Computational Methods For Analyzing And Modeling Gene Regulation And 3d Genome Organization
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Computational Methods for Analyzing and Modeling Gene Regulation and 3D Genome Organization
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.
Computational Methods for 3D Genome Analysis
This volume covers the latest methods and analytical approaches used to study the computational analysis of three-dimensional (3D) genome structure. The chapters in this book are organized into six parts. Part One discusses different NGS assays and the regulatory mechanism of 3D genome folding by SMC complexes. Part Two presents analysis workflows for Hi-C and Micro-C in different species, including human, mouse, medaka, yeast, and prokaryotes. Part Three covers methods for chromatin loop detection, sub-compartment detection, and 3D feature visualization. Part Four explores single-cell Hi-C and the cell-to-cell variability of the dynamic 3D structure. Parts Five talks about the analysis of polymer modelling to simulate the dynamic behavior of the 3D genome structure, and Part Six looks at 3D structure analysis using other omics data, including prediction of 3D genome structure from the epigenome, double-strand break-associated structure, and imaging-based 3D analysis using seqFISH. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and tools, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, Computational Methods for 3D Genome Analysis: Methods and Protocols is a valuable resource for researchers interested in using computational methods to further their studies in the nature of 3D genome organization.
Computational Methods for the Analysis of Genomic Data and Biological Processes
In recent decades, new technologies have made remarkable progress in helping to understand biological systems. Rapid advances in genomic profiling techniques such as microarrays or high-performance sequencing have brought new opportunities and challenges in the fields of computational biology and bioinformatics. Such genetic sequencing techniques allow large amounts of data to be produced, whose analysis and cross-integration could provide a complete view of organisms. As a result, it is necessary to develop new techniques and algorithms that carry out an analysis of these data with reliability and efficiency. This Special Issue collected the latest advances in the field of computational methods for the analysis of gene expression data, and, in particular, the modeling of biological processes. Here we present eleven works selected to be published in this Special Issue due to their interest, quality, and originality.