Video 2.3: Phylogenetics

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From the course by The University of Hong Kong

Epidemics

27 ratings

The University of Hong Kong

Epidemics

27 ratings

“If history is our guide, we can assume that the battle between the intellect and will of the human species and the extraordinary adaptability of microbes will be never-ending.” (1) Despite all the remarkable technological breakthroughs that we have made over the past few decades, the threat from infectious diseases has significantly accelerated. In this course, we will learn why this is the case by looking at the fundamental scientific principles underlying epidemics and the public health actions behind their prevention and control in the 21st century. This course covers the following four topics: 1. Origins of novel pathogens; 2. Analysis of the spread of infectious diseases; 3. Medical and public health countermeasures to prevent and control epidemics; 4. Panel discussions involving leading public health experts with deep frontline experiences to share their views on risk communication, crisis management, ethics and public trust in the context of infectious disease control. In addition to the original introductory sessions on epidemics, we revamped the course by adding: - new panel discussions with world-leading experts; and - supplementary modules on next generation informatics for combating epidemics. -------------------------------------------------------- (1) Fauci AS, Touchette NA, Folkers GK. Emerging Infectious Diseases: a 10-Year Perspective from the National Institute of Allergy and Infectious Diseases. Emerg Infect Dis 2005 Apr; 11(4):519-25. What you'll learn - Demonstrate knowledge of the origins, spread and control of infectious disease epidemics - Demonstrate understanding of the importance of effective communication about epidemics - Demonstrate understanding of key contemporary issues relating to epidemics from a global perspective

From the lesson

Theme One: Origins (Emergence and ecology of infectious diseases)

Week 2: Introduction1:28

Video 2.1: Ecology and evolution of infectious diseases8:54

Video 2.2: Emerging infectious diseases at the human-animal interface8:21

Video 2.3: Phylogenetics9:35

Video 2.4: Emergence of highly pathogenic H5N1 avian influenza virus in Asia10:04

Video 2.5: Emergence of the H7N9 influenza A virus in China9:14

Video 2.6: Swine Influenza and the 2009 Pandemic H1N16:51

Meet the Instructors

Gabriel M. Leung (HKU)
Dean
Li Ka Shing Faculty of Medicine
Joseph T. Wu (HKU)
Associate Professor
Li Ka Shing Faculty of Medicine
Kwok-Yung Yuen (HKU)
Professor
Li Ka Shing Faculty of Medicine
Tommy Lam (HKU)
Assistant Professor
Li Ka Shing Faculty of Medicine
Maria Huachen Zhu (HKU)
Associate Professor
Li Ka Shing Faculty of Medicine
Guan Yi (HKU)
Chair Professor
Li Ka Shing Faculty of Medicine
Benjamin Cowling (HKU)
Professor
Li Ka Shing Faculty of Medicine
Thomas Abraham (HKU)
Associate Professor
Journalism and Media Studies Centre
Mark Jit (LSHTM)
Professor
Department of Infectious Disease Epidemiology
Malik Peiris (HKU)
Chair Professor
Li Ka Shing Faculty of Medicine
Marc Lipsitch (Harvard)
Professor
Department of Epidemiology

In this session, I will first talk

about what is a phylogenetic tree,

and then how do we use phylogenetic trees

to study an epidemic of infections disease.

Phylogenetics is a field studying the evolutionary

relationships of organsisms using their biomarkers,

such as DNA sequences.

A phylogenetic tree is a tree-like diagram

illustrating such evolutionary relationships.

Here's an example of a phylogenetic tree built

from the DNA sequences of these organisms.

The tree shows a long evolutionary distance between

humans and cattle, passing through the root of the tree.

In contrast, a human is evolutionarily closer to a

chimpanzee, which shares a more recent common ancestor.

The evolutionary relationships and the branch lengths

in the tree, largely reflect the similarity

between the DNA sequences of these organisms.

A phylogenetic tree can be shown

in different visual presentations.

Tree branches can be straight and slanted,

they can also be rectangular, or even circular.

Although they look different, they illustrate

the same evolutionary relationships.

There are a number of computational methods to build

a phylogenetic tree from genetic sequences, such as neighbour-joining,

maximum likelihood search, and Bayesian inference.

Let's go through the neighbour-joining algorithm.

We compare each pair of DNA sequences

to compute their genetic distances.

The two closest sequences are first joined, their

common genetic distance to the other sequences is recomputed.

Then the next two closest sequences are joined,

and the algorithm iterates until a complete tree

is built by joining all the sequences.

