Integrative Multi-Modal, Multi-Omics Analytics for the Better Understanding of Metabolic Diseases PDF Download
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Author: Animesh Acharjee
Publisher: Frontiers Media SA
ISBN: 283253550X
Category : Medical
Languages : en
Pages : 135
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Book Description
Author: Animesh Acharjee
Publisher: Frontiers Media SA
ISBN: 283253550X
Category : Medical
Languages : en
Pages : 135
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Book Description
Author: Thorsten Joachims
Publisher: Springer Science & Business Media
ISBN: 1461509076
Category : Computers
Languages : en
Pages : 218
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Book Description
Based on ideas from Support Vector Machines (SVMs), Learning To Classify Text Using Support Vector Machines presents a new approach to generating text classifiers from examples. The approach combines high performance and efficiency with theoretical understanding and improved robustness. In particular, it is highly effective without greedy heuristic components. The SVM approach is computationally efficient in training and classification, and it comes with a learning theory that can guide real-world applications. Learning To Classify Text Using Support Vector Machines gives a complete and detailed description of the SVM approach to learning text classifiers, including training algorithms, transductive text classification, efficient performance estimation, and a statistical learning model of text classification. In addition, it includes an overview of the field of text classification, making it self-contained even for newcomers to the field. This book gives a concise introduction to SVMs for pattern recognition, and it includes a detailed description of how to formulate text-classification tasks for machine learning.
Author: Debolina Sarkar
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Rapid progress in high-throughput experimental technologies has enabled generation of large-scale systems biology datasets. These span all biological hierarchies from genomics describing the genetic make-up, transcriptomics and proteomics at the gene and enzyme expression level, metabolomics that helps quantify the amount and nature of resultant biomolecules, to finally phenomics that describes the overall traits of an individual. This veritable data deluge necessitates algorithmic and computational advances that can leverage multi-omics integration, in order to facilitate the analysis of complex systems and extract meaningful insights. Flux balance analysis (FBA) using genome-scale metabolic (GSM) models provide an advantageous platform for doing so as these models are (relatively) parameter-free, can be constructed using the annotated genome alone and simulated in linear time offering scale-up benefits. GSMs model a network view of metabolism, wherein metabolites are cast as nodes in a graph linked via edges representing all possible biochemical conversions occurring within an organism. In Chapter 1, we present an overview of constraints-based analysis of metabolic networks, including the reconstruction of GSM models, their use within an optimization-based scheme such as FBA, and the various applications of such models. Next, we describe the extension of metabolic modeling frameworks, originally designed for microbial systems, to the study of plants. This is accompanied by its own set of challenges, such as accurately capturing the division of roles between the various tissue and organ systems and dealing with systematic biases that are typically associated with poorly annotated non-model systems. Finally, we explore how the incorporation of new data types, modeling schemes, and computational tools have impacted FBA by helping increase its predictive power and scope. FBA has proven to be quite adept at describing aggregated metabolite flows, i.e., providing a snapshot of metabolism as averaged over the entire growth cycle. However, it is also time invariant, and thus does not accommodate temporally varying cell processes such as sequestering different biomass components at various time points in a growth cycle However, we know from experiments that many organisms including cyanobacteria have a lifestyle that is heavily tailored around light availability and thus show metabolic oscillations. In Chapter 2, we present a framework called CycleSyn that augments FBA by accounting for such temporal trends. CycleSyn discretizes a growth cycle into individual time periods (called Time Point Models or TPMs), each described by its own GSM model. The flow of metabolites across TPMs is allowed while inventorying metabolite levels and only allowing for the utilization of currently or previously produced compounds. Additional time-dependent constraints can also be imposed to capture the cyclic nature of cellular