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Author: Przemysław Szałaj (Doctor of Sciences: Statistics)
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Languages : nl
Pages : 0
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Author: Przemysław Szałaj (Doctor of Sciences: Statistics)
Publisher:
ISBN:
Category :
Languages : nl
Pages : 0
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Author: Przemyslaw Szalaj
Publisher:
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Category :
Languages : en
Pages : 45
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Author: Karim Mekhail
Publisher: Frontiers Media SA
ISBN: 288974504X
Category : Science
Languages : en
Pages : 139
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Author: Guido Tiana
Publisher: CRC Press
ISBN: 1351386999
Category : Science
Languages : en
Pages : 319
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This book provides a timely summary of physical modeling approaches applied to biological datasets that describe conformational properties of chromosomes in the cell nucleus. Chapters explain how to convert raw experimental data into 3D conformations, and how to use models to better understand biophysical mechanisms that control chromosome conformation. The coverage ranges from introductory chapters to modeling aspects related to polymer physics, and data-driven models for genomic domains, the entire human genome, epigenome folding, chromosome structure and dynamics, and predicting 3D genome structure.
Author: Anastasiya Belyaeva
Publisher:
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Languages : en
Pages :
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Biological processes from differentiation to disease progression are governed by gene regulatory mechanisms. Currently large-scale omics and imaging data sets are being collected to characterize gene regulation at every level. Such data sets present new opportunities and challenges for extracting biological insights and elucidating the gene regulatory logic of cells. In this thesis, I present computational methods for the analysis and integration of various data types used for cell profiling. Specifically, I focus on analyzing and linking gene expression with the 3D organization of the genome. First, I describe methodologies for elucidating gene regulatory mechanisms by considering multiple data modalities. I design a computational framework for identifying colocalized and coregulated chromosome regions by integrating gene expression and epigenetic marks with 3D interactions using network analysis. Then, I provide a general framework for data integration using autoencoders and apply it for the integration and translation between gene expression and chromatin images of naive T-cells. Second, I describe methods for analyzing single modalities such as contact frequency data, which measures the spatial organization of the genome, and gene expression data. Given the important role of the 3D genome organization in gene regulation, I present a methodology for reconstructing the 3D diploid conformation of the genome from contact frequency data. Given the ubiquity of gene expression data and the recent advances in single-cell RNA-sequencing technologies as well as the need for causal modeling of gene regulatory mechanisms, I then describe an algorithm as well as a software tool, difference causal inference (DCI), for learning causal gene regulatory networks from gene expression data. DCI addresses the problem of directly learning differences between causal gene regulatory networks given gene expression data from two related conditions. Finally, I shift my focus from basic biology to drug discovery. Given the current COVID19 pandemic, I present a computational drug repurposing platform that enables the identification of FDA approved compounds for drug repurposing and investigation of potential causal drug mechanisms. This framework relies on identifying drugs that reverse the signature of the infection in the space learned by an autoencoder and then uses causal inference to identify putative drug mechanisms.
Author: Tom Sexton
Publisher: Springer Nature
ISBN: 1071624970
Category : Science
Languages : en
Pages : 332
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This detailed volume explores a variety of cutting-edge techniques used to interrogate spatial genome organization. Beginning with a section covering the vital chromosome conformation capture (3C) technique, this collection continues with chapters on targeted Hi-C approaches, sequencing-based approaches to assess nuclear environment, as well as single-cell technologies to better characterize the heterogeneity and dynamics of nuclear architectures and approaches to visualize them by microscopy. Finally, in order to be able to ask functional questions about the role of spatial chromatin organization in genomic control, the last section provides methods for acute manipulations of chromatin architecture. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Spatial Genome Organization: Methods and Protocols is an ideal resource for researchers searching for the best techniques to address their own specific research questions.
