Abstract

Genomic analysis is a powerful tool for understanding viral disease outbreaks. Sequencing of viral samples is now easier and cheaper than ever before and can supplement epidemiological methods by providing nucleotide-level resolution of outbreak-causing pathogens. In this review, we describe methods used to answer crucial questions about outbreaks, such as how they began and how a disease is transmitted. More specifically, we explain current techniques for viral sequencing, phylogenetic analysis, transmission reconstruction, and evolutionary investigation of viral pathogens. By detailing the ways in which genomic data can help us understand viral disease outbreaks, we aim to provide a resource that will facilitate the response to future outbreaks.

Highlights

  • The Ebola virus (EBOV) outbreak in Nigeria presented a unique opportunity to compare conclusions obtained from genomic data to those determined from detailed contact tracing

  • To measure overall per-base discordance between consensus genomes produced by amplicon sequencing and hybrid capture, we considered all sites at which base calls were made in both the amplicon sequencing and hybrid capture consensus genomes of a sample, and we calculated the fraction in which the bases were not in agreement

  • We generated 203 whole genome sequences of mumps virus (MuV) from Massachusetts and 15 other states to understand the dynamics of mumps spread locally and nationally, as well as to search for mutations associated with vaccine escape

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Summary

Multiple sequence Sample 2

Viral sequences is still an area of active development. Sequence differences between viral genomes mark the evolutionary history and relationships between samples. Maximum likelihood methods [68] can calculate substitution rates given a phylogenetic tree and sampling dates It is a helpful simplification, the strict molecular clock does not always accurately model real viral evolution; evolutionary rates can vary over time, over space, or between different branches. Because the infected individual had no known Ebola virus-positive contacts, and because molecular diagnostic methods could not differentiate between outbreak lineages, whole-genome sequencing was needed to identify the most likely source of infection As shown by these examples, viral genomic sequencing can be a vital tool for detailed transmission reconstruction when contact tracing data is missing or uninformative. This is common during outbreaks, when a majority of viral genomes may be terminal branches

R -B T
GP B C E
SNPs from index from index
EBOV G
V RNA I
II-outbreak
A L last non-vaccine
5.5.22 SH HN M
Method Amplicon sequencing
MMR 1 MMR None Unknown
75 European ancestry in US samples
Findings
D Whole genome
Full Text
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