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Nucleic Acids as Molecular Diagnostics


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Preface NEXT-GENERATION SEQUENCING FOR CLINICAL DIAGNOSTICS OF CARDIOMYOPATHIES Introduction Cardiomyopathies and Why Genetic Testing is Needed NGS NGS for Cardiomyopathies Sample Preparation Bioinformatics Analysis Pipeline Interpretation of Results and Translation into Clinical Practice MICRORNAs AS NOVEL BIOMARKERS IN CARDIOVASCULAR MEDICINE Introduction miRNAs are Associated with Cardiovascular Risk Factors miRNAs in Coronary Artery Disease miRNAs in Cardiac Ischemia and Necrosis miRNAs as Biomarkers of Heart Failure Future Challenges MICRORNAs IN PRIMARY BRAIN TUMORS: FUNCTIONAL IMPACT AND POTENTIAL USE FOR DIAGNOSTIC PURPOSES Background Gliomas Meningiomas Pituitary Adenomas Medulloblastomas Other Brain Tumors Summary and Outlook GENETIC AND EPIGENETIC ALTERATIONS IN SPORADIC COLORECTAL CANCER: CLINICAL IMPLICATIONS Introduction Microsatellite Instability Driver Somatic Mutations in CRC Epigenetic Instability in CRC Hypomethylation CpG Island Methylator Phenotype Concluding Remarks NUCLEIC ACID-BASED MARKERS IN UROLOGIC MALIGNANCIES Introduction Bladder Cancer Prostate Cancer Renal Cell Carcinoma Summary FROM THE GENETIC MAKE-UP TO THE MOLECULAR SIGNATURE OF NON-CODING RNA IN BREAST CANCER Introduction Molecular Breast Cancer Detection Molecular Breast Cancer Subtypes and Prognostic/Predictive Molecular Biomarkers NUCLEIC ACID-BASED DIAGNOSTICS IN GYNECOLOGICAL MALIGNANCIES Introduction Cervix, Vulva, and Vaginal Carcinoma Endometrial Carcinoma (Carcinoma Corpus Uteri) Ovarian Carcinoma Breast Cancer Conclusion NUCLEIC ACIDS AS MOLECULAR DIAGNOSTICS IN HEMATOPOIETIC MALIGNANCIES - IMPLICATIONS IN DIAGNOSIS, PROGNOSIS, AND THERAPEUTIC MANAGEMENT Introduction Methodological Approaches Cytogenetic Analysis to Molecular Diagnostics Minimal Residual Disease Chronic Myeloid Leukemia Acute Myeloid Leukemia Acute Lymphocytic Leukemia Chronic Lymphocytic Leukemia Outlook and Perspectives TECHNIQUES OF NUCLEIC ACID-BASED DIAGNOSIS IN THE MANAGEMENT OF BACTERIAL AND VIRAL INFECTIOUS DISEASES Importance of Nucleic Acid-Based Molecular Assays in Clinical Microbiology Nucleic Acid Amplification Techniques Post-Amplification Analyses General Overview and Concluding Remarks MICRORNAs IN HUMAN MICROBIAL INFECTIONS AND DISEASE OUTCOMES Introduction General Aspects of miRNAs in Infectious Diseases miRNAs as Biomarkers and Therapeutic Agents in Tuberculosis and Hepatitis C Infections miRNA-Targeting Therapeutics Concluding Remarks TOWARDS THE IDENTIFICATION OF CONDITION-SPECIFIC MICROBIAL POPULATIONS FROM HUMAN METAGENOMIC DATA Introduction Nucleic Acid-Based Methods in Diagnostic Microbiology Need for Comprehensive Microbiome Characterization in Medical Diagnostics Challenges for Metagenomics-Based Diagnostics: Read Lengths, Sequencing Library Sizes, and Microbial Community Composition Deconvolution of Population-Level Genomic Complements from Metagenomic Data Need for Comparative Metagenomic Data Analysis Tools Future Perspectives in Microbiome-Enabled Diagnostics GENOME, EXOME, AND GENE PANEL SEQUENCING IN A CLINICAL SETTING Introduction Genetic Diagnostics from a Laboratory Perspective - From Sanger to NGS NGS Diagnostics in a Clinical Setting - Comparison Between Genome, Exome, and Panel Diagnostics Conclusion and Outlook ANALYSIS OF NUCLEIC ACIDS IN SINGLE CELLS Introduction Isolating Single Cells Looking at the DNA of a Single Cancer Cell Molecular DNA Analysis in Single Cells Approaches to Analyze RNA of a Single Cell Expression Analysis in Single Cells and its Biological Relevance in Cancer Thoughts on Bioinformatics Approaches Future Impact of Single-Cell Analysis in Clinical Diagnosis DETECTING DYSREGULATED PROCESSES AND PATHWAYS Introduction Measuring and Normalizing Expression Profiles Biological Networks Measuring the Degree of Deregulation of Individual Genes Over-Representation Analysis and Gene Set Enrichment Analysis Detecting Deregulated Networks and Pathways miRNA Expression Data Differential Network Analysis Conclusion COMPANION DIAGNOSTICS AND BEYOND - AN ESSENTIAL ELEMENT IN THE PUZZLE OF TRANSFORMING HEALTHCARE Introduction The Healthcare Environment What is Companion Diagnostics? What are the Drivers for Companion Diagnostics? Companion Diagnostics Market Partnerships and Business Models for Companion Diagnostics Regulatory Environment for Compantion Diagnostics Tests Outlook - Beyond Companion Diagnostics Towards Holistic Solutions ETHICAL, LEGAL, AND PSYCHOSOCIAL ASPECTS OF MOLECULAR GENETIC DIAGNOSIS General Peculiarities of Genetic Diagnoses Informed Consent and Genetic Counseling Medical Secrecy and Data Protection Predictive Diagnosis Prenatal Diagnosis Multiparameter Testing Index

About the Author

Andreas Keller studied Computational Biology at Saarland University in Saarbrucken (Germany), completing his PhD in 2009. He joined Febit Biomed GmbH in 2008 where he directed the biomarker discovery effort. In 2011, he joined the healthcare division of Siemens AG in Erlangen as director diagnostic innovation. In 2013 he became professor for Clinical Computational Biology at Saarland University. Dr. Keller has published more than 80 peer-reviewed manuscripts and field more than 30 patents in the area of biomarker discovery and molecular diagnostics. Eckart Meese is Professor of Human Genetics and Molecular Biology at Saarland University Medical School in Homburg (Germany), where he directs the Institute of Human Genetics. He obtained his PhD in biology in 1987 and did postdoc work at the Arizona Cancer Center in Tucson (USA). He then joined the University of Michigan Medical Center as Assistant Professor, before joining Saarland University in 1992. His scientific focus is on miRNA and autoantibody profiling for the diagnosis of cancer and other diseases.

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