Author: Yifeng Qi (Scientist in chemistry)
Publisher:
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Languages : en
Pages : 0
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This thesis is organized as follows. In the first chapter, we introduce a computational model to simulate chromatin structure and dynamics. The model defines chromatin states by taking one-dimensional genomics and epigenomics data as input and quantitatively learns interacting patterns between these states using experimental contact data. Once learned, the model is able to make de novo predictions of 3D chromatin structures at five-kilo-base resolution across different cell types. The manuscript associated with this study is published in PLoS Computational Biology, 15.6, e1007024 (2019).
Author: Narasimha Marella
Publisher:
ISBN:
Category :
Languages : en
Pages : 203
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The mammalian genome is housed in a membrane bound organelle referred to as the nucleus. The three dimensional structural organization of the nucleus has been implicated to affect various genomic functions. Each chromosome in the interphase cell nuclei occupies a distinct region called the chromosome territory. Advances in cytogenetic techniques including fluorescence insitu hybridization and development of chromosome specific probes have allowed visualization of these individual territories within the interphase nuclei. The organization of the chromosome territories within the nuclear environment is highly debatable as it seems to be influenced by chromosome size or by gene density. Changes in the spatial organization of the chromosomes during differentiation and conservation of territorial associations within various tissue and cell types are also less understood aspects of genomic organization.^It is known that aberrations in the spatial and temporal organization of the genome leads to expression of disease phenotypes like cancer. However this phenomenon has been exemplified in only a few studies. In order to provide a deeper understanding of the above mentioned aspects of spatial genomic organization and its influence on gene regulation we have performed chromosome territory labeling experiments on a subset of six human chromosomes by adopting a RE-FISH (repeated fluorescence insitu hybridization) in a normal diploid human fibroblast (WI38) and a normal breast epithelial (MCF10A) cell line. We identified a tissue specific organization for these chromosomes within each of these cell lines by employing a novel computer graphing algorithm referred to as the generalized median graph (GMG). The radial positioning of the chromosomes showed a linear correlation with the chromosome size in both cell lines.^We were also able to measure the chromosome-chromosome associations for our subset of chromosomes using in house developed algorithms (Chapter 2). Our study on chromosome 18 and 19 organization during keratinocyte differentiation suggests significant stage specific shifts in chromosome territory spatial positions during differentiation (Chapter 3). We further extended our investigations on genome organization from chromosome territories to individual genes. FISH experiments were performed with individual cosmid probes as well as BAC probes to elucidate the organization of the human type I interferon gene cluster on metaphase chromosomes of the human osteosarcoma cell line (MG63) and normal diploid fibroblasts (Chapter 4). Both the cosmid and BAC probes consistently showed a six fold ladder-like genomic amplification of the interferon gene cluster on one chromosome in the MG63 cell line termed the `interferon chromosome'. This amplification was absent on WI38 metaphase chromosomes.^Comparative genomic hybridization (CGH) analysis also confirmed this gene amplification. We also found that centromere and whole chromosome regions of chromosomes 4 and 9 were interspersed with the amplified gene cluster on the interferon chromosome. Based on the results of our study, we propose a model involving the breakage- fusion -bridge theory for the generation of the interferon chromosome in the MG63 cell line (Chapter 4). Finally in this thesis, we investigate the relationship of alterations in spatial organization and genomic amplification to aberrant changes in gene expression in cancer. The MCF10A series of breast epithelial cell lines consisting of a normal MCF10A, premalignant MCF10At1 and malignant MCF10CA1a were utilized in these studies. Spectral Karyotyping (SKY) and CGH analyses were performed on all three cell lines. Two color gene expression analyses were carried out on mRNA isolated from normal MCF10A and malignant MCF10CA1a cell lines.^A total of 8000 genes were identified that showed at least two fold changes- either up or down regulated. Structural changes observed by CGH and SKY were correlated with the gene expression changes. Our results showed that a direct correlation between modifications in genomic structure and changes in gene expression does not exist in a majority of the observed genes (Chapter 5). Overall, the experiments done in this thesis highlight and explore the relationships between the spatial and temporal organization in the nucleus and its influence on genomic function.^The thesis is divided into the following six chapters:Chapter1: IntroductionChapter 2: Tissue specific chromosome organization in normal and cancer cell nuclei Chapter 3: Distinct changes in chromosome arrangements during human epidermal keratinocyte differentiation Chapter 4: Ladder-like amplification of the type I interferon gene cluster in the human osteosarcoma cell line MG63Chapter 5: Cytogenetic and functional analysis of breast cancer progression: Integration of spectral karyotyping, comparative genomic hybridization and cDNA microarray approachesChapter 6: Future Aims.
