Bioinformatics

1 Cover

2 Foreword

3 Preface

4 Contributors

5 About the Companion Website

6 1 Biological Sequence Databases Introduction Nucleotide Sequence Databases Nucleotide Sequence Flatfiles: A Dissection Protein Sequence Databases Summary Acknowledgments Internet Resources Further Reading References

7 2 Information Retrieval from Biological Databases Introduction Integrated Information Retrieval: The Entrez System Medical Databases Organismal Sequence Databases Beyond NCBI Summary Further Reading References

8 3 Assessing Pairwise Sequence Similarity: BLAST and FASTA Introduction Global Versus Local Sequence Alignments Scoring Matrices BLAST BLAST 2 Sequences MegaBLAST PSI-BLAST BLAT FASTA Summary Further Reading References

9 4 Genome Browsers Introduction The UCSC Genome Browser UCSC Table Browser ENSEMBL Genome Browser Ensembl Biomart JBrowse Summary Further Reading References

10 5 Genome Annotation Introduction Gene Prediction Methods Ab Initio Gene Prediction in Prokaryotic Genomes Ab Initio Gene Prediction in Eukaryotic Genomes How Well Do Gene Predictors Work? Assessing Prokaryotic Gene Predictors Assessing Eukaryotic Gene Predictors Evidence Generation for Genome Annotation Gene Annotation and Evidence Generation using Comparative Gene Prediction Genome Annotation Pipelines Summary Acknowledgments Internet Resources Further Reading References

11 6 Predictive Methods Using RNA Sequences Introduction Overview of RNA Secondary Structure Prediction Using Thermodynamics Dynamic Programming Accuracy of RNA Secondary Structure Prediction Predicting the Secondary Structure Common to Multiple RNA Sequences Practical Introduction to Single-Sequence Methods Practical Introduction to Multiple Sequence Methods Other Computational Methods to Study RNA Structure Comparison of Methods Predicting RNA Tertiary Structure Summary Further Reading References

12 7 Predictive Methods Using Protein Sequences Introduction One-Dimensional Prediction of Protein Structure Predicting Protein Function Summary Further Reading References

13 8 Multiple Sequence Alignments Introduction Measuring Multiple Alignment Quality Making an Alignment: Practical Issues Commonly Used Alignment Packages Viewing a Multiple Alignment Summary References

14 9 Molecular Evolution and Phylogenetic Analysis Introduction Early Classification Schemes Sequences As Molecular Clocks Background Terminology and the Basics How to Construct a Tree Marker-Based Evolution Studies Phylogenetic Analysis and Data Integration Future Challenges References

15 10 Expression Analysis Introduction Step 0: Choose an Expression Analysis Technology Step 1: Design the Experiment Step 2: Collect and Manage the Data – and Metadata Step 3: Data Pre-Processing Step 4: Quality Control Step 5: Normalization and Batch Effects Step 6: Exploratory Data Analysis Step 7: Differential Expression Analysis Step 8: Exploring Mechanisms Through Functional Enrichment Analysis Step 9: Developing a Classifier Single-Cell Sequencing Summary Further Reading References

16 11 Proteomics and Protein Identification by Mass Spectrometry Introduction Mass Spectrometry Tandem Mass Spectrometry for Peptide Identification Sample Preparation Bioinformatics Analysis for MS-based Proteomics Proteomics Strategies Peptide Mass Fingerprinting PMF on the Web Proteomics and Tandem MS PSM Software PSM on the Web Reporting Standards Proteomics Data Repositories Protein/Proteomics Databases Selected Applications of Proteomics Summary Acknowledgments Internet Resources Further Reading References

17 12 Protein Structure Prediction and Analysis Introduction to Protein Structures How Protein Structures are Determined How Protein Structures are Described Protein Structure Databases Visualizing Proteins Protein Structure Prediction Protein Structure Evaluation Protein Structure Comparison Summary Further Reading References

18 13 Biological Networks and Pathways Introduction Pathway and Molecular Interaction Mapping: Experiments and Predictions Pathway and Molecular Interaction Databases: An Overview Pathway Databases Molecular Interaction Databases Functional Interaction Databases Strategies for Navigating Pathway and Interaction Databases Standard Data Formats for Pathways and Molecular Interactions Pathway Visualization and Analysis Network Visualization and Analysis Summary Acknowledgments Internet Resources Further Reading References

19 14 Metabolomics Introduction Data Formats Databases Bioinformatics for Metabolite Identification Multivariate Statistics Bioinformatics for Metabolite Interpretation Summary Further Reading References

20 15 Population Genetics Introduction Evolutionary Processes and Genetic Variation Allele Frequencies and Population Variation Display Methods Demographic History Inference Admixture and Ancestry Estimation Detection of Natural Selection Other Applications Summary References

21 16 Metagenomics and Microbial Community Analysis Introduction Why Study the Microbiome? The Origins of Microbiome Analysis Metagenomic Workflow General Considerations in Marker-Gene and Metagenomic Data Analysis Marker Genes Metagenomic Data Analysis Other Techniques to Characterize the Microbiome Summary Further Reading References

22 17 Translational Bioinformatics Introduction Databases Describing the Genetics of Human Health Prediction and Characterization of Impactful Genetic Variants from Sequence Computing with Patient Phenotype Using Data in Electronic Health Records Informatics and Precision Medicine Ethical, Legal, and Social Implications of Translational Medicine Summary References

23 18 Statistical Methods for Biologists Introduction Descriptive Representations of Data Statistical Inference and Statistical Hypothesis Testing Summary Acknowledgments Internet Resources Further Reading References

24 Appendices1.1 Example of a Flatfile Header in ENA Format 1.2 Example of a Flatfile Header in DDBJ/GenBank Format 1.3 Example of a Feature Table in ENA Format 1.4 Example of a Feature Table in GenBank/DDBJ Format 6.1 Dynamic Programming Reference

25 Glossary

26 Index

27 End User License Agreement

1 Chapter 1 Table 1.1 Indicating locations within the feature table.

2 Chapter 2 Table 2.1 Entrez Boolean search statements.

3 Chapter 3 Table 3.1 Selecting an appropriate scoring matrix. Table 3.2 BLAST algorithms. Table 3.3 Main FASTA algorithms.

4 Chapter 7Table 7.1 Disorder prediction performance.Table 7.2 Performance of selected gene ontology term prediction methods in CAFA2...

5 Chapter 8Table 8.1 Aligner performance on BAliBASE3 benchmark.

6 Chapter 9Table 9.1 Some common software packages implementing different phylogenetic anal...

7 Chapter 11Table 11.1 List of common sources of protein sequences (used in FASTA format).Table 11.2 Standard search parameters used with sequence database search engines...

8 Chapter 12Table 12.1 Relationship between backbone root mean square deviation (RMSD, i...

9 Chapter 14Table 14.1 A list of freely available molecular editors and visualization tools.Table 14.2 A list of open access chemical, spectral, pathway, and metabolomic da...

10 Chapter 15Table 15.1 Examples of genes that have undergone natural selection in human popu...

11 Chapter 17Table 17.1 Examples of commonly used biomedical ontologies and terminologies in ...

12 Chapter 18Table 18.1 Common parametric statistical tests and their non-parametric equivale...

1 Chapter 1 Figure 1.1 The landing page for ENA record U54469.1, providing a graphical vie... Figure 1.2 Results of a search for the human heterogeneous nuclear ribosomal p... Figure 1.3 The Subcellular location and Pathology & Biotech sections of ... Figure 1.4 The Feature viewer rendering of the record for the human heterogene... Figure 1.5 Expanding the PTM, Structural features, and Variants sections withi...