
Biomedical Informatics in Translational Research
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Content
- Biomedical Informatics in Translational Research
- Contents
- Preface
- Chapter 1 Biomedical Informatics in TranslationalResearch
- 1.1 Evolution of Terminology
- 1.1.1 Translational Research
- 1.1.2 Systems Biology
- 1.1.3 Personalized Medicine
- References
- Chapter 2 The Clinical Perspective
- 2.1 Introduction
- 2.2 Ethics in Clinical Research
- 2.3 Regulatory Policies for Protecting a Research Subject's Privacy
- 2.4 Informed Consent
- 2.5 Collecting Clinical Data: Developing and Administering Survey Instruments
- 2.6 Issues Important to Biomedical Informatics
- 2.6.1 Data Tracking and Centralization
- 2.6.2 Deidentifying Data
- 2.6.3 Quality Assurance
- 2.6.4 Data Transfer from the Health Care Clinic to the Research Setting
- 2.7 Standard Operating Procedures
- 2.8 Developing and Implementing a Research Protocol
- 2.8.1 Developing a Research Protocol
- 2.8.2 Implementing the Research Protocol
- 2.9 Summary
- References
- Chapter 3 Tissue Banking: Collection, Processing, and Pathologic Characterization of Biospecimens for Research
- 3.1 Introduction
- 3.1.1 A Biorepository's Mandate
- 3.1.2 Overview of Current Tissue Banking Practices
- 3.2 Consenting and Clinical Data Acquisition
- 3.3 Blood Collection, Processing, and Storage
- 3.4 Tissue Collection, Processing, Archiving, and Annotation
- 3.4.1 Tissue Collection
- 3.4.2 Tissue Processing
- 3.4.3 Tissue Archiving and Storage
- 3.4.4 Pathologic Characterization of Tissue Samples
- 3.5 Conclusion
- References
- Chapter 4 Biological Perspective
- 4.1 Background for "Omics" Technologies
- 4.2 Basic Biology and Definitions
- 4.2.1 A Historical Perspective
- 4.2.2 Biological Processes
- 4.2.3 Some Definitions
- 4.3 Very Basic Biochemistry
- 4.3.1 DNA
- 4.3.2 RNA
- 4.3.3 Proteins
- 4.4 Summary
- References
- Chapter 5 Genomics Studies
- 5.1 Introduction
- 5.2 Genomic Technologies Used for DNA Analysis
- 5.2.1 DNA Sequencing
- 5.2.1.2 Biomedical Informatics Requirements
- 5.2.1.3 Future Directions
- 5.2.2 Genotyping
- 5.2.2.1 Array Technologies
- 5.2.2.2 Technological Assessment of Genotyping
- 5.2.2.3 Affymetrix Genotyping SNP Assay Workflow
- 5.2.2.4 QA/SOP Issues
- 5.2.2.5 Biomedical Informatics Requirements
- 5.2.2.6 Future Directions
- 5.2.3 Array-Based Comparative Genomic Hybridization
- 5.2.3.1 Technological Assessment of Chromosomal Rearrangements
- 5.2.3.2 Example Platform
- 5.2.3.3 QA/SOP Issues
- 5.2.3.4 Biomedical Informatics Requirements
- 5.2.3.5 Oligo-Based aCGH Platform
- 5.3 Genomic Technology Used for RNA Analysis
- 5.3.1 Real-Time PCR
- 5.3.1.1 Data Analysis Methods
- 5.3.1.2 Biomedical Informatics Requirements
- 5.3.1.3 Future Directions
- 5.3.2 Microarrays
- 5.3.2.1 Array Technologies
- 5.3.2.2 Example Platform
- 5.3.2.3 QA/SOP Issues
- 5.3.2.4 MIAME Checklist and Platform Comparison
- 5.3.2.5 Data Analysis Issues
- 5.3.2.6 Biomedical Informatics Requirements
- 5.3.2.7 Future Directions
- 5.3.3 Chips for Alternative Splicing Analysis (GeneChip Exon)
- 5.3.3.1 Array Technology
- 5.3.3.2 Biomedical Informatics Requirements
- 5.3.3.3 Future Directions
- 5.4 Translational Research Case Studies
- 5.4.1 Case 1
- 5.4.2 Case 2
- 5.5 Summary
- References
- Chapter 6 Proteomics
- 6.1 Introduction
- 6.2 Clinical Specimens
- 6.2.1 Body Fluids
- 6.2.2 Tissue
- 6.2.1.1 Blood
- 6.2.1.2 Urine
- 6.2.1.3 Cerebrospinal Fluid
- 6.3 Proteomics Technologies
- 6.3.1 Two-Dimensional Gel Electrophoresis
- 6.3.2 MALDI-TOF
- 6.3.3 Liquid Chromatography Mass Spectrometry
- 6.3.3.1 Shotgun Proteomics
- 6.3.3.2 Characterization of Posttranslational Modification of Proteins Using the Shotgun Approach
- 6.3.4 Protein Arrays
- 6.4 Analysis of Proteomics Data
- 6.4.1 2D DIGE Data Analysis
- 6.4.2 SELDI-TOF/MALDI-TOF Data Analysis
- 6.4.3 Shotgun Proteomics Data Analysis
- 6.5 Summary
- References
- Chapter 7 Data Tracking Systems
- 7.1 Introduction
- 7.1.1 Definition of a Data Tracking System
- 7.1.2 Why Use a Data Tracking System?