Author: Scott Camazine
Publisher: Princeton University Press
ISBN: 0691212929
Category : Science
Languages : en
Pages :
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The synchronized flashing of fireflies at night. The spiraling patterns of an aggregating slime mold. The anastomosing network of army-ant trails. The coordinated movements of a school of fish. Researchers are finding in such patterns--phenomena that have fascinated naturalists for centuries--a fertile new approach to understanding biological systems: the study of self-organization. This book, a primer on self-organization in biological systems for students and other enthusiasts, introduces readers to the basic concepts and tools for studying self-organization and then examines numerous examples of self-organization in the natural world. Self-organization refers to diverse pattern formation processes in the physical and biological world, from sand grains assembling into rippled dunes to cells combining to create highly structured tissues to individual insects working to create sophisticated societies. What these diverse systems hold in common is the proximate means by which they acquire order and structure. In self-organizing systems, pattern at the global level emerges solely from interactions among lower-level components. Remarkably, even very complex structures result from the iteration of surprisingly simple behaviors performed by individuals relying on only local information. This striking conclusion suggests important lines of inquiry: To what degree is environmental rather than individual complexity responsible for group complexity? To what extent have widely differing organisms adopted similar, convergent strategies of pattern formation? How, specifically, has natural selection determined the rules governing interactions within biological systems? Broad in scope, thorough yet accessible, this book is a self-contained introduction to self-organization and complexity in biology--a field of study at the forefront of life sciences research.
Author: Max Garrett Kushner
Publisher:
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Languages : en
Pages : 0
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Gene expression is regulated by a number of different mechanisms, but of particular interest recently is the regulation of gene expression through spatial organization of the genome. Various techniques have been developed and continue to be developed to further characterize and study the dependence of transcriptional regulation on genome organization. In this dissertation, I will discuss a series of projects aimed at designing a novel method to examine the relationship between transcriptional activity and genomic contacts.I will discuss efforts to characterize photoactivatable compounds including members of the psoralen family for use as a tool to examine genomic contacts. I will explain the determination of many different photochemical properties of psoralen compounds. I will also mention optimization and the use of psoralen compounds with two-photon excitation. Here I present a technique we call Femto-Seq. This technique utilizes a photoactivatable DNA crosslinking compound with an affinity tag to take a snapshot of the DNA sequences spatially around a genomic locus of interest. After allowing the photoactivatable compound to intercalate, two-photon excitation is used to covalently bind sequences in a nuclear volume of interest (around a fluorescently labeled gene for example). The affinity tag on the crosslinker is used to enrich for sequences from the irradiated volume which are then analyzed through sequencing. I will present pilot experiments designed to examine the efficacy of such a method by looking at the enrichment of a targeted transgene. We report a 15-fold enrichment of the transgene matching expected enrichment based on the nuclear volume of interest. I will describe potential applications and extensions of such a technique. Many parts of the Femto-Seq method can be further optimized. Since the technique involves fluorescently labeling a genomic locus of interest, fluorescently labeled engineerable DNA binding proteins are particularly valuable. While many exist, we were particularly interested in Transcription Activator Like Effectors (TALEs). In order to understand the mechanisms of TALE binding we utilized a variety of techniques including DNA curtains, single molecule co-localization and Fluorescent Correlation Spectroscopy. I will also discuss the potential use of microfluidic platforms to increase throughput of the pulldown and cleanup processes.
