Advances in Computational Toxicology: Methodologies and Applications in Regulatory Science | Book-Club |
About Course
Description
This book explores the latest advancements in computational toxicology, focusing on methodologies such as predictive modeling, machine learning, and high-throughput screening. It highlights their applications in regulatory science, including risk assessment, chemical safety evaluation, and decision-making processes. The book serves as a valuable resource for understanding how computational tools are transforming toxicology and regulatory frameworks.
Implementation Plan for the Book Club Over Two Months
1. Book Selection
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Book: Advances in Computational Toxicology: Methodologies and Applications in Regulatory Science.
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Level: Intermediate to Advanced.
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Total Chapters: 12 (approximate).
2. Chapter Division
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The book will be divided into 8 parts (one part per week).
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Each week, members will read 1-2 chapters depending on the length and complexity.
3. Weekly Schedule
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Week 1: Chapter 1 (Introduction to Computational Toxicology) + Chapter 2 (Data Sources and Management).
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Week 2: Chapter 3 (Predictive Modeling in Toxicology) + Chapter 4 (Machine Learning Applications).
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Week 3: Chapter 5 (High-Throughput Screening Methods) + Chapter 6 (Chemical Safety Assessment).
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Week 4: Chapter 7 (Risk Assessment Frameworks) + Chapter 8 (Regulatory Decision-Making).
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Week 5: Chapter 9 (Case Studies in Computational Toxicology) + Chapter 10 (Challenges and Limitations).
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Week 6: Chapter 11 (Future Directions in Computational Toxicology) + Chapter 12 (Conclusion and Summary).
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Week 7: Review and Recap of Key Concepts.
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Week 8: Final Discussion and Evaluation.
4. Weekly Meetings
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Duration: 1-2 hours per meeting.
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Agenda:
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Discuss the assigned chapters.
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Explain complex concepts with the help of an instructor.
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Answer members’ questions.
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Open discussion on ideas presented in the chapters.
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Use interactive tools like presentations or videos to enhance understanding.
5. Interactive Activities
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Workshops: Organize practical workshops on using computational tools (e.g., predictive modeling software).
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Side Discussions: Create a Facebook or WhatsApp group for discussions outside meetings.
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Weekly Challenges: For example, writing a summary of the week’s chapters or analyzing a small dataset.
6. Final Evaluation
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At the end of the two months, conduct a final evaluation:
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Survey to assess the reading and meeting experience.
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General discussion session about the book as a whole.
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Members share their personal evaluation of the book and what they learned.
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What Will You Learn?
- Understand the fundamentals of computational toxicology and its role in regulatory science.
- Learn to apply predictive modeling and machine learning techniques for toxicity prediction.
- Gain knowledge of high-throughput screening methods and their use in chemical safety assessment.
- Explore the integration of computational tools into regulatory decision-making processes.
- Develop skills to interpret and communicate computational toxicology data effectively.
Course Content
Before You Start: Book Club Orientation
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Advances in Computational Toxicology: Methodologies and Applications in Regulatory Science
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Advances in Computational Toxicology: Methodologies and Applications in Regulatory Science
Chapter 1
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Abstract
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1 1 Computational Toxicology
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1 2 Domain of Computational Toxicology
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1 3 Need for Computational Toxicology
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1 4 Methods in Computational Toxicology
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1 5 Potential Applications of Computational Toxicology in Regulatory Science
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1 6 Conclusions
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Chapter 2
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ST Chapter 2 Background, Tasks, Modeling Methods, and Challenges for Computational Toxicology
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2 2 Tasks for Computational Toxicology
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2 2 2 Shaping Digitized Predictive Toxicology
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2 3 Modeling Methods for Computational Toxicology
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2 3 2 Physiologically Based Toxicokinetics Models
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2 3 4 Molecular Models
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2 3 5 QSAR Models
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2 4 Challenges for Computational Toxicology
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2 4 2 In the Face of Complex Living Systems
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2 4 3 The Everlasting List of Interlinked Chemicals as Mixtures
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Chapter 3
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Abstract
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3 1 Introduction
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3 2 Lessons Learnt from Successful Models
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3 3 Making Negative Predictions
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3 4 Moving to Quantitative Predictions and Weight of Evidence Approac
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3 5 Enabling Expert Review
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3 6 Modelling Complex Endpoints
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3 7 Conclusion and Future Directions
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Chapter 4
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Abstract
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4 1 Introduction
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4 2 Machine Learning Methods
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4 2 2 Latent Dirichlet Allocation
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4 2 3 Group Factor Analysis
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4 2 4 Tensor Factorization
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4 2 5 Multi tensor Factorization Multi
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4 3 Selected Case Studies
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4 3 2 Multi view Toxicogenomic Using Group Factor Analysis
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4 3 3 Structural Toxicogenomic Using Multi tensor Factorization
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4 3 4 Predictive Toxicogenomic Space PTGS
