Post-genomic approaches in drug and vaccine development / edited by Kishore R. Sakharkar, Meena K. Sakharkar, and Ramesh Chandra.

Format:

Book

Contributor:

Sakharkar, Meena K., editor.

Sakharkar, Kishore R., editor.

Chandra, Ramesh, 1957- editor.

Series:

River publishers series in research and business chronicles: biotechnology and medicine ; Volume 5.

River Publishers Series in Research and Business Chronicles: Biotechnology and Medicine ; Volume 5

Language:

English

Subjects (All):

Drug development.

Drugs--Design.

Drugs.

Physical Description:

1 online resource (451 pages) : illustrations (some color), charts, tables, graphs.

Edition:

1st ed.

Place of Publication:

Gistrup, Denmark : River Publishers, [2015]

Summary:

It is equally important to understand the labors and limitations in integrating clinical phenotypes with genomic, transcriptomic, proteomic and metabolomic approaches. This book focuses on some key advances in the field.

Contents:

Cover

RIVER PUBLISHERS SERIES IN RESEARCHAND BUSINESS CHRONICLES: BIOTECHNOLOGYAND MEDICINE

Title Page

Copyright

Contents

Series Note

Preface

Acknowledgements

List of Figures

List of Tables

1. Drug Discovery: Diseases, Drugs and Targets

1.1 Introduction

1.2 Drug Discovery

1.2.1 Phase 1 Clinical Trial: Perform initial human testing in a small group of healthy volunteers

1.2.2 Phase 2 Clinical Trial:Test in a small group of patients

1.2.3 Phase 3 Clinical Trial:Test in a large group of patients to show safety and efficacy

1.3 Drug and Targets

1.3.1 Drugs/target and Targets/drug

1.4 Disease Genes - Targets and Drugs

1.5 Conclusions

References

2. Target Identification and Validation in Microbial Genomes

2.1 Introduction

2.2 Strategies for Target Identification in Silico

2.2.1 Essential genes

2.2.2 Conserved genes

2.2.3 Disordered proteins

2.2.4 Load point &amp

Choke points, and FBA

2.2.5 Virulence proteins

2.2.6 In vitro experiments

2.2.7 Overlapping genes/proteins

2.2.8 Fusion proteins

2.2.9 Hub proteins and networks

2.2.10 Membrane proteins, uncharcterised essential genes, species specific genes as targets

2.2.11 Structural genomics

2.2.12 Selectivity

2.2.13 Target prioritization in completely sequenced Pseudomonas aeruginosa genomes

2.2.14 Genomes/Conserved proteins/Non-human homologs

2.2.15 Disordered regions and Virulent factors

2.2.16 Identification of unique enzymes in unique and shared pathways

2.2.17 Comparison of unique enzymes to essential gene data

2.2.18 Choke points

2.2.19 FBA

2.2.20 Mutagenesis

2.3 Conclusions

3. A Prioritization Analysis of Disease Association by Data-mining of Functional Annotation of Human Genes

3.1 Introduction

3.1.1 Genetics underlying disease.

3.1.2 The era of genomics

3.1.3 Genes and their function

3.1.4 Disease gene prioritization

3.1.5 Beyond genes - functional annotation of the entire genome

3.2 Definition of a Gene

3.3 Data-Mining Functional Annotation

3.4 Experimental Sources of Functional Annotation

3.5 Inferred Functional Annotation Through Sequence Similarity

3.6 High Throughput Candidate Disease Gene Prioritization Through Semantic Discovery

