rasmus group presentation

8/14/2019 Rasmus Group Presentation

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A phylogeographic

distance metric forProject leader: Dr Rasmus Hovmoller

Group members:

John Christensen, Shishi Luo, Jacob Porter,


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Talk outline

Project background and goals

Theory and calculations

Results Conclusions


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Influenza

H5N1 Endemic in bird population

Bird-to-human transmission possible

H3N2 Seasonal flu

Human-to-human transmission only


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Influenza

Wild aquatic birds,reservoir for allinfluenza subtypes

Domestic fowl, eg Humans, eg H3N2


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Global distribution of H5N1 andH N2


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Goal

To compare and contrast the patternsof geographic spread of two types ofinfluenza. calculate a statistic for correlation

between the distance between the virusisolates in the phylogenetic tree(patristic distance) and their actualgeographical distances.


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Goal

Create datasets

Make trees

Calculate patristic distances between

all pairs of sequences Collect geographic metadata

Calculate geographic distances

between all pairs of sequences Calculate correlation coefficient and

determine significance


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Databases and software

Genetic data from GenBank

Phylogenetic trees generated in RAxML, TNT, Mr

Bayes

Integrative Tree of Life (iTOL) to visualize trees Excel, Unix to manipulate data

Patristic distances calculated in Matlab

Geographic data (longitude, latitude) fromGenbank data


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Types of phylogenetic trees

Parsimony tree is the tree thatrequires the least evolutionarychange to explain given data

Maximum likelihood tree is the treewhich has the maximum likelihoodover all possible topologies under the

specified evolution model


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Parsimony

Optimality criterion: search for most

simple tree

Equal branch lengths

Doesn't work for horizontal gene transfer

Doesn't show genes lost during evolutionprocess


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Maximum Likelihood

- Evolution is characterized by acontinuous Markov chain

- Evolution model is a substitution ratematrix

- Branch lengths show geneticdistances

- Doesnt work with big datasets


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Improving of Maximum likelihood

(mixed model):

- Applying maximum likelihood onreasonable randomized parsimony

starting trees

- Using loop-level parallelism in thelikelihood functions


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H3N2 ML vs. parsimony


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H5N1 ML vs. parsimony


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Calculating correlation

Patristic distance Geographic distance

B

C

(Assume all branch

B


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Geographic

z

d=cos-

d is the shortestdistancebetween two pointsalongthe surface of thesphere.

corresponds tolatitude corresponds tolongitudeand is the anglebetween the

prime meridian and a


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Testing the significance of

GCC does not have same null-hypothesis distribution as the usualPearsons correlation coefficient, r

Use permutation distribution instead Since data set large, used random

sample of permutations

2774! > 108000

1646! >H

H


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Testing the significance of

H0: no significant correlation

H1: significant positive correlation

Reject H0 for sufficiently small p-value.

P-value: proportion of permutation GCC> observed GCC


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Smal

f

GCObserved

f

GCObserved

f

GCObserved

Easy to calculate

exact p-value

Medium

n

Computationallintensive to

Large n

p-value should beestimated

p-


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P Value Computation:

Non-standardized GCC

Permuted non-

Phillip Good. Permutation, Parametric, and Bootstrap Tests ofHypotheses. 3rdEdition. Springer: 2005Critchlow, et al. Some Statistical Methods for PhylogeneticTrees withApplication to HIV Disease. Mathematical and Computer Modeling 32


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P Value Computation: R# X, Y are the matrices to correlate

# perm is a permutation of row indices computed with the Rsample function# n is the number of rows of the matrix

covPerm


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P Value Computation:


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Asia Scatter


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Asia Scatter


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H3N2 phylogeny colored by


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H5N1 Ph l ith G hi


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H5N1 Phylogeny with GeographicL ti n


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H3N2 Ph logen ith Geographic


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H3N2 Phylogeny with GeographicL ti n


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Conclusions


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H5N1

Conclusion:

There is no significant relationshipbetween patristic distance andgeographical distance.

Explanation:(1)Its bird flu. Its much easier for birds

to migrate among countries of Asia.

(2)The H5N1 strain is fast-mutating.

1. The Asian subset of data


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Conclusion:

There is some relationship between

two kinds of distance. Explanation:

Its a human influenza virus. The

migration of humans is not frequentamong countries of Asia.

H3N2


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ConfusingH5N1

Maximum Likelihood tree: norelationship.

Parsimony tree: some

relationship.H3N2

Maximum Likelihood tree: no

2. The global set of data


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H5N1: no significantrelationship

H3N2: some relationship

he result of Europeansubset of data is

3. The European subset of


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Tree algorithms:

1) Parsimony tree: set all branchlengths equal to 1.

2) Maximum likelihood tree: Its

computational intensive, we haveto stop it before finding the besttree.

Hypothesis Test: We sampled avery small proportion of the


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Our results are consistent in smalldata sets:

H5N1: no significant relationship

H3N2: some relationship

Thus, they are persuasive.

On the other hand, the result forglobal data set is confusing, we needto do further research.

Conclusion


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Questions?

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