processes. CycleSyn was used to develop a diurnal FBA model of Synechocystis sp. PCC 6803 metabolism. Predicted flux and metabolite pools were in line with published studies, paving the way for constructing time-resolved GSM models. Additionally, the metabolic reorganization that would be required to enable Synechocystis PCC 6803 to fix nitrogen by temporally separating it from photosynthesis was also explored. Similar to modeling multiple metabolic models at once in CycleSyn, in Chapter 3 we extend this to modeling multiple organisms together as in a community, so as to discern the underlying interactions. This community comprised a genetically streamlined unicellular cyanobacterium called Candidatus Atelocyanobacterium thalassa (or UCYN-A) living in a symbiosis with a phototrophic microalga. We used metabolic modeling to glean insights into UCYN-A's unique physiology and metabolic processes governing the symbiotic association. To this end, we developed an optimization-based framework that infers all possible trophic scenarios consistent with the observed data. Possible mechanisms employed by UCYN-A to accommodate diazotrophy with daytime carbon fixation by the host (i.e., two mutually incompatible processes) were also elucidated. We found that the metabolic functions of the two constituents, and UCYN-A's streamlined genome is optimized to support maximal nitrogen fixation flux, alluding that this symbiosis is as close to being a functional 'nitroplast' as any observed till date. We envision that the developed framework using UCYN-A and its algal host will be used as a roadmap and motivate the study of similarly unique microbial systems in the future. Understanding how genomic mutations impact the overall phenotype of an organism has been a focus of efforts aimed at improving growth yield, determining genetic markers governing a trait, and understanding adaptive processes. This has been performed conventionally using genome-wide association studies, which seek to identify the genetic background behind a trait by examining associations between phenotypes and single-nucleotide polymorphisms (SNPs). Although such studies are common, biological interpretation of the results remains a challenge; especially due to the confounding nature of population structure and the systematic biases thus introduced. In Chapter 4, we propose a complementary tool called SNPeffect that offers putative genotype-to-phenotype mechanistic interpretations by integrating biochemical knowledge encoded in metabolic models. SNPeffect was used to explain differential growth rate and metabolite accumulation in Arabidopsis and poplar as the outcome of SNPs in enzyme-coding genes. To this end, we also constructed a genome-scale metabolic model for Populus trichocarpa, the first for a perennial woody tree. As expected, our results indicated that growth is a complex polygenic trait governed by carbon and energy partitioning. The predicted set of functional SNPs in both species are associated with experimentally-characterized growth-determining genes and also suggest putative ones. Functional SNPs were found in pathways such as amino-acid metabolism, nucleotide biosynthesis, and cellulose and lignin biosynthesis, in line with breeding strategies that target pathways governing carbon and energy partition. Thus far, we have developed computational frameworks that examine how the metabolism of an organism dictates its total phenotype and interactions with other organisms in a community. In Chapter 5, we take the next step by examining ways in which an organism can impact its host, specifically how the infant gut microbiome is shaped. Fecal samples from newborn infants showed that gut bacteria is detectable by 16 h after birth. However, analysis of the microbiome, proteome, and metabolome data did not suggest a single genomic signature for neonatal gut colonization. Using flux balance modeling, we found E. coli to be the most common early colonizer. The appearance of bacteria was associated with decreased levels of free amino acids and an increase in products of bacterial fermentation, primarily acetate and succinate. Among all the microbial species found, these observations were only consistent with E. coli growing under anaerobic conditions using amino acid fermentation to support maximal ATP yield. These results provide a deep characterization of the first microbes in the human gut and show how the biochemical environment is altered by their appearance. Finally, in Chapter 6, we conclude with our efforts to develop computational frameworks enabling the integration of heterogeneous datasets within constraints-based optimization. We discuss current challenges associated with such modeling frameworks and their uses, and finally present future perspectives for augmenting these models with the incorporation of diverse data types, multi-scale modeling, cross-cutting applications.
