process, with binding at promoters resulting in the formation of enhancer-promoter loops (intra-TAD structure) and binding at TAD boundaries preventing the formation of inappropriate loops between neighboring domains. Importantly, perturbations of CTCF binding at specific sites in cancer cells can be caused by both changes to the DNA sequence (mutations) or DNA methylation changes (epi-mutations). We first performed precisely-calibrated CTCF ChIP-seq experiments and found that a large number of sites are differentially bound, with a substantial fraction of differential CTCF binding peaks shared among cancer cell lines. Differential CTCF peaks can both be gained and lost and are often localized close to genes associated with breast cancer transformation. We found a striking correlation between CTCF binding changes and H3K27ac changes indicating a link between CTCF binding and the activity of cis-regulatory elements (CREs). Using high-resolution Hi-C, we assessed the impact of differential CTCF binding on chromatin structure, characterizing considerable 3D genome reorganization at gene loci with perturbed CTCF peaks. Unexpectedly, we find the most drastic examples of reorganization within TADs, at the level of enhancer-promoter loops. Then, we identified DNA methylation changes as the upstream cause of CTCF binding deregulation in our breast cancer model. Using genome-wide hypomethylating agent, we were able to partially reverse observed CTCF binding changes and the gene expression changes they induced. Our work thus identifies a pervasive DNA-methylation-guided reorganization of CTCF binding and intra-TAD structure. Such recurrent patterns of epi-mutations can provide a mechanistic explanation for shared gene deregulation in cancers
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Varoquaux, Nelle. "Inférence de la structure tri-dimensionnelle du génome." Thesis, Paris, ENMP, 2015. http://www.theses.fr/2015ENMP0059/document.

