Epidemiology Flashcards
What is the basic reproductive number (R0)?
the number of secondary infections resulting from introduction of a single infected individual
the outcome of an epidemic depends on R0
–> R0 < 1 = epidemic dies out
–> R0 > 1 = epidemic grows
What are 3 categories of people taken into account when modelling an epidemic?
- susceptible
- infected
- recovered
What are the different types of mutations a pathogen can obtain?
- mutations in nucleotide only
- mutations that change amino acid
- insertions and deletions
- recombination & gene transfer
What is molecular phylogenetics?
the use of molecular data to construct phylogenies
- a phylogeny is a diagram representing the ancestral relationships among characters or genetic sequences
- phylogenetics looks for homology as evidence for common ancestry
- diagrams = trees
–> these are constructed to be able to look at the rates of evolution
What are the differences in evolutionary rates of different pathogens?
RNA viruses
–> fast rate of replication, error prone
DNA viruses
–> slower rate of replication, more conserved
bacteria
–> v slow , but evolution originates mostly from HGT, not from point mutations
parasite
–> v slow
fungi
–> can become resistant to anti-fungals very quickly
What is the structure of a phylogenetic tree?
root
–> origin
internal node
–> hypothetical ancestor
terminal node (leaf)
–> most recent species/strain
clade
–> a group of organisms that includes an ancestral species and all of its descendants, representing a single branch or lineage in the evolutionary history of the organisms being studied
What are rooted trees?
- have a single node that represents a point in time that is earlier than any other node
- have directionality (nodes can be ordered in terms of earlier or later)
- distance between two nodes is represented along the x-axis only (y is meaningless, purely for presentation)
- virus trees can be presented and measure in substitutions per site
What are unrooted trees?
- no directionality
–> do not know if a node is earlier or later than another node - distance along branches directly represents node distance
–> eg genetic distance
What is needed to build a rooted phylogenetic tree?
- sequence data (nucleotide or amino acids)
- a substitution model (also influences branch lengths)
- ability to determine branching order
1 & 2 can be used to build an unrooted tree
What is a substitution model?
- substitution mutations occur between sequences
- some types of substitutions might be more common than others (eg A-G transition)
- therefore, there are different models to reflect this, these specify:
–> the base frequencies
–> the rate of transitions (eg A-G) and transversion (eg G-C)
–> whether there is site to site rate variation eg the proportion of sites which are totally conserved (no changes) or hyper variable
Give an example of a substitution model.
General Time Reversible Model (GTR)
a complex model which states there is unequal base frequencies and all substitution types occur at different rates
What are clustering algorithms?
- the algorithms are v simple and fast
- progressively joins the two closest sequences (or ancestral sequences)
–> eg neighbour joining algorithm
What are optimisation algorithms?
- define an explicit score or goodness of each tree
- try to find the (one) tree which optimises this criterion by swapping parts
–> eg maximum likelihood
How is a time scale added to a phylogenetic tree?
adding a molecular clock
by defining the rate of mutation, a time scale can be added
eg 1 mutation per month
How can it be known who infected who?
next generation sequencing (NGS) can give an idea of who infected whom, but evidence is not generally strong or conclusive
can analyse collections of links between individuals
–> genetic clusters: sequences from samples are genetically similar
similar sequences have recent time to most recent common ancestor (TMRCA)
