The Applied Genomic Epidemiology Handbook
CZ Biohub Rapid Response Resources
Dedication
Authors
Contributors
Preface
For whom is this handbook written?
How should you read this handbook?
Welcome to The Applied Genomic Epidemiology Handbook
1
The Value of Pathogen Genomics in Applied Epidemiology
1.1
The Value of Genomic Epidemiology for Surveillance
1.2
The Value of Genomic Epidemiology for Outbreak Response
1.3
The Value of Retrospective Data
2
Fundamental Theory in Genomic Epidemiology
2.1
The Overlapping Timescales of Pathogen Evolution and Pathogen Transmission
2.1.1
Viral Diversity Accumulates Over the Course of a Single Individual’s Infection
2.1.2
Stochasticity and Selection Influence Variant Frequency Within an Infection
2.1.3
When a Transmission Event Occurs, the Within-Host Viral Diversity of the Infector is Sampled and Transmitted to the Recipient
2.1.4
Consensus Genomes Provide a Summary of the Within-Host Diversity
2.2
Terminology for Describing Changes in Genetic Sequences
2.3
Mutation Rates, Evolutionary Rates, and the Molecular Clock
2.4
Multiple Sequence Alignment
2.5
Phylogenetic Trees
2.5.1
What is a Phylogenetic Tree?
2.5.2
Assessing and Reading a Phylogenetic Tree
2.5.3
Temporally Resolved Phylogenetic Trees
2.6
The Transmission Tree does not Equate the Phylogenetic Tree
2.7
Why is Sequencing Better at Dismissing Links Than Confirming Them?
2.7.1
How Many Mutations are Enough to Rule Linkage Out?
3
Sample Selection
3.1
Representative Sampling
3.2
Targeted Sampling
3.3
Sample Selection
3.4
Contextual Data
3.4.1
Contextual Data as a Backdrop
3.4.2
Contextual Data as Controls
4
Public Health Use Cases of Genomic Epidemiology
4.1
Assessing Epidemiologic Linkage Between Cases
4.1.1
Fundamental Principles to Draw Upon
4.1.2
How Should You Sample?
4.1.3
Tools and Approaches You Can Use to Explore the Question
4.1.4
Caveats, Limitations, and Ways Things Go Wrong
4.1.5
Relevant Case Studies
4.2
Exploring Relationships Between Cases of Interest and Other Sequenced Infections
4.2.1
Fundamental Principles to Draw Upon
4.2.2
How Should You Sample?
4.2.3
Tools and Approaches You Can Use to Explore the Question
4.2.4
Caveats, Limitations, and Ways Things Go Wrong
4.2.5
Relevant Case Studies
4.3
Estimating the Start and Duration of an Outbreak
4.3.1
Fundamental Principles to Draw Upon
4.3.2
How Should You Sample?
4.3.3
Tools and Approaches You Can Use to Explore the Question
4.3.4
Caveats, Limitations, and Ways Things Go Wrong
4.3.5
Relevant Case Studies
4.4
Assessing How Demographic, Exposure, and Other Epidemiological Data Relate to a Genomically Defined Outbreak
4.4.1
Fundamental Principles to Draw Upon
4.4.2
How Should You Sample?
4.4.3
Tools and Approaches You Can Use to Explore the Question
4.4.4
Caveats, Limitations, and Ways Things Go Wrong
4.4.5
Relevant case studies
5
Case Studies in Applying Genomic Epidemiology
5.1
Are Cases of the Same Variant of Concern Lineage Linked?
5.2
Evaluating an Intake Screening Program to Prevent Introduction of SARS-CoV-2 to Prisons
5.3
Identifying, Assigning, and Investigating a New SARS-CoV-2 Lineage in Lithuania
5.4
Estimating When the Zika Virus Epidemic Began in Colombia
6
Tools and Methods for Applied Genomic Epidemiological Analysis
6.1
Phylogenetic Placements
6.1.1
UShER
6.1.2
Nextclade
6.2
Phylogenetic Trees
6.2.1
Nextstrain
6.2.2
IQ-TREE
6.2.3
RAxML
6.2.4
BEAST
6.3
When Should I Use a Phylogenetic Tree Versus a Phylogenetic Placement?
6.4
Selecting Contextual Data for Phylogenetic Tree Analyses
6.5
Notes About Node Ages in Temporally Resolved Trees
7
A Deeper Dive into Viral Genomic Complexity
7.1
Recombination
7.2
Segmented Genomes and Reassortment
7.2.1
Considerations for Analysis
7.3
Hypermutation
7.3.1
Handling Variable Mutation Rates with Relaxed Molecular Clocks
7.4
Diversity of RNA Virus Genome Organizations
7.4.1
Ambisense
7.4.2
Reverse Complementarity
7.4.3
Splicing
8
Genomic Epidemiology of Bacteria
8.1
Bacterial Mechanisms for Generating Genetic Diversity
8.1.1
How Does Horizontally Acquired DNA Get into the Bacterial Cell?
8.1.2
Integration of Horizontally Acquired DNA into the Chromosome
8.1.3
Acquisition and Exchange of Extrachromosomal DNA
8.2
A Brief Note About Bacterial Population Structure
8.3
Bacterial Sequence Typing
8.4
Defining Bacterial Genomic Elements
8.4.1
Core Genome
8.4.2
Accessory Genome
8.4.3
Pangenome
8.5
Bacterial Genome Sequencing and Assembly
8.5.1
Considerations for Long-Read Sequencing Data
8.6
A Practical Workflow For Bacterial Genomic Epidemiology
8.7
Intrahost Diversity And Implications For Inferring Transmission
8.8
Investigation of Transmission
8.9
Conclusions
References
Published with bookdown
References
Dedication
For the mentors we’ve had,
And the mentors we hope to be.