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La structure de l'ADN, des chromosomes et l'organisation du génome sont des sujets fascinants du monde de la biologie. La plupart de la recherche s'est concentrée sur la structure unidimensionnelle du génome, étudiant comment les gènes et les chromosomes sont organisés, et le lien entre l'organisation unidimensionnelle et la régulation des gènes, l'épissage, la méthylation… Cependant, le génome est avant tout organisé dans un espace euclidien tridimensionnel, et cette structure 3D, bien que moins étudiée, joue elle aussi un rôle important dans la fonction génomique de la cellule. La capture de la conformation des chromosomes (3C) et les méthodes qui en sont dérivées, associées au séquençage à haut débit (NGS) mesurent désormais en une seule expérience des interactions physiques entre paire de loci sur tout le génome, permettant ainsi aux chercheurs de découvrir les secrets de l'organisation des génomes. Ces nouvelles technologies ouvrent la voie à des études systématiques et globales sur le repliement de l'ADN dans le noyau. Cependant, ces nouvelles méthodes 3C, comme toute nouvelle technologie, sont accompagnées de nombreux défis computationnels et théoriques. Le premier chapitre est dédié au développement d'une méthode robuste et précise pour inférer un modèle tridimensionnel à partir de données Hi-C. Notre méthode modélise les fréquences d'interaction comme une distribution de Poisson dont l'intensité est une fonction de la distance euclidienne entre paires de loci : nous formulons ainsi l'inférence de la structure 3D comme un problème de maximum de vraisemblance. Nous montrons que notre méthode infère des modèles plus robustes et plus stables selon les données et les résolutions de celles-ci. Le deuxième chapitre est consacré à l'étude de l'architecture du P. falciparum, un petit parasite responsable de la forme la plus virulente et mortelle de la malaria. Ce projet, dont l'objectif était avant tout de répondre à une question biologique, cherchait à comprendre comment l'architecture 3D du génome du P. falciparum est liée à l'expression et la régulation des gènes à différent moments du cycle cellulaire du parasite. En collaboration avec les équipes de K. Le Roch et de W. Noble, spécialisées respectivement dans l'étude du P. falciparum, et dans le développement de méthode computationnelle pour étudier, entre autre, la structure 3D du génome, nous avons construit des modèles de l'organisation du génome à trois moments du cycle cellulaire du parasite. Ceux-ci révèlent que le génome est replié dans le noyau dans une structure complexe, où de nombreux éléments génomiques colocalisent : centromères, télomères… Cette architecture indique une forte association entre l'organisation spatiale du génome et l'expression des gènes. Le dernier chapitre répond à une question très différente, mais aussi liée à l'étude des données 3C. Celles-ci, initialement développées pour étudier la structure tridimensionnelle du génome, ont été récemment utilisées pour des applications très diverses : l'assemblage de génomes de novo, la déconvolution d'échantillons métagénomiques et l'annotation de génomes. Nous décrivons dans ce chapitre une nouvelle méthode, Centurion, qui infère conjointement la position de tous les centromères d'un organisme, en utilisant la propriété qu'ont les centromères à colocaliser dans le noyau. Cette méthode est donc une alternative aux méthodes de détection de centromères classiques, qui, malgré des années de recherche et un enjeu économique certain, n'ont pu identifier la position des centromères dans un certain nombre d'espèces de levure<br>The structure of DNA, chromosomes and genome organization is a topic that has fascinated the field of biology for many years. Most research focused on the one-dimensional structure of the genome, studying the linear organizations of genes and genomes and their link with gene expression and regulation, splicing, DNA methylation… Yet, spatial and temporal three-dimensional genome architecture is also thought to play an important role in many genomic functions. Chromosome conformation capture (3C) based methods, coupled with next generation sequencing (NGS), allow the measurement, in a single experiment, of genome wide physical interactions between pairs of loci, thus enabling to unravel the secrets behind 3D organization of genomes. These new technologies have paved the way towards a systematic and genome wide analysis of how DNA folds into the nucleus and opened new avenues to understanding many biological processes, such as gene regulation, DNA replication and repair, somatic copy number alterations and epigenetic changes. Yet, 3C technologies, as any new biotechnology, now poses important computational and theoretical challenges for which mathematically well grounded methods need to be developped. The first chapter is dedicated to developping a robust and accurate method to infer a 3D model of the genome from Hi-C data. Previous methods often formulated the inference as an optimization problem akin to multidimensional scaling (MDS) based on an ad hoc conversion of contact counts into euclidean wish distances. Chromosomes are modeled with a beads-on-a-string model, and the methods attempt to place the beads in a 3D euclidean space to fullfill a number of, often non convex, constraints and such that the pairwise distances between beads are as close as possible to the corresponding wish distances. These approaches rely on dubious hypotheses to convert contact counts into wish distances, challenging the accuracy of the final 3D model. Another limitation is the MDS formulation which is only intuitively motivated, and not grounded on a clear statistical model. To alleviate these problems, our method models contact counts as a Poisson distribution where the intensity is a decreasing function of the spatial distance between elements interacting. We then formulate the 3D structure inference as a maximum likelihood problem. We demonstrate that our method infers robust and stable models across resolutions and datasets. The second chapter focuses on the genome architecture of the P. falciparum, a small parasite responsible for the deadliest and most virulent form of human malaria. This project was biologically driven and aimed at understanding whether and how the 3D structure of the genome related to gene expression and regulation at different time points in the complex life cycle of the parasite. In collaboration with the Le Roch lab and the Noble lab, we built 3D models of the genome at three time points which resulted in a complex genome architecture indicative of a strong association between the spatial genome and gene expression. The last chapter tackles a very different question, also based on 3C-based data. Initially developped to probe the 3D architecture of the chromosomes, Hi-C and related techniques have recently been re-purposed for diverse applications: de novo genome assembly, deconvolution of metagenomic samples and genome annotations. We describe in this chapter a novel method, Centurion, that jointly infers the locations of all centromeres in a single yeast genome from Hi-C data, using the centromeres' tendency to strongly colocalize in the nucleus. Indeed, centromeres are essential for proper chromosome segregation, yet, despite extensive research, centromere locations are unknown for many yeast species. We demonstrate the robustness of our approach on datasets with low and high coverage on well annotated organisms. We then predict centromere coordinates for 6 yeast species that currently lack those annotations
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Svensson, Niclas. "Structure from Motion with Unstructured RGBD Data." Thesis, KTH, Skolan för elektroteknik och datavetenskap (EECS), 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-302553.