Author: Adil Mardinoglu
Publisher: Frontiers Media SA
ISBN: 2889451402
Category :
Languages : en
Pages : 98
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Book Description
Complex disorders including obesity, diabetes, fatty liver disease, cardiovascular disease and cancer are results from a combination of genetic, environmental and lifestyle factors. The prevalence of such disorders has increased dramatically in the last two decades and there is an urgent need for the development of new prognostic tools for the treatment of such diseases. However, this requires a deep understanding of the underlying molecular mechanisms involved in the occurrence of the diseases. With the advances in high throughput technologies, biological components of cells can be measured with a very high resolution and these data can be used for investigating whole systems properties using a network-based approach. Systems medicine provides an integrative platform for studying the interactions between the biological components of the cell using a holistic approach and generating mechanistic explanations for the emergent systems properties. This inter-disciplinary field of study allows for understanding biological processes of cells in health and disease states, gaining new insights into what drives the appearance of the disease and finally identifying proteins and metabolites implicated in human disease. Systems medicine utilizes mathematical approaches to generate models which can be employed for designing new sets of experiments and for mapping the response of the system to perturbations quantitatively. These models as well as the developed tools can accelerate the emergence of personalized medicine which can transform the practice of medicine and offer better targets for drug development with minimum side effects.
Author: J. Jost
Publisher: Birkhäuser
ISBN: 3034891180
Category : Science
Languages : en
Pages : 581
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Book Description
The occurrence of 5-methylcytosine in DNA was first described in 1948 by Hotchkiss (see first chapter). Recognition of its possible physiologi cal role in eucaryotes was first suggested in 1964 by Srinivasan and Borek (see first chapter). Since then work in a great many laboratories has established both the ubiquity of 5-methylcytosine and the catholicity of its possible regulatory function. The explosive increase in the number of publications dealing with DNA methylation attests to its importance and makes it impossible to write a comprehensive coverage of the literature within the scope of a general review. Since the publication of the 3 most recent books dealing with the subject (DNA methylation by Razin A. , Cedar H. and Riggs A. D. , 1984 Springer Verlag; Molecular Biology of DNA methylation by Adams R. L. P. and Burdon R. H. , 1985 Springer Verlag; Nucleic Acids Methylation, UCLA Symposium suppl. 128, 1989) considerable progress both in the techniques and results has been made in the field of DNA methylation. Thus we asked several authors to write chapters dealing with aspects of DNA methyla tion in which they are experts. This book should be most useful for students, teachers as well as researchers in the field of differentiation and gene regulation. We are most grateful to all our colleagues who were willing to spend much time and effort on the publication of this book. We also want to express our gratitude to Yan Chim Jost for her help in preparing this book.
Author: Gyun Min Lee
Publisher: John Wiley & Sons
ISBN: 3527343342
Category : Science
Languages : en
Pages : 436
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Book Description
Offers a comprehensive overview of cell culture engineering, providing insight into cell engineering, systems biology approaches and processing technology In Cell Culture Engineering: Recombinant Protein Production, editors Gyun Min Lee and Helene Faustrup Kildegaard assemble top class authors to present expert coverage of topics such as: cell line development for therapeutic protein production; development of a transient gene expression upstream platform; and CHO synthetic biology. They provide readers with everything they need to know about enhancing product and bioprocess attributes using genome-scale models of CHO metabolism; omics data and mammalian systems biotechnology; perfusion culture; and much more. This all-new, up-to-date reference covers all of the important aspects of cell culture engineering, including cell engineering, system biology approaches, and processing technology. It describes the challenges in cell line development and cell engineering, e.g. via gene editing tools like CRISPR/Cas9 and with the aim to engineer glycosylation patterns. Furthermore, it gives an overview about synthetic biology approaches applied to cell culture engineering and elaborates the use of CHO cells as common cell line for protein production. In addition, the book discusses the most important aspects of production processes, including cell culture media, batch, fed-batch, and perfusion processes as well as process analytical technology, quality by design, and scale down models. -Covers key elements of cell culture engineering applied to the production of recombinant proteins for therapeutic use -Focuses on mammalian and animal cells to help highlight synthetic and systems biology approaches to cell culture engineering, exemplified by the widely used CHO cell line -Part of the renowned "Advanced Biotechnology" book series Cell Culture Engineering: Recombinant Protein Production will appeal to biotechnologists, bioengineers, life scientists, chemical engineers, and PhD students in the life sciences.
