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Technology and Method Developments for High-throughput Translational Medicine

Technology and Method Developments for High-throughput Translational Medicine PDF Author: Junhee Seok
Publisher: Stanford University
ISBN:
Category :
Languages : en
Pages : 122

Book Description
Translation of knowledge from basic science to medicine is essential to improving both clinical research and practice. In this translation, high-throughput genomic approaches can greatly accelerate our understanding of molecular mechanisms of diseases. A successful high-throughput genomic study of disease requires, first, comprehensive and efficient platforms to collect genomic data from clinical samples, and second, computational analysis methods that utilize databases of prior biological knowledge together with experimental data to derive clinically meaningful results. In this thesis, we discuss the development of a new microarray platform as well as computational methods for knowledge-based analysis along with their applications in clinical research. First, we and other colleagues have developed a new high-density oligonucleo-tide array of the human transcriptome for high-throughput and cost-efficient analysis of patient samples in clinical studies. This array allows comprehensive examination of gene expression and genome-wide identification of alternative splicing, and also pro-vides assays for coding SNP detection and non-coding transcripts. Compared with high-throughput mRNA sequencing technology, we show that this array is highly re-producible in estimating gene and exon expression, and sensitive in detecting expres-sion changes. In addition, the exon-exon junction feature of this array is shown to im-prove detection efficiency for mRNA alternative splicing when combined with an ap-propriate computational method. We implemented the use of this array in a multi-center clinical program and have obtained comparable levels of high quality and re-producible data. With low costs and high throughputs for sample processing, we antic-ipate that this array platform will have a wide range of applications in high-throughput clinical studies. Second, we investigated knowledge-based methods that utilize prior know-ledge from biology and medicine to improve analysis and interpretation of high-throughput genomic data. We have developed knowledge-based methods to enrich our prior knowledge, illustrate dynamic response to external stimulus, and identify distur-bances in cellular pathways by chemical exposure, as well as discover hidden biological signatures for the prediction of patient outcomes. Finally, we applied a knowledge-based approach in a large scale genomic study of trauma patients. Cooperating with clinical information, prior knowledge improved the interpretation of common and dif-ferential genomic response to injury, and provided efficient risk assessment for patient outcomes. The clinical and genomic data as well as analysis results in this trauma study were systematically organized and provided to research communities as new knowledge of traumatic injury. The microarray platform and knowledge-based methods presented in this thesis provide appropriate research tools for high-throughput translational medicine in a large clinical setting. This thesis is expected to advance understanding and treatment for dis-eases, and finally, improve public health.

Technology and Method Developments for High-throughput Translational Medicine

Technology and Method Developments for High-throughput Translational Medicine PDF Author: Junhee Seok
Publisher: Stanford University
ISBN:
Category :
Languages : en
Pages : 122

Book Description
Translation of knowledge from basic science to medicine is essential to improving both clinical research and practice. In this translation, high-throughput genomic approaches can greatly accelerate our understanding of molecular mechanisms of diseases. A successful high-throughput genomic study of disease requires, first, comprehensive and efficient platforms to collect genomic data from clinical samples, and second, computational analysis methods that utilize databases of prior biological knowledge together with experimental data to derive clinically meaningful results. In this thesis, we discuss the development of a new microarray platform as well as computational methods for knowledge-based analysis along with their applications in clinical research. First, we and other colleagues have developed a new high-density oligonucleo-tide array of the human transcriptome for high-throughput and cost-efficient analysis of patient samples in clinical studies. This array allows comprehensive examination of gene expression and genome-wide identification of alternative splicing, and also pro-vides assays for coding SNP detection and non-coding transcripts. Compared with high-throughput mRNA sequencing technology, we show that this array is highly re-producible in estimating gene and exon expression, and sensitive in detecting expres-sion changes. In addition, the exon-exon junction feature of this array is shown to im-prove detection efficiency for mRNA alternative splicing when combined with an ap-propriate computational method. We implemented the use of this array in a multi-center clinical program and have obtained comparable levels of high quality and re-producible data. With low costs and high throughputs for sample processing, we antic-ipate that this array platform will have a wide range of applications in high-throughput clinical studies. Second, we investigated knowledge-based methods that utilize prior know-ledge from biology and medicine to improve analysis and interpretation of high-throughput genomic data. We have developed knowledge-based methods to enrich our prior knowledge, illustrate dynamic response to external stimulus, and identify distur-bances in cellular pathways by chemical exposure, as well as discover hidden biological signatures for the prediction of patient outcomes. Finally, we applied a knowledge-based approach in a large scale genomic study of trauma patients. Cooperating with clinical information, prior knowledge improved the interpretation of common and dif-ferential genomic response to injury, and provided efficient risk assessment for patient outcomes. The clinical and genomic data as well as analysis results in this trauma study were systematically organized and provided to research communities as new knowledge of traumatic injury. The microarray platform and knowledge-based methods presented in this thesis provide appropriate research tools for high-throughput translational medicine in a large clinical setting. This thesis is expected to advance understanding and treatment for dis-eases, and finally, improve public health.