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This thesis covers the topic of depth- assisted Structure from Motion (SfM). When performing classic SfM, the goal is to reconstruct a 3D scene using only a set of unstructured RGB images. What is attempted to be achieved in this thesis is adding the depth dimension to the problem formulation, and consequently create a system that can receive a set of RGBD images. The problem has been addressed by modifying an already existing SfM pipeline and in particular, its Bundle Adjustment (BA) process. Comparisons between the modified framework and the baseline framework resulted in conclusions regarding the impact of the modifications. The results show mainly two things. First of all, the accuracy of the framework is increased in most situations. The difference is the most significant when the captured scene only is covered from a small sector. However, noisy data can cause the modified pipeline to decrease in performance. Secondly, the run time of the framework is significantly reduced. A discussion of how to modify other parts of the pipeline is covered in the conclusion of the report.<br>Följande examensarbete behandlar ämnet djupassisterad Struktur genom Rörelse (eng. SfM). Vid klassisk SfM är målet att återskapa en 3D scen, endast med hjälp av en sekvens av oordnade RGB bilder. I djupassiterad SfM adderas djupinformationen till problemformulering och följaktligen har ett system som kan motta RGBD bilder skapats. Problemet har lösts genom att modifiera en befintlig SfM- mjukvara och mer specifikt dess Buntjustering (eng. BA). Resultatet från den modifierade mjukvaran jämförs med resultatet av originalutgåvan för att dra slutsatser rådande modifikationens påverkan på prestandan. Resultaten visar huvudsakligen två saker. Först och främst, den modifierade mjukvaran producerar resultat med högre noggrannhet i de allra flesta fall. Skillnaden är som allra störst när bilderna är tagna från endast en liten sektor som omringar scenen. Data med brus kan dock försämra systemets prestanda aningen jämfört med orginalsystemet. För det andra, så minskar exekutionstiden betydligt. Slutligen diskuteras hur mjukvaran kan vidareutvecklas för att ytterligare förbättra resultaten.
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Votroubek, Lukáš. "Webový server pro predikci 3D struktury proteinu." Master's thesis, Vysoké učení technické v Brně. Fakulta informačních technologií, 2013. http://www.nusl.cz/ntk/nusl-236225.

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This work deals with proteins, especially with their structure and kinds of tertiary, or 3D, structure prediction. Tertiary structure prediction is very important for function prediction of this vitally important substance. Bioinformatics do this prediction much more effective and faster, because classical methods of structure prediction directly from molecule are very expensive and slow. On the other hand they are much more exact. Objective of this thesis is to describe tertiary structure prediction methods, describe used tools and possibility of automatic communication with them.  Next objective is describe implementation of server, that will serve to protein engineers for more effective finding of information about tertiary structure from more servers without requesting each of them separately. Results of testing will be described in this work too.
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Berselli, Michele. "Development and Application of Informatics Tools for the Detection and Analysis of Non-Canonical DNA Structures." Doctoral thesis, Università degli studi di Padova, 2018. http://hdl.handle.net/11577/3425749.