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4 4 Discussion
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4 5 Conclusion and Future Directions
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Chapter 5
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Abstract
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5 1 Introduction
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5 2 Method and Materials 5 2 1 Computers
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5 2 3 Reconstruction of the Human Protein Protein Interactome
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5 2 4 Collection of Disease Associated GenesProteins
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5 2 5 Network Proximity
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5 3 ResultsCase Studies
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5 4 Conclusion and Future Directions
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Chapter 6
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Mode of Action Guided, Molecular Modeling Based Toxicity Prediction ANovel Approac
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6 1 Introduction
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6 1 1 Highlights of Recent Progress in the Development of Alternative Testing Methods
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6 1 2 Mechanism Based Toxicity Prediction MIE and “Critical Target” Concept
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6 1 3 Limitations of Current In Vitro and In Silico Approaches
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6 1 4 Molecular Docking for Virtual Chemical Screening AGreen Toxicology Approach
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6 2 Methodology 6 2 1 Approach Overview
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6 2 2 Approach Implementation
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6 3 Results
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6 3 2 Structural Models of Biomacromolecular Targets
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6 3 4 In Vitro Toxicity Prediction Mode Libraries
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6 5 Conclusion and Future Directions
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Chapter 7
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AReview of Feature Reduction Methods for QSAR Based Toxicity Prediction Abstract
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7 1 Introduction
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7 2 Feature Selection
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7 2 1 Filter
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7 2 2 Wrapper
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7 2 2 2 Heuristic Selection Algorithms
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7 2 3 Embedded
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7 2 4 Hybrid and Ensemble Feature Selection
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7 3 1 Principal Component Analysis
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7 3 2 Autoencoder
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7 3 3 Linear Discriminant Analysis
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73 7 4 Miscellaneous 7 4 1 Feature Stability It is
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7 4 2 Validation of Feature Selection
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7 5 Summary
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Chapter 8
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AnOverview of National Toxicology Program’s Toxicogenomic Applications DrugMatrix and ToxF
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8 1 Introduction and History
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8 2 DrugMatrix Data
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8 3 DrugMatrix Database
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8 4 DrugMatrix GUI
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8 5 ToxFX
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8 6 Example Analysis of dE 71 Gene Expression Data Using DrugMatrix and ToxFX
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8 7 Accessing the DrugMatrix Database
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Chapter 9
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Chapter 9 APair Ranking PRank Method for Assessing Assay Transferability Among the Toxicogenom
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9 1 Introduction
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9 2 KeyQuestions in Toxicogenomics
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9 2 2 In Vitro Testing Systems
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9 3 Pair Ranking PRank Method
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9 4 Toxicogenomics Data and Annotation Resources 9 4 1 Open TG GATE
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9 4 2 Drug Induced Liver Injury DILI Annotation
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9 4 3 Therapeutic Categories
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9 4 5 Code Availability
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9 5 Case Studies
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9 5 2 Short Term Assays Show the Potential to Replace Long Term Assays
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9 5 3 TGx Assay Transferability Is Endpoint Dependent
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9 5 4 Concordance Among TGx Assays is Adverse Outcome Pathway AOP Specific
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9 5 5 Toward Biological Data Based Read Across
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9 6 Closing Remarks
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Chapter 10
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Abstract
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10 1 Introduction
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10 2 History of MD Simulations
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10 3 Types of MDSimulations
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10 3 3 Classical MD
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10 4 MDSimulation Software
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10 4 2 AMBER
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10 4 3 NAMD
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10 4 4 Desmond
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10 5 MDSimulation Protocol
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10 5 2 Preparation of the Protein Structure
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10 5 3 Generating Topology and Parameter Files
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10 5 4 Solvating the System
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10 5 9 Analyzing Trajectory
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10 6 Applications of MD Simulation
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10 6 2 Identification of the Ligand Binding Mode in α Fetoprotein
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10 6 3 Ligand Binding Interactions of Human α7 Nicotinic Acetylcholine Receptor
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10 6 4 Antagonist Binding Induced AR Structural Changes
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10 7 Future Perspectives
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Chapter 11
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Abstract
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11. 1
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11 2 Decision Domain
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11 2 1 Applicability
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11 2 2 Reliability
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11 2 3 Decidability
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11 3 Framework
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11 5 Conclusion
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Chapter 12
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Application of Computational Methods for the Safety Assessment of Food Ingredie
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12 1 Introduction