3.6.1 The BioOntological Relationship Graph (BORG) Semantic Database

3.6.2 Mining the BORG Database Through Semantic Querying

3.6.2.1 Ontology seeded queries

3.6.2.2 Annotation retrieval

3.6.2.3 Path-based transitive association queries

3.7 Conclusions

4. Genomics-Guided Discovery of Novel Therapeutics of Actinobacterial Origin

4.1 Introduction

4.2 Alternative Culturing Methodologies for Diversification of Microbial Natural Products

4.2.1 Exploring naive ecosystems for sample collections

4.2.2 Acknowledging significance of microbial symbiosis

4.2.3 Culture independent sampling approaches

4.2.4 Manipulating culture conditions for maximizing natural product biosynthesis by cultured microorganisms

4.2.5 Microbial co-culturing for improved synthesis of natural products

4.3 Genetics/Genomics-Guided-Approaches for Diversification of Microbial Natural Products

4.3.1 Hetrologous expression of environmental DNA

4.3.2 Whole genome sequencing and data mining

4.3.3 Genome scanning with genome sequence tags

4.3.4 Homology-guided metagenomic screening

4.3.5 Genomics-guided induction of cryptic gene clusters

4.3.5.1 Ribosome engineering

4.3.5.2 Modulating dasR activity

4.3.6 Genomics-guided combinatorial biosynthesis of novel microbial natural products

4.4 Conclusions

5. Chemogenomics Approach to Computer Aided Drug Discovery.

5.1 Introduction

5.2 Description of Protein Ligand Spaces

5.2.1 Protein space

5.2.2 Ligand space

5.3 Applications

5.3.1 Target fishing

5.3.1.1 Similarity searching in chemical databases

5.3.1.2 Data-mining in annotated databases

5.3.1.3 Molecular docking

5.3.2 Prediction of The Bioprofiles of Drugs

5.3.3 Drug Repurposing

5.4 Conclusions

6. Network Biology Methods for Drug Repositioning

6.1 Introduction

6.2 Principles of Drug Repositioning Strategies

6.2.1 Screening of Related but Heterogeneous Knowledgebases

6.2.2 Pharmacopeia Scanning

6.2.3 Phenotype-centric Screening

6.3 Computational Network Approaches for Drug Repositioning

6.4 Network Analysis Concepts

6.4.1 Measures of Node Centrality

6.4.1.1 Degree

6.4.1.2 Betweenness centrality

6.4.1.3 Closeness centrality

6.4.1.4 Eigenvector centrality

6.4.2 Shortest Path Length

6.4.3 Network Clustering Coefficient

6.4.4 Network Density

6.4.5 Sub-networks, Modules and Communities

6.5 Network Biomedicine

6.5.1 Case Studies

6.5.1.1 Mantra: mode of action by network analysis

6.5.1.2 Disease profiles and protein interactions mining

6.5.1.3 Heterogeneous network clustering

6.6 Conclusions

7. Hypothesis Driven Multi-target Drug Design

7.1 Introduction

7.1.1 Molecular docking

7.1.1.1 Docking of proposed hybrid compounds at the ATP binding sites of GyrB/ParE

7.1.1.2 Docking of proposed hybrid compounds at the pterin binding site of DHPS

7.1.1.3 Docking of proposed hybrid compounds at the folate binding site of DHFR

7.1.2 Molecular dynamics simulations

7.2 Electronic Property Analyses of all the Designed Hybrid Compounds

7.3 In Silico Calculations of Physico-Chemical, Drug-Likeness and Toxicity Risk Analyses

7.4 Conclusions

References.