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The DNA is a flexible and heterogeneous molecule that can adopt different local conformations alternative to the classical double-helix. These noncanonical structures are known as non-B DNAs. These conformers appear to play an important role in different physiological and pathological cellular conditions and influence many biochemical properties of the genome. The formation of these structures is dependent upon specific features of the DNA sequence and different patterns may lead to the formation of different non-B DNAs. Due to lack of updated and flexible computational methods, during these years I focused my work on the development of new tools for the detection of some of these patterns at a genome-wide scale. Particularly, I focused on the detection of patterns that are degenerate. For this task, I developed NeSSie and QPARSE. NeSSie efficiently and exhaustively detects sequences with symmetrical properties, such as mirrors and palindromes that are associated to the formation of hairpins, cruciforms, and triple-stranded DNA. QPARSE detects consecutive exact or degenerate runs of Gs (G-islands) that are involved in the formation of G-quadruplex (G4) and paired G-quadruplex structures, i.e. two quadruplex structures that are close to each other along the sequence and that can fold cooperatively interacting into a higher-order structure. Eventually, I started using these tools to perform analyses on Mycobacterium spp. and human genomes. In the genomes of Mycobacterium spp. that are capable of developing tuberculosis-like diseases, NeSSie revealed the enrichment of a pattern with perfect mirror properties. Experimental analyses confirmed that the pattern can fold into a previously unknown but very stable hairpin structure. In the human genome, I focused on the detection of paired G-quadruplex systems. A genome-wide analysis revealed a striking enrichment of sequences potentially involved in the formation of paired G4 systems in correspondence of the TSS (Transcription Starting Site) of thousands of human genes. Among the predicted systems, one has been detected in correspondence of BCL2 TSS and ongoing experimental validations suggest a cooperative folding of the two G-quadruplex structures. These results contribute to the idea that non-B DNAs can play important functional and potentially structural roles. They also suggest that the folding landscape of the DNA molecule is much more complex than previously assumed, and we have a huge lack of knowledge towards the alternative structures that can form in DNA. Following these evidences, the DNA sequence needs to be widely re-evaluated considering also its structural properties addressing efforts both at computational and experimental validation levels.<br>La doppia elica del DNA è una molecola molto flessibile ed eterogenea, che può adottare una vasta gamma di conformazioni locali alternative. Queste conformazioni vengono collettivamente chiamate non-B DNA. Questi conformeri sembrano svolgere un ruolo importante in diverse condizioni cellulari sia fisiologiche che patologiche, ed influenzano molte proprietà biochimiche del genoma. La formazione di queste strutture dipende da caratteristiche specifiche della sequenza del DNA, e diversi motivi di sequenza possono portare alla formazione di diverse strutture non-B DNA. Durante questi anni, ho concentrato il mio lavoro sullo sviluppo di nuovi strumenti computazionali per la rilevazione di alcuni di questi motivi su scala genomica. Questo investimento di tempo è stato necessario, poiché attualmente mancano strumenti sufficientemente flessibili in grado di eseguire tali analisi. In particolare, mi sono concentrato sul rilevamento di motivi degenerati. A tale scopo, ho sviluppato NeSSie e QPARSE. NeSSie è in grado di rilevare in modo efficiente ed esauriente sequenze con proprietà simmetriche, come motivi speculari e palindromici associati alla formazione di forcine, strutture cruciformi e regioni di DNA a triplo filamento. QPARSE può rilevare ripetizioni consecutive di isole di G esatte o degenerate, che sono coinvolte nella formazione di G-quadruplex (G4) e strutture G-quadruplex appaiate (cioè due strutture quadruplex che si trovano vicine lungo la sequenza e che possono interagire formando una struttura di ordine superiore ed influenzandosi reciprocamente nel ripiegamento). Ho quindi iniziato a utilizzare questi strumenti per eseguire analisi su genomi appartenenti a specie di micobatterio e sul genoma umano. Nei genomi delle specie di micobatteri che sono in grado di sviluppare malattie simili alla tubercolosi, NeSSie ha rivelato l'arricchimento di un motivo con una perfetta simmetria a specchio. Analisi sperimentali hanno quindi confermato che questo motivo può piegarsi in una struttura a forcina precedentemente sconosciuta ma molto stabile. Nel genoma umano, mi sono concentrato sul rilevamento di sistemi G-quadruplex accoppiati. Una analisi su tutto il genoma ha rivelato un sorprendente arricchimento di sequenze potenzialmente coinvolte nella formazione di questi sistemi in corrispondenza del TSS (Sito di inizio della trascrizione) di migliaia di geni umani. Tra i sistemi predetti, uno identificato in corrispondenza del TSS di BCL2 è in corso di validazione sperimentale e i risultati preliminari sono promettenti. Questi risultati contribuiscono all'idea che i non-B DNA possano svolgere importanti ruoli funzionali e potenzialmente strutturali. Suggeriscono anche che il panorama di strutture che possono formarsi nella molecola di DNA sia molto più complesso di quanto ipotizzato, e che abbiamo ancora un'enorme mancanza di conoscenza verso queste strutture alternative. Seguendo queste evidenze, la sequenza del DNA deve essere ampiamente rivalutata non solo dal punto di vista della codifica, ma considerando anche le sue proprietà strutturali e funzionali. È quindi necessario indirizzare gli sforzi verso nuovi campi di indagine, studiando e caratterizzando queste strutture a livello genomico.
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Manoharan, Malini. "Genomic, structural and functional characterization of odorant binding proteins in olfaction of mosquitoes involved in infectious disease transmission." Phd thesis, Université de la Réunion, 2011. http://tel.archives-ouvertes.fr/tel-00979587.