- 7.2 Overview of Data Tracking Systems
- 7.2.1 Historical Review
- 7.2.2 Available Resources
- 7.2.3 Data Tracking Systems in the Life Sciences
- 7.2.3.1 Clinical Data Collection
- 7.2.3.2 Tissue Processing and Banking
- 7.2.3.3 Data Tracking for Genomics and Proteomics Studies
- 7.3 Major Requirements of a Data Tracking System for Biomedical Informatics Research
- 7.3.1 General Requirements
- 7.3.2 Front-End Requirements
- 7.3.3 Back-End Requirements
- 7.3.4 Field-Specific Requirements
- 7.3.4.1 Requirements for Clinical Data Tracking
- 7.3.4.2 Requirements for Tissue Banking and Specimen Preparation
- 7.3.4.3 Requirements for Genomics Experiments
- 7.3.4.4 Requirements for Proteomics Experiments
- 7.3.5 Additional Points
- 7.4 Ways to Establish a Data Tracking System
- 7.4.1 Buy a System Off the Shelf
- 7.4.2 Develop a System
- 7.4.3 Pursue a Hybrid Approach
- 7.5 Deployment Challenges and Other Notes
- 7.5.1 Resistance from End Users
- 7.5.2 Training
- 7.5.3 Mismatches Between System Features and Real Needs
- 7.5.4 Protocol Changes and Other Evolutions
- 7.5.5 Data Tracking System as a Data Source
- 7.6 Summary
- References
- Chapter 8 Data Centralization
- 8.1 An Overview of Data Centralization
- 8.2 Types of Data in Question
- 8.2.1 in-house Patient-Centric Clinical, Genomic, and Proteomic Data
- 8.2.2 Publicly Available Annotation and Experimental Data
- 8.2.2.1 Popular Public Databases
- 8.2.2.2 Public Databases of Special Values
- 8.2.2.3 Considerations and Concerns About Using or Integrating Public Data
- 8.2.3 Data Format Standards
- 8.3 DW Development for Integrative Biomedical Informatics Research
- 8.3.1 Selection of the Developing Partner-Experiences in the Field
- 8.3.2 DW Requirements
- 8.3.3 Data Source Selection
- 8.3.4 Hardware and the Database Management Systems Selection
- 8.3.5 DW Structural Models-Integrated, Federated, or Hybrid
- 8.3.6 Data Models: Dimensional Models, Data Marts, and Normalization Levels
- 8.3.7 Data Models: EAV, Entity-Relationship, and Object-Oriented Modules
- 8.3.8 Data Models: Handling of the Temporal Information
- 8.3.9 Data Extraction, Cleansing, Transformation, and Loading
- 8.3.10 Tuning and QA
- 8.3.11 Changes-The Dynamic Nature
- 8.4 Use of the DW
- 8.5 Example Case
- 8.6 Summary
- References
- Chapter 9 Data Analysis
- 9.1 The Nature and Diversity of Research Data in Translational Medicine
- 9.1.1 Where Data Reside
- 9.1.2 Operational Versus Analytical Data Systems
- 9.1.3 Data Warehouses
- 9.1.4 Data Preprocessing
- 9.1.4.1 Missing Value Handling
- 9.1.4.2 Outlier Removal (Clipping)
- 9.1.4.3 Binning
- 9.1.4.4 Normalization
- 9.2 Data Analysis Methods and Techniques
- 9.2.3 Predictive Modeling
- 9.2.3.1 Feature Selection
- 9.2.3.2 Regression
- 9.2.3.3 Classification
- 9.2.4 Clustering
- 9.2.4.1 Self-Organizing Maps