Technology and Method Developments for High-throughput Translational Medicine

Technology and Method Developments for High-throughput Translational Medicine PDF Author: Junhee Seok
Publisher:
ISBN:
Category :
Languages : en
Pages :

Book Description


Improving and Accelerating Therapeutic Development for Nervous System Disorders

Improving and Accelerating Therapeutic Development for Nervous System Disorders PDF Author: Institute of Medicine
Publisher: National Academies Press
ISBN: 0309292492
Category : Medical
Languages : en
Pages : 107

Book Description
Improving and Accelerating Therapeutic Development for Nervous System Disorders is the summary of a workshop convened by the IOM Forum on Neuroscience and Nervous System Disorders to examine opportunities to accelerate early phases of drug development for nervous system drug discovery. Workshop participants discussed challenges in neuroscience research for enabling faster entry of potential treatments into first-in-human trials, explored how new and emerging tools and technologies may improve the efficiency of research, and considered mechanisms to facilitate a more effective and efficient development pipeline. There are several challenges to the current drug development pipeline for nervous system disorders. The fundamental etiology and pathophysiology of many nervous system disorders are unknown and the brain is inaccessible to study, making it difficult to develop accurate models. Patient heterogeneity is high, disease pathology can occur years to decades before becoming clinically apparent, and diagnostic and treatment biomarkers are lacking. In addition, the lack of validated targets, limitations related to the predictive validity of animal models - the extent to which the model predicts clinical efficacy - and regulatory barriers can also impede translation and drug development for nervous system disorders. Improving and Accelerating Therapeutic Development for Nervous System Disorders identifies avenues for moving directly from cellular models to human trials, minimizing the need for animal models to test efficacy, and discusses the potential benefits and risks of such an approach. This report is a timely discussion of opportunities to improve early drug development with a focus toward preclinical trials.

Basic Principles of Drug Discovery and Development

Basic Principles of Drug Discovery and Development PDF Author: Benjamin E. Blass
Publisher: Academic Press
ISBN: 0128172150
Category : Medical
Languages : en
Pages : 712

Book Description
Basic Principles of Drug Discovery and Development presents the multifaceted process of identifying a new drug in the modern era, which requires a multidisciplinary team approach with input from medicinal chemists, biologists, pharmacologists, drug metabolism experts, toxicologists, clinicians, and a host of experts from numerous additional fields. Enabling technologies such as high throughput screening, structure-based drug design, molecular modeling, pharmaceutical profiling, and translational medicine are critical to the successful development of marketable therapeutics. Given the wide range of disciplines and techniques that are required for cutting edge drug discovery and development, a scientist must master their own fields as well as have a fundamental understanding of their collaborator’s fields. This book bridges the knowledge gaps that invariably lead to communication issues in a new scientist’s early career, providing a fundamental understanding of the various techniques and disciplines required for the multifaceted endeavor of drug research and development. It provides students, new industrial scientists, and academics with a basic understanding of the drug discovery and development process. The fully updated text provides an excellent overview of the process and includes chapters on important drug targets by class, in vitro screening methods, medicinal chemistry strategies in drug design, principles of in vivo pharmacokinetics and pharmacodynamics, animal models of disease states, clinical trial basics, and selected business aspects of the drug discovery process. Provides a clear explanation of how the pharmaceutical industry works, as well as the complete drug discovery and development process, from obtaining a lead, to testing the bioactivity, to producing the drug, and protecting the intellectual property Includes a new chapter on the discovery and development of biologics (antibodies proteins, antibody/receptor complexes, antibody drug conjugates), a growing and important area of the pharmaceutical industry landscape Features a new section on formulations, including a discussion of IV formulations suitable for human clinical trials, as well as the application of nanotechnology and the use of transdermal patch technology for drug delivery Updated chapter with new case studies includes additional modern examples of drug discovery through high through-put screening, fragment-based drug design, and computational chemistry

Evolution of Translational Omics

Evolution of Translational Omics PDF Author: Institute of Medicine
Publisher: National Academies Press
ISBN: 0309224187
Category : Science
Languages : en
Pages : 354

Book Description
Technologies collectively called omics enable simultaneous measurement of an enormous number of biomolecules; for example, genomics investigates thousands of DNA sequences, and proteomics examines large numbers of proteins. Scientists are using these technologies to develop innovative tests to detect disease and to predict a patient's likelihood of responding to specific drugs. Following a recent case involving premature use of omics-based tests in cancer clinical trials at Duke University, the NCI requested that the IOM establish a committee to recommend ways to strengthen omics-based test development and evaluation. This report identifies best practices to enhance development, evaluation, and translation of omics-based tests while simultaneously reinforcing steps to ensure that these tests are appropriately assessed for scientific validity before they are used to guide patient treatment in clinical trials.