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The role of odorant binding proteins in the olfaction of mosquitoes, the primary mechanism of human host recognition, has been an important focus of biological research in the field of infectious disease transmission by these insects. This thesis provides an in depth knowledge of these proteins in three mosquito species Anopheles gambiae, Aedes aegypti and Culex quinquefasciatus. A large scale analysis on these genomes has been carried out towards the identification of the odorant binding proteins in the mosquito genomes. Identification of many new OBP members, in particular in the Aedes aegypti and Culex quinquefasciatus species, and an extensive phylogenetic analysis presenting a novel classification of the OBP subfamilies of these mosquito species has been proposed. This results further demonstrates the extraordinary multiplicity and diversity of the OBP gene repertoire in these three mosquito genomes and highlights the striking sequence features that are nevertheless highly conserved across all mosquito OBPs. Owing to the availability of homologous structures from mosquitoes or related species, the 3D structure modelling of all the Classic OBPs from the three genomes (representing in total 137 structures) has been performed. This was completed by large scale docking studies on these structures by screening a large set of compounds that are known to be mosquito attractants or repellents. These provide many exciting new insights into the structural and functional aspects towards understanding the efficacy of some repellents and of some attractants from human emanations. Through molecular dynamics simulation, the structural changes observed in an OBP bounded to an odorant when pH conditions are modified were characterized and the probable mechanism of ligand binding and release is presented. This work provides the first insights to many of the long awaited questions on the genomic, structural and functional characterization of mosquito OBPs and can be viewed as a reliable starting point for further experimental research focussed on these aspects.
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Matala, Ilunga Benjamin. "Une correction à l’échelle et progressive des données Hi-C révèlent des principes fondamentaux de l’organisation tridimensionnelle et fonctionnelle du génome." Thèse, 2016. http://hdl.handle.net/1866/18662.

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Au cours des dernières années, de nouvelles évidences semblent indiquer que, tout autant que sa séquence, l’organisation d’un génome dans l’espace et le temps est importante pour comprendre la fonction de celui-ci. Une des avancées fonda- mentales sur le sujet a été de présenter à l’échelle du génome la carte des inter- actions ADN-ADN. Ces interactions sont essentiellement de 2 types, soit entre chromosomes ou entre régions du même chromosome. Par la suite, la modélisa- tion a permis de visualiser et appréhender la structure tridimensionnelle (3D) du génome à partir des données 3C, ou d’une modélisation purement théorique. Une question importante et centrale demeure, soit de résoudre les mécanismes res- ponsables de l’organisation spatiale et fonctionnelle du génome. Notamment, une question est de savoir comment des processus nucléaires tels que la transcription affectent la structure du génome. Cependant, l’idée selon laquelle les données de types 3C capturent cette information dans la levure est remise en question par le fait que les modèles théoriques du génome récapitulent les caractéristiques mar- quantes soulignées par 3C. Pour répondre à cette question, nous avons conçu une approche qui, pour évaluer l’importance d’une interaction, se base sur la distri- bution d’interactions entre les 2 régions d’ADN mises en contacts. Nos résultats supportent l’hypothèse selon laquelle les éléments fonctionnels et propres aux données expérimentales de la structure 3D du génome se forment d’une manière spécifique à l’échelle de l’interaction et au type d’interactions. Par ailleurs, nos résultats indiquent qu’un grand nombre de facteurs de transcription induisent la proximité spatiale des gènes dont ils régulent l’expression.<br>Over the last decade, accumulating empirical evidence suggest that, as much as its sequence, a genome spatiotemporal organization is essential to understand it’s biological function. One of the major breakthroughs has been chromosome conformation capture (3C) experiments presenting DNA-DNA contact for whole genomes at unprecedented resolution (5-10kb). Along with genome-wide maps of DNA contacts came genome 3D modelling from experimental 3C data, and even from purely theoretical and biophysical basis. However, the mechanisms underlying the regulation of the genome spatial functional organization are still not well understood. Among other questions, how the regulation and event of nuclear processes such as transcription modulate genome structure or how genome structure affect these in turn is still not fully resolved. Moreover, computational models of S.cerevisae genome have recapitulated the hallmarks at larger scale of its 3D features. In order to contrast genome structural features arising from the event of biochemical and molecular activity, we have develop a method assessing the significance of structural features. The underlying principle is to consider for a given interaction, the two DNA regions put in contact and the distribution of existing interactions between these before assigning significance to the selected interaction. Using this method, we demonstrate that structural features resulting from potential biochemically active processes occur at precise scale on the genome. Our results also highlight that exact nature of the interaction (between vs across chromosomes) is crucial to such events. Finally, we have also found that a large portion of transcription factors have their targeted genes in spatial proximity.
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Bücher zum Thema "3D genome structure"

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Tiana, Guido, and Luca Giorgetti. Modeling the 3D Conformation of Genomes. Taylor & Francis Group, 2019.

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Tiana, Guido, and Luca Giorgetti. Modeling the 3D Conformation of Genomes. Taylor & Francis Group, 2019.