- 9.2.4.2 K-Means
- 9.2.4.3 Hierarchical
- 9.2.5 Evaluation and Validation Methodologies
- 9.2.5.1 Type I and Type II Errors
- 9.2.5.2 Sensitivity Versus Specificity
- 9.2.5.3 ROC Graph
- 9.2.5.4 Cross Validation
- 9.2.1 Generalized Forms of Analysis
- 9.2.1.1 Significance Testing
- 9.2.1.2 Predictive Modeling
- 9.2.1.3 Clustering
- 9.2.2 Significance Testing
- 9.2.2.1 Pearson's Chi-Square Test
- 9.2.2.2 Student's t-Test
- 9.2.2.3 ANOVA
- 9.2.2.4 Wilcoxon Signed-Rank Test
- 9.3 Analysis of High-Throughput Genomic and Proteomic Data
- 9.3.1 Genomic Data
- 9.3.1.1 Different Platforms Available
- 9.3.1.2 Quality Control
- 9.3.1.3 Image Analysis
- 9.3.1.4 Data Normalization and Transformation
- 9.3.1.5 Statistical Analysis
- 9.3.1.6 High-Level Analysis: Profiling or Pattern Recognition
- 9.3.2 Proteomic Data
- 9.3.3 Functional Determination
- 9.3.3.1 Gene Ontology
- 9.3.3.2 Pathway Analysis
- 9.4 Analysis of Clinical Data
- 9.5 Analysis of Textual Data
- 9.5.1 Data Sources
- 9.5.2 Biological Entity
- 9.5.3 Mining Relations Between Named Entities
- 9.6 Integrative Analysis and Application Examples
- 9.7 Data Analysis Tools and Resources
- 9.8 Summary
- References
- Chapter 10 Research and Application: Examples
- 10.1 Introduction
- 10.2 deCODE Genetics
- 10.2.1 Data Repository Development and Data Centralization
- 10.2.1.1 Clinical Data Collection: Patient Consent and Deidentification
- 10.2.2 Genomic Studies
- 10.2.2.1 Linkage Analysis
- 10.2.2.2 Association Studies
- 10.2.2.3 Limitations
- 10.2.2.4 Analysis Tool
- 10.2.3 Application
- 10.2.3.1 Drug Development Based on Identification of Genotype for Myocardial Infarction Risk
- 10.2.3.2 Development of a Diagnostic to Detect a Diabetes Risk Genotype
- 10.3 Windber Research Institute
- 10.3.1 Clinical Data Collection and Storage
- 10.3.1.1 The Clinical Breast Care Project
- 10.3.1.2 Integrative Cardiac and Metabolic Health Program
- 10.3.2 Data Tracking
- 10.3.3 Data Centralization
- 10.3.4 Genomic and Proteomic Studies
- 10.3.4.1 Allelic Imbalance to Characterize Genomic Instability
- 10.3.4.2 Proteomic Analysis of Cardiovascular Risk Factor Modification
- 10.3.5 Data Analysis, Data Mining, and Data Visualization
- 10.3.5.1 Knowledge Development Environment
- 10.3.5.2 Pathology Co-Occurrence Analysis
- 10.3.6 Outcomes Summary
- 10.4 Conclusions
- References
- Chapter 11 Clinical Examples: A Biomedical Informatics Approach
- 11.1 Understanding the Role of Biomarkers and Diagnostics
- 11.2 Understanding the Difference Between Pathways and Networks
- 11.3 How Biomarkers/Diagnostics and Pathways/Networks Are Linked
- 11.4 Breast Cancer
- 11.5 Menopause
- 11.6 Coagulation/DIC
- 11.7 Conclusions
- References
- About the Editors
- About the Contributors
- Index
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