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12 2 Computational Approaches Currently Used in Food Ingredient Safety Assessments
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12 2 2 TK Modeling and Simulation
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12 2 2 2 Physiological TK Models
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12 2 3 Bioinformatic Approaches for Analysis of Potential Allergenicity of Proteins
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12 2 3 2 Criteria for Bioinformatic Analysis
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12 2 4 OFAS’s Food Ingredient Knowledgebase CERES In addition
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12 3 Current Challenges and Future Directions
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12 3 2 TK Modeling and Simulation
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12 3 3 Bioinformatic Approaches for Allergenicity
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12 4 Conclusions
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Chapter 13
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Predicting the Risks of Drug Induced Liver Injury in Humans Utilizing Computationa
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13 1 Introduction
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13 2 Annotation of DILI Risk for Marketed Drugs
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13 3 Predictive Models Developed at NCTR
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13 3 2 DILI Score Model 12
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13 3 3 Conventional QSAR 13
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13 3 4 Modified QSAR Models
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13 4 Conclusion
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Chapter 14
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Abstract
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14 1 Introduction
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14 2 Method and Materials
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14 2 2 In Vivo Toxicity Modeling
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14 3 ResultsCase Studies
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14 3 2 Expanding Biological Space Coverage Improves HumanToxicity Prediction
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14 3 2 Expanding Biological Space Coverage Improves HumanToxicity Prediction
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14 3 3 The Tox21 Data Challenge—New Methods for Data Modeling Thehigh
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14 4 Discussion Notes
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14 5 Conclusions and Future Directions
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Chapter 15
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Abstract
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15 1 Introduction
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15 2 Infer In Vivo PODs with Transcriptomic Data from the Same Tissues
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15 2 2 Important Issues for Inferring PODs from Transcriptomic Data
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15 3 PODsBased on In Vitro Assays
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15 5 Conclusions
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Chapter 16
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Molecular Modeling Method Applications Abstract
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16 1 Introduction
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16 2 Preparation of 3D Biomacromolecule Structures
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16 3 Preparation of the Molecular Structure of EDC Molecule
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16 4 Obtaining the EDC—Biomacromolecule Complexes 16 4 1 Performing Molecular Docking
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16 4 2 Refining the Complex
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16 5 Probing the Underlying Binding Mechanism of Action
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16 5 2 Analyzing Noncovalent Interactions
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16 5 3 Calculating Binding Energy
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16 6 Conclusions and Future Directions
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Chapter 17
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Abstract
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17 1 Introduction
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17 1 2 Molecular Simulation of Typical Xenobiotics Metabolism Catalyzed by P450 Enzymes
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17 1 2 2 Catalytic Cycle of P450 Enzymes and Related Common
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17 2 Method and Materials
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17 3 Results
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17 3 2 Case Studies Simulating Xenobiotic Chemical Metabolism by P450 Enzymes
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17 3 2 2 Mechanisms for Dihydroxylation of PBDEs and Dioxin
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17 3 2 3 Simulation of the Metabolism of Perfluorooctane Sulfonat
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17 3 2 4 Metabolism of Halogenated Alkanes and Alkenes Catalyzed
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17 3 2 5 Metabolism of Substituted Phenolic Compounds Catalyzed
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17 4 Conclusion and Future Directions
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Chapter 18
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Abstract
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18 1 Introduction
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18 2 Method and Materials 18 2 1 The VEGAHUBStructure
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18 2 2 The QSAR Models in VEGA
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18 2 3 The ToxRead Software
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18 2 4 The ToxWeight Software
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18 2 5 The ToxDelta Software
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18 2 6 The JANUS Software
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18 3 Results 18 3 1 The VEGA Software
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18 3 2 Other Programs for Read Across
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18 3 3 The JANUS Software
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18 4 Discussion
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18 5 Conclusion and Future Directions
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Chapter 19
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Abstract
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19 1 Introduction
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19 2 Proposed Principle of Reproducibility for In Silico Modeling and Workflows and Implementa
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19 3 Example 1 QSAR Model Building and Validation
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19 4 Example 2 Integrated Testing Strategies
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19 5 Best Practices in Data Management FAIR Principles,
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19 6 Proposed Technology Solutions for Data Processing
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19 7 Locating the Source of Irreproducibility Sub tasks and Intermediate Datasets
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19 8 Use of Software Containers
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19 9 Regulatory Acceptance Practices
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19 10 Enhancing Workflow Solutions Including Trust
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19 11 Preclinical Case Regulatory Acceptance of Workflows for Heterogeneous Knowledge Integra
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19 12 Approach to Community Assessment of Best Practice Developments
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