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The connection of brains theory: Brain,brain waves,mind,physiology of brain,cosmic memory,humanaly memory,unlimited memory,limited memory,limbic system,thalamus,hypothalamus,midbrain,cortex, cerebral cortex, cerebral cortex ,cerebellum,cerebellar cortex,neuron,neurons,gray neurons,white neuronal,CNS,think,thoughts,Nervous system,Monkey brain,Brain Animals,Animal memory,central nervous system,smart energy,intelligent energy, intelligence creation,smartness animals,physiology of thinking,the cosmic memory,thinking system,limbic system, the cerebral cortex, brain waves, Humanaly understanding, universal memory, five senses, experiences, Human Magical Talent, book "Human Magical Talent", empirical understanding, the Spherical shape of the head,Walking on two legs, structural differences of the skull, genotype of cortical neurons, cortical neurons, past experiences, see, hear, touch, Clever behaviors, up the cortical lobes of the brain, cortical lobes, cortical lobes of the brain, Fornal lobe, planning and decisions, , planning, decisions, temporal lobe, occipital lobe, deeper parts of the brain, deep processing, brain through, genetics, phenotype,genotype, the cortical lobes, cortical lobes, HMT theory, HMT, communication of brains theory, 2% difference of the genome of brain neurons, The spherical shape of the human head, grooves of the brain, grooves, Neocortex neurons, Neocortex, brain grooves, brain proteins, catecholamines, mental habits, human cognitive abilities ,mental experience , dream, Sensory receptors, Dendrit , dendritic spines, motor neurons, hippocampus, sensory dendrites, meaningful electrical pulses, brain reactions, experiences received, shape of the brain(3D oval mode), dendritic branches , brain satellite dish full of grooves, pyramidal neurons of the neocortex , Purkinje neurons, fantastic brain, fantastic mind, grooves on the surface of the brain, grooves in the cortex, mammalian brain, cognitive abilities, human brain neurons, creativity determine, animal creativity, HMT talent, Creativity in humans, science of psychology, psychology, The idea of HMT, negative thoughts, Mental Experience, the connection of the brain to cosmic memory,koorosh behzad,. archive.org publisher, 2022.

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Buchteile zum Thema "3D genome structure"

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Polles, Guido, Nan Hua, Asli Yildirim, and Frank Alber. "Genome Structure Calculation through Comprehensive Data Integration." In Modeling the 3D Conformation of Genomes. CRC Press, 2019. http://dx.doi.org/10.1201/9781315144009-11.

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Casadio, R., P. Fariselli, P. L. Martelli, A. Pierleoni, I. Rossi, and G. von Heijne. "The state of the art of membrane protein structure prediction: from sequence to 3D structure." In Modern Genome Annotation. Springer Vienna, 2008. http://dx.doi.org/10.1007/978-3-211-75123-7_15.

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Ivanisenko, V. A., S. S. Pintus, D. A. Grigorovich, L. N. Ivanisenko, V. A. Debelov, and A. M. Matsokin. "PDBSiteScan: A Program Searching for Functional Sites in Protein 3D Structures." In Bioinformatics of Genome Regulation and Structure. Springer US, 2004. http://dx.doi.org/10.1007/978-1-4419-7152-4_20.

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Papale, Andrea, and Angelo Rvosay. "Structure and Microrheology of Genome Organization: From Experiments to Physical Modeling." In Modeling the 3D Conformation of Genomes. CRC Press, 2019. http://dx.doi.org/10.1201/9781315144009-7.

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Paro, Renato, Ueli Grossniklaus, Raffaella Santoro, and Anton Wutz. "Biology of Chromatin." In Introduction to Epigenetics. Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-68670-3_1.

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AbstractThis chapter provides an introduction to chromatin. We will examine the organization of the genome into a nucleosomal structure. DNA is wrapped around a globular complex of 8 core histone proteins, two of each histone H2A, H2B, H3, and H4. This nucleosomal arrangement is the context in which information can be established along the sequence of the DNA for regulating different aspects of the chromosome, including transcription, DNA replication and repair processes, recombination, kinetochore function, and telomere function. Posttranslational modifications of histone proteins and modifications of DNA bases underlie chromatin-based epigenetic regulation. Enzymes that catalyze histone modifications are considered writers. Conceptually, erasers remove these modifications, and readers are proteins binding these modifications and can target specific functions. On a larger scale, the 3-dimensional (3D) organization of chromatin in the nucleus also contributes to gene regulation. Whereas chromosomes are condensed during mitosis and segregated during cell division, they occupy discrete volumes called chromosome territories during interphase. Looping or folding of DNA can bring regulatory elements including enhancers close to gene promoters. Recent techniques facilitate understanding of 3D contacts at high resolution. Lastly, chromatin is dynamic and changes in histone occupancy, histone modifications, and accessibility of DNA contribute to epigenetic regulation.
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Wang, Yubo, Yanlin Feng, Deyan Wang, and Tao Ma. "Structural Variations and 3D Structure of the Populus Genus." In Compendium of Plant Genomes. Springer International Publishing, 2024. http://dx.doi.org/10.1007/978-3-031-50787-8_2.