Chemical Genomics

Chemical Genomics PDF Author: Haian Fu
Publisher: Cambridge University Press
ISBN: 1107377587
Category : Science
Languages : en
Pages : 359

Book Description
Advances in chemistry, biology and genomics coupled with laboratory automation and computational technologies have led to the rapid emergence of the multidisciplinary field of chemical genomics. This edited text, with contributions from experts in the field, discusses the new techniques and applications that help further the study of chemical genomics. The beginning chapters provide an overview of the basic principles of chemical biology and chemical genomics. This is followed by a technical section that describes the sources of small-molecule chemicals; the basics of high-throughput screening technologies; and various bioassays for biochemical-, cellular- and organism-based screens. The final chapters connect the chemical genomics field with personalized medicine and the druggable genome for future discovery of new therapeutics. This book will be valuable to researchers, professionals and graduate students in many fields, including biology, biomedicine and chemistry.

Encyclopedia of Creativity, Invention, Innovation and Entrepreneurship

Encyclopedia of Creativity, Invention, Innovation and Entrepreneurship PDF Author:
Publisher: Springer
ISBN: 9783319153469
Category : Business & Economics
Languages : en
Pages : 2500

Book Description
The second edition of this exhaustive work (ECIIE) comprehensively covers the broad spectrum of topics relating to the process of creativity and innovation, from a wide variety of perspectives (e.g., economics, management, psychology, anthropology, policy, technology, education, the arts) and modes (individual, organization, industry, nation, region). This edition includes some 400 topical entries, definitions of key terms and concepts and review essays, from a global array of more than 250 researchers, business executives, policymakers, and artists, illuminating the many facets of creativity and innovation and highlighting their relationships to such universal concepts as knowledge management, economic opportunity, and sustainability. Entries feature description of key concepts and definition of terms, full-color illustrations, case examples, future directions for research and application, synonyms and cross-references and bibliographic references.

Neuroscience Trials of the Future

Neuroscience Trials of the Future PDF Author: National Academies of Sciences, Engineering, and Medicine
Publisher: National Academies Press
ISBN: 0309442583
Category : Medical
Languages : en
Pages : 111

Book Description
On March 3-4, 2016, the National Academies of Sciences, Engineering, and Medicine's Forum on Neuroscience and Nervous System Disorders held a workshop in Washington, DC, bringing together key stakeholders to discuss opportunities for improving the integrity, efficiency, and validity of clinical trials for nervous system disorders. Participants in the workshop represented a range of diverse perspectives, including individuals not normally associated with traditional clinical trials. The purpose of this workshop was to generate discussion about not only what is feasible now, but what may be possible with the implementation of cutting-edge technologies in the future.

Automated Machine Learning

Automated Machine Learning PDF Author: Frank Hutter
Publisher: Springer
ISBN: 3030053180
Category : Computers
Languages : en
Pages : 223

Book Description
This open access book presents the first comprehensive overview of general methods in Automated Machine Learning (AutoML), collects descriptions of existing systems based on these methods, and discusses the first series of international challenges of AutoML systems. The recent success of commercial ML applications and the rapid growth of the field has created a high demand for off-the-shelf ML methods that can be used easily and without expert knowledge. However, many of the recent machine learning successes crucially rely on human experts, who manually select appropriate ML architectures (deep learning architectures or more traditional ML workflows) and their hyperparameters. To overcome this problem, the field of AutoML targets a progressive automation of machine learning, based on principles from optimization and machine learning itself. This book serves as a point of entry into this quickly-developing field for researchers and advanced students alike, as well as providing a reference for practitioners aiming to use AutoML in their work.

Modern Methods of Clinical Investigation

Modern Methods of Clinical Investigation PDF Author: Institute of Medicine
Publisher: National Academies Press
ISBN: 0309042860
Category : Medical
Languages : en
Pages : 241

Book Description
The very rapid pace of advances in biomedical research promises us a wide range of new drugs, medical devices, and clinical procedures. The extent to which these discoveries will benefit the public, however, depends in large part on the methods we choose for developing and testing them. Modern Methods of Clinical Investigation focuses on strategies for clinical evaluation and their role in uncovering the actual benefits and risks of medical innovation. Essays explore differences in our current systems for evaluating drugs, medical devices, and clinical procedures; health insurance databases as a tool for assessing treatment outcomes; the role of the medical profession, the Food and Drug Administration, and industry in stimulating the use of evaluative methods; and more. This book will be of special interest to policymakers, regulators, executives in the medical industry, clinical researchers, and physicians.