8. Genomics in Vaccine Development

8.1 Introduction

8.2 Genomics in Vaccine Development

8.2.1 Characterization of Pathogens

8.2.2 Characterization of the Host Immune System

8.2.2.1 Personalized vaccines

8.3 Application

8.3.1 Host Diversity Characterization

8.3.2 Pathogen Diversity Characterization

8.3.3 Vaccine Target Prediction

8.3.3.1 T-cell epitopes

8.3.3.2 B-cell epitopes

8.3.4 Selection of Vaccine Targets

8.4 Reverse Vaccinology Pipeline for Viral Pathogens

8.4.1 Step 1: Pathogen and Host Characterization

8.4.2 Step 2: Cataloguing Potential Antigen

8.4.3 Step 3: Identification of Potential T-cell Epitopes

8.4.4 Step 4: Epitope Conservation Analysis

8.4.5 Step 5:Validation

8.5 Conclusions

9. Toward the Computer-aided Discovery and Design of Epitope Ensemble Vaccines

9.1 Exordium

9.2 The Informatics of Epitology

9.3 Epitope Vaccines: Current Status

9.3.1 Alzheimer's Disease

9.3.2 HIV

9.3.3 Malaria

9.3.4 Cancer

9.3.5 Influenza

9.4 The in Silico Design of Epitope Ensemble Vaccines: A Critique

9.5 Conclusions

10. Vaccine Discovery and Translation of New Vaccine Technology

10.1 Introduction

10.2 Classical Vaccinology Approaches

10.2.1 Live Attenuated and Inactivated Whole Organism Vaccines

10.2.2 "Subunit" and "extract" vaccine

10.3 Identification of New Vaccine Candidates through Innovative Genome Based Technologies

10.3.1 Reverse Vaccinology

10.3.2 Pan-genomic reverse vaccinology approach

10.3.3 Functional Genomics Approaches in Vaccine Development

10.4 Rational Design of Novel Vaccine Antigens Based on Integrated Genomic and Structural Information

10.4.1 Design of Chimeric Vaccine Components

10.4.2 Structural Vaccinology Approach to Design Novel Antigens

10.5 Conclusion and Future Perspectives.

References

11. Outer Membrane Proteins as Potential Candidate Vaccine Targets

11.1 Introduction

11.1.1 Outer Membrane Proteins

11.1.1.1 Lipoproteins

11.1.1.2 Integral membrane proteins

11.1.2 OM lipids

11.1.2.1 Phospholipids

11.1.2.2 Lipopolysaccharides (LPS)

11.1.3 OMP Biogenesis and Assembly

11.1.4 Lipoprotein Transport

11.2 Evaluation of Outer Membrane Proteins as Vaccine Candidates

11.2.1 OMP in Bacterial Pathogenesis and Virulence

11.2.2 Vaccines Against Intracellular and Extracellular Bacteria - Induction of Different Types of Protective Immunity

11.2.3 Leptospirosis

11.2.4 Porphyromonas gingivalis

11.2.5 Pseudomonas aeruginosa

11.2.6 Burkholderia pseudomallei

11.2.7 Neiserria meningitidis

11.2.8 Haemophilus influenzae

11.2.9 Ehrlichiosis

11.2.10 Brucella

11.3 Genomics and Functional Genomics in OMP-Based Vaccine Development

11.4 Conclusions

12. Systems Biology Approaches to New Vaccine Development

12.1 Introduction

12.2 Systems Biology for Vaccine Development

12.2.1 Integration of Biological Data

12.2.2 Prediction of Vaccine Efficacy

12.2.3 Identification of Novel Immune Regulation Mechanisms

12.3 Technologies

12.3.1 Genomics

12.3.2 Proteomics

12.3.3 Bioinformatics

12.3.3.1 Databases

12.3.3.2 Tools

12.3.3.3 Computational models

12.4 Challenges

12.5 Examples

12.5.1 Yellow Fever Vaccine YF-17D

12.5.2 Seasonal Influenza Vaccine

12.5.3 Tuberculosis Vaccine

12.6 Conclusions

13. Inhibition of Virulence Potential of Vibrio Cholerae by Herbal Compounds

13.1 Introduction

13.2 Microbiology of Vibrio Cheolrae

13.2.1 Mechanism of Infection

13.3 Global Status of Cholera

13.4 Introduction

13.4.1 Cholera Toxin

13.4.1.1 Structure and function

13.4.2 Toxin coregulated pilus (TCP).

13.4.3 Adhesin Factors (Accessory Colonization Factors).

Notes:

Includes index.

Includes bibliographical references at the end of each chapters and index.

Description based on print version record.

ISBN:

1-000-79239-0

1-00-333909-3

1-000-79571-3

1-003-33909-3

87-93102-85-2

9781003339090

OCLC:

957125378