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Benedetti, Fabrizio, Dusan Racko, Julien Dorier, and Andrzej Stasiak. "Introducing Supercoiling into Models of Chromosome Structure." In Modeling the 3D Conformation of Genomes. CRC Press, 2019. http://dx.doi.org/10.1201/9781315144009-6.

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Gherardi, Marco, Vittore Scolari, Remus Thei Dame, and Marco Cosentino Lagomarsino. "Chromosome Structure and Dynamics in Bacteria: Theory and Experiments." In Modeling the 3D Conformation of Genomes. CRC Press, 2019. http://dx.doi.org/10.1201/9781315144009-9.

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Bhowmick, Biplab Kumar. "Possibility of Uncoding Structural Organization of Genome in Rice Research: Prospects and Approaches by 3D Genome Sequencing." In Applications of Bioinformatics in Rice Research. Springer Singapore, 2021. http://dx.doi.org/10.1007/978-981-16-3997-5_1.

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Sætre, Glenn-Peter, and Mark Ravinet. "Sequencing the genome and beyond." In Evolutionary Genetics. Oxford University Press, 2019. http://dx.doi.org/10.1093/oso/9780198830917.003.0010.

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Science is defined by continual progress and new technologies. This final chapter starts with introducing what it means to sequence and assemble a reference genome. It is easy to forget that the true genome is not linear but has structure and function. In this chapter the genome is explored as a 3D entity—from how it is transcribed, to how proteins interact with it, and finally to how it is actually structured. This also gives an opportunity to focus on epigenetics and how to interpret processes such as DNA methylation in an evolutionary context. The second part of the chapter focuses on ways we can interact with the genome—exploring how we might test the function and role that candidate genes play. The chapter introduces transgenics, in particular the transformative technology of CRISPR/CAS9, and explores how this might change the face of evolutionary biology in the near future.
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Konferenzberichte zum Thema "3D genome structure"

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"3D-,odels creation based on solid tumor." In Bioinformatics of Genome Regulation and Structure/ Systems Biology. institute of cytology and genetics siberian branch of the russian academy of science, Novosibirsk State University, 2020. http://dx.doi.org/10.18699/bgrs/sb-2020-311.

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Trieu, Tuan, and Jianlin Cheng. "3D Genome Structure Modeling by Lorentzian Objective Function." In BCB '17: 8th ACM International Conference on Bioinformatics, Computational Biology, and Health Informatics. ACM, 2017. http://dx.doi.org/10.1145/3107411.3107455.

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"Simulating of 3D genome data with predefined chromosomal rearrangements." In Bioinformatics of Genome Regulation and Structure/Systems Biology (BGRS/SB-2022) :. Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of Sciences, 2022. http://dx.doi.org/10.18699/sbb-2022-062.

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"Insights into the 3D-genome organization in malaria mosquitoes." In Bioinformatics of Genome Regulation and Structure/Systems Biology (BGRS/SB-2022) :. Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of Sciences, 2022. http://dx.doi.org/10.18699/sbb-2022-059.

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"3D-2 heterogeneous breast cancer models." In Bioinformatics of Genome Regulation and Structure/Systems Biology (BGRS/SB-2022) :. Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of Sciences, 2022. http://dx.doi.org/10.18699/sbb-2022-489.

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"Laser 3D-modeling in research of molecular features of skin lymphatic vessels in the patients with urticaria pigmentosa." In Bioinformatics of Genome Regulation and Structure/ Systems Biology. institute of cytology and genetics siberian branch of the russian academy of science, Novosibirsk State University, 2020. http://dx.doi.org/10.18699/bgrs/sb-2020-296.