Author: Jyoti Sharma
Publisher: Frontiers Media SA
ISBN: 2889661253
Category : Science
Languages : en
Pages : 154
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Book Description
This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.
Author: Manish Kumar Gupta
Publisher: Elsevier
ISBN: 0443160937
Category : Science
Languages : en
Pages : 434
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Book Description
Integrative Omics: Concepts, Methodology and Applications provides a holistic and integrated view of defining and applying network approaches, integrative tools, and methods to solve problems for the rationalization of genotype to phenotype relationships. The reference includes a range of chapters in a systemic ‘step by step’ manner, which begins with the basic concepts from Omic to Multi Integrative Omics approaches, followed by their full range of approaches, applications, emerging trends, and future trends. All key areas of Omics are covered including biological databases, sequence alignment, pharmacogenomics, nutrigenomics and microbial omics, integrated omics for Food Science and Identification of genes associated with disease, clinical data integration and data warehousing, translational omics as well as omics technology policy and society research. Integrative Omics: Concepts, Methodology and Applications highlights the recent concepts, methodologies, advancements in technologies and is also well-suited for researchers from both academic and industry background, undergraduate and graduate students who are mainly working in the area of computational systems biology, integrative omics and translational science. The book bridges the gap between biological sciences, physical sciences, computer science, statistics, data science, information technology and mathematics by presenting content specifically dedicated to mathematical models of biological systems. Provides a holistic, integrated view of a defining and applying network approach, integrative tools, and methods to solve problems for rationalization of genotype to phenotype relationships Offers an interdisciplinary approach to Databases, data analytics techniques, biological tools, network construction, analysis, modeling, prediction and simulation of biological systems leading to ‘translational research’, i.e., drug discovery, drug target prediction, and precision medicine Covers worldwide methods, concepts, databases, and tools used in the construction of integrated pathways
Author: Fumiaki Uchiumi
Publisher: Elsevier
ISBN: 0128194618
Category : Science
Languages : en
Pages : 236
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Book Description
Recent studies in human genetics and in silico analyses have revealed that a number of genes are head-head orientated with other genes or non-coding RNAs. The expression of regulatory element-containing 5’-upstream regions of gene pairs are referred to as bi-directional promoters and are thought to have a key role in biological regulatory mechanisms. For example, tumor suppressor protein-encoding TP53 and BRCA1 genes are head-head bound with WRAP53 and NBR2, respectively. DNA-repair factor-encoding ATM and PRKDC (DNA-PKcs) genes have bidirectional partner NPAT and MCM4, respectively. Surveillance of the human DNA database has revealed that the numbers of DNA repair/mitochondrial function/immune response-associated genes are bound with other genes that are transcribed to opposite direction. The observations may encourage us to investigate in the molecular mechanisms how DNA repair/mitochondrial function/immune response-associated genes are regulated by bidirectional promoters. Not only protein-coding genes, but also quite a few ncRNAs, which play important roles in various cellular events, are transcribed under the regulation of the bidirectional promoters. More importantly, we know that dysregulation in the promoter activity and transcription initiation of genes might cause human diseases. Provides an overview of the process of transcription Explains why there so many bidirectional promoters present in human genomes Covers how the diverse biological functions of (non-coding RNAs) ncRNAs are controlled
Author: George Tseng
Publisher: Cambridge University Press
ISBN: 1107069114
Category : Mathematics
Languages : en
Pages : 497
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Book Description
Tutorial chapters by leaders in the field introduce state-of-the-art methods to handle information integration problems of omics data.