Similar to higher organisms, pathogens,

such as viruses, mutate and evolve when they

infect and transmit among their hosts.

Their evolutionary relationships reflect their

transmission history in the host population.

Therefore, building the phylogenetic tree

of the pathogens in an epidemic helps us understand

the development of the disease in the past.

When an infectious disease starts from the index patient,

and spreads through the population, some infected cases

are registered by the public health surveillance.

If the specimens containing the pathogens

are also sampled, their genome sequences

can be obtained by laboratory process.

For example, these sequences are obtained in

surveillance, and built into a phylogenetic tree.

This tree shows that the sequences are separately clustered

into two lineages, suggesting that they

resulted from two separate clusters of transmissions.

As a conventional approach, we can also trace

the contact and travel history of the patients,

to learn about the disease transmission history.

However, when the surveillance system misses out some infected

patients in the transmission chain, this method becomes

very difficult to complete the transmission history.

This often happens for diseases that cause

no or mild symptoms in some individuals.

In contrast, phylogenetic approach is less affected

by this problem, because the transmission by even

symptomless patients has already left their

genetic footprints in the pathogen genomes,

so the transmission history can still be constructed

with a relatively lower sampling ratio in the surveillance.

Phylogenetic analysis has been widely used

to study the development of an epidemic.

An example is the SARS outbreak in the year 2003.

This epidemic appears to start in Guangdong,

then spread to Hong Kong and soon other countries,

including Vietnam, Canada, Singapore, and Taiwan.

Phylogenetic analysis of the virus gives clues to the

source and relation of the outbreaks in different regions.

SARS virus genome sequences from different regions

were built into a phylogenetic tree shown here.

Below that is a transmission history inferred from

the contact and travel history of the SARS patients.

Soon after the initial outbreaks in Guangdong,

the virus spread to Beijing, which is supported by the

early divergence of the Beijing sequences in the tree.

In Hong Kong some early cases are traced to be

sporadic cases imported from Guangdong.

The disease did not spread through until an index patient

from Guangdong traveled to Hong Kong, and passed the virus

to a number of people staying in the same hotel with him.

These secondary patients, many of them who are visitors,

subsequently transmitted the virus to their

home country when they traveled back.

The phylogenetic tree supports this massive spread

as we see in the tree, the viruses from these countries

are clustered into the same lineage.

One infected Singaporean visitor may be the source

of the local outbreak in his country, because in the tree,

his virus sequence clusters with other

viruses from the local outbreak.

Taiwan also has SARS outbreaks.

In the tree, some Taiwan viruses are clustered with

the viruses from Amoy Gardens residents in Hong Kong,

and this is in line with the finding that an infected

Amoy Gardens resident had traveled to Taiwan during that time.

Some other Taiwan viruses form separate

clusters in the tree, suggesting additional

disease introduction to the country.

An epidemic can be generated when a novel

pathogen jumps from animals to humans,

and establishes efficient transmissions.

Tracing the animal source for such a zoonotic outbreak

informs us to which animal we should reduce our exposure,

and hence prevent our population

from getting the pathogen again.

This is important to control an epidemic caused by zoonosis.

To achieve this, in addition to the

pathogen sequences we obtain from the epidemic,

we also need to survey the animals that possibly

carry the same or related pathogens.

With all pathogen sequences from the human patients and

animals, we can build a phylogenetic tree of them to

identify which animal pathogen is the most

closely connected to the human ones, which is

the possible animal origin of the epidemic.

Such phylogenetic analysis has been applied to study the

human infections of novel H1N1 influenza in the year 2009.

In April, a 10-year-old boy in California

was tested positive for influenza.

Molecular diagnosis and sequencing showed

that the influenza virus is new to humans.

Further cases were reported in California and Texas.

Soon after that the disease spread all over the world.

To set up a phylogenetic analysis to trace the

disease origin, we have the novel H1N1 virus sequences.

We also include sequences of the human seasonal influenza.

And the influenza virus found in birds, pigs, and horses.

First, the tree shows that the novel H1N1 virus is

genetically distant to the seasonal human influenza,

which means that this virus did not directly evolve

from the preexisting human influenza.

Second, in the tree, this novel virus is

clustered with the swine influenza viruses,

suggesting that the virus came from pigs.

Phylogenetic analysis of all influenza gene sequences,

lead to the same conclusion of swine origin,

therefore, this novel disease is also called swine flu.

In summary, phylogenetic tree is used to delineate

the evolutionary relationship of the pathogens

from their genetic sequences.

It is a useful tool to study the transmission history

and trace the animal source of an epidemic.

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