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"Multi-class abdominal aortic aneurysm segmentation via 3D neural networks." In Bioinformatics of Genome Regulation and Structure/Systems Biology (BGRS/SB-2022) :. Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of Sciences, 2022. http://dx.doi.org/10.18699/sbb-2022-674.

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"Processing of serial microscopic images for 3D reconstruction of plant tissues." In Bioinformatics of Genome Regulation and Structure/Systems Biology (BGRS/SB-2022) :. Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of Sciences, 2022. http://dx.doi.org/10.18699/sbb-2022-375.

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"Autophagy activation in 3D-spheroid leads to the mesenchymal stem cells rejuvenation." In Bioinformatics of Genome Regulation and Structure/Systems Biology (BGRS/SB-2022) :. Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of Sciences, 2022. http://dx.doi.org/10.18699/sbb-2022-623.

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"804 BGRS/SB-2022 Artificial intelligence (AI) of 3D MRI images for neurooncology." In Bioinformatics of Genome Regulation and Structure/Systems Biology (BGRS/SB-2022) :. Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of Sciences, 2022. http://dx.doi.org/10.18699/sbb-2022-466.

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Berichte der Organisationen zum Thema "3D genome structure"

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Rafaeli, Ada, Russell Jurenka, and Chris Sander. Molecular characterisation of PBAN-receptors: a basis for the development and screening of antagonists against Pheromone biosynthesis in moth pest species. United States Department of Agriculture, 2008. http://dx.doi.org/10.32747/2008.7695862.bard.

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The original objectives of the approved proposal included: (a) The determination of species- and tissue-specificity of the PBAN-R; (b) the elucidation of the role of juvenile hormone in gene regulation of the PBAN-R; (c) the identificationof the ligand binding domains in the PBAN-R and (d) the development of efficient screening assays in order to screen potential antagonists that will block the PBAN-R. Background to the topic: Moths constitute one of the major groups of pest insects in agriculture and their reproductive behavior is dependent on chemical communication. Sex-pheromone blends are utilised by a variety of moth species to attract conspecific mates. In most of the moth species sex-pheromone biosynthesis is under circadian control by the neurohormone, PBAN (pheromone-biosynthesis-activating neuropeptide). In order to devise ideal strategies for mating disruption/prevention, we proposed to study the interactions between PBAN and its membrane-bound receptor in order to devise potential antagonists. Major conclusions: Within the framework of the planned objectives we have confirmed the similarities between the two Helicoverpa species: armigera and zea. Receptor sequences of the two Helicoverpa spp. are 98% identical with most changes taking place in the C-terminal. Our findings indicate that PBAN or PBAN-like receptors are also present in the neural tissues and may represent a neurotransmitter-like function for PBAN-like peptides. Surprisingly the gene encoding the PBAN-receptor was also present in the male homologous tissue, but it is absent at the protein level. The presence of the receptor (at the gene- and protein-levels), and the subsequent pheromonotropic activity are age-dependent and up-regulated by Juvenile Hormone in pharate females but down-regulated by Juvenile Hormone in adult females. Lower levels of pheromonotropic activity were observed when challenged with pyrokinin-like peptides than with HezPBAN as ligand. A model of the 3D structure of the receptor was created using the X-ray structure of rhodopsin as a template after sequence alignment of the HezPBAN-R with several other GPCRs and computer simulated docking with the model predicted putative binding sites. Using in silico mutagenesis the predicted docking model was validated with experimental data obtained from expressed chimera receptors in Sf9 cells created by exchanging between the three extracellular loops of the HezPBAN-R and the Drosophila Pyrokinin-R (CG9918). The chimera receptors also indicated that the 3ʳᵈ extracellular loop is important for recognition of PBAN or Diapause hormone ligands. Implications: The project has successfully completed all the objectives and we are now in a position to be able to design and screen potential antagonists for pheromone production. The successful docking simulation-experiments encourage the use of in silico experiments for initial (high-throughput) screening of potential antagonists. However, the differential responses between the expressed receptor (Sf9 cells) and the endogenous receptor (pheromone glands) emphasize the importance of assaying lead compounds using several alternative bioassays (at the cellular, tissue and organism levels). The surprising discovery of the presence of the gene encoding the PBAN-R in the male homologous tissue, but its absence at the protein level, launches opportunities for studying molecular regulation pathways and the evolution of these GPCRs. Overall this research will advance research towards the goal of finding antagonists for this important class of receptors that might encompass a variety of essential insect functions.
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