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Applications of Bayesian phylodynamic methods to the
investigation of the recent 1-7-4 PRRSv outbreak
Andres Perez, DVM, PhD
Endowed Chair of Global Animal Health and Food Safety
College of Veterinary Medicine
University of Minnesota
aperez@umn.edu
Swine Group, University of Minnesota
Moh Alkhamis
Andres Perez
Mike Murtaugh
Xiong Wang
Bob Morrison
Team work
Swine Health Monitoring Program
Four anonymous participants
Paton et al. 2005. Selection of foot and mouth disease vaccine strains- a rev
Introduction
Suppose that we have sequences from 8 farms (1 per farm)
Each square represents one nucleotide of the sequence
Paton et al. 2005. Selection of foot and mouth disease vaccine strains- a rev
Introduction
Alignment
Paton et al. 2005. Selection of foot and mouth disease vaccine strains- a rev
Matrix of (nt) differences
1 2 3 4 5 6 7
2 2
3 1 2
4 5 4 4
5 2 1 1 3
6 4 3 3 2 2
7 3 1 3 4 2 4
8 6 5 5 1 5 3 5
Paton et al. 2005. Selection of foot and mouth disease vaccine strains- a rev
(nt) Genetic distance
1 2 3 4 5 6 7
2 0.333
3 0.167 0.333
4 0.833 0.667 0.667
5 0.333 0.167 0.167
6 0.667 0.5 0.5 0.333 0.333
7 0.5 0.167 0.5 0.667 0.333 0.667
8 1 0.833 0.833 0.167 0.833 0.5 0.833
Genetic distance (GD)
GD = (nt, aa) differences / (nt, aa) compared
Probability of finding one (nt, aa) difference when two strains ar
Paton et al. 2005. Selection of foot and mouth disease vaccine strains- a rev
Phylogenetic trees
1) Because sequences theoretically split into two descendant
sequences, phylogenetic trees are typically assumed to be
bifurcating
2) Topology: branching pattern of a tree
3) Taxa: any kind of taxonomic units (eg.: virus sequences)
Unrooted tree Rooted tree
Paton et al. 2005. Selection of foot and mouth disease vaccine strains- a rev
Phylogenetic trees
If 4 taxa are being compared, there are 15 and 3
possible rooted and unrooted tree topologies,
respectively
From Nei and Kumar, 2000
Paton et al. 2005. Selection of foot and mouth disease vaccine strains- a rev
Phylogenetic trees
When 10 taxa are being compared, the number of possible
rooted topologies is 34,459,425 and the number of possible
bifurcating unrooted topologies is 2,027,025
Only one of them is the true topology
Reconstructed or inferred trees: trees built from observed
sequences
Traditional methods to infer a tree (distance, parsimony,
likelihood) ignore the associated epidemiological information
(space, time of identification, associated data)
Paton et al. 2005. Selection of foot and mouth disease vaccine strains- a rev
Bayesian phylogenetic methods
http://www.nbcnews.com/science/such-
deep-roots-you-have-how-little-red-riding-
hoods-2D11591047
http://www.plosone.org/article/in
fo%3Adoi%2F10.1371%2Fjourn
al.pone.0078871
Paton et al. 2005. Selection of foot and mouth disease vaccine strains- a rev
Bayesian phylogenetic methods
Correlation of alternative metrics of PRRSv relatedness, namely, difference (%) in
the number of nucleotides (X axis) and considering phylogenetic evolution (Y axis).
Correlation is quite bad
Phylogenetic methods
• Similarly, we can use phylogenetic methods
to infer:
– Most likely time of emergence of the strain;
– Past probability of spread between systems and
between type of farms
– Population (viral) size
Data
• 6,774 ORF 5 sequences
• January 1998 – April 2015
• 5 independent systems (coded A…E)
• Type of farm (sow, growing pig farms)
• Selected 1-7-4 PRRSv using a maximum
likelihood algorithm
Results
Some (n= 288) related
sequences (based on
ML) collected between
September 2003-March
2015
Most (n=241) are 1-7-4
sequences obtained
between Jan 2014 and
Mar 2015
Results
Increase in
population size in
2014
Results
History of spread
between systems
Results
History of spread
between types of
farms
Dynamic representation
Future plans
• Continue enrollment of systems
• Standardization and optimization of protocols
for data collection and sharing
• Implementation of analytical tools into IT
system designated by the SHIC
• Provide near real time interpretation of results
• Contribute to PRRS control at a national
scale
Thank you

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Dr. Andres Perez - Tempero-Spatial Sequence Analysis, Bayesian Phylodynamic Methods on 1-7-4 PRRSv

  • 1. Applications of Bayesian phylodynamic methods to the investigation of the recent 1-7-4 PRRSv outbreak Andres Perez, DVM, PhD Endowed Chair of Global Animal Health and Food Safety College of Veterinary Medicine University of Minnesota aperez@umn.edu
  • 2. Swine Group, University of Minnesota Moh Alkhamis Andres Perez Mike Murtaugh Xiong Wang Bob Morrison Team work Swine Health Monitoring Program Four anonymous participants
  • 3. Paton et al. 2005. Selection of foot and mouth disease vaccine strains- a rev Introduction Suppose that we have sequences from 8 farms (1 per farm) Each square represents one nucleotide of the sequence
  • 4. Paton et al. 2005. Selection of foot and mouth disease vaccine strains- a rev Introduction Alignment
  • 5. Paton et al. 2005. Selection of foot and mouth disease vaccine strains- a rev Matrix of (nt) differences 1 2 3 4 5 6 7 2 2 3 1 2 4 5 4 4 5 2 1 1 3 6 4 3 3 2 2 7 3 1 3 4 2 4 8 6 5 5 1 5 3 5
  • 6. Paton et al. 2005. Selection of foot and mouth disease vaccine strains- a rev (nt) Genetic distance 1 2 3 4 5 6 7 2 0.333 3 0.167 0.333 4 0.833 0.667 0.667 5 0.333 0.167 0.167 6 0.667 0.5 0.5 0.333 0.333 7 0.5 0.167 0.5 0.667 0.333 0.667 8 1 0.833 0.833 0.167 0.833 0.5 0.833 Genetic distance (GD) GD = (nt, aa) differences / (nt, aa) compared Probability of finding one (nt, aa) difference when two strains ar
  • 7. Paton et al. 2005. Selection of foot and mouth disease vaccine strains- a rev Phylogenetic trees 1) Because sequences theoretically split into two descendant sequences, phylogenetic trees are typically assumed to be bifurcating 2) Topology: branching pattern of a tree 3) Taxa: any kind of taxonomic units (eg.: virus sequences) Unrooted tree Rooted tree
  • 8. Paton et al. 2005. Selection of foot and mouth disease vaccine strains- a rev Phylogenetic trees If 4 taxa are being compared, there are 15 and 3 possible rooted and unrooted tree topologies, respectively From Nei and Kumar, 2000
  • 9. Paton et al. 2005. Selection of foot and mouth disease vaccine strains- a rev Phylogenetic trees When 10 taxa are being compared, the number of possible rooted topologies is 34,459,425 and the number of possible bifurcating unrooted topologies is 2,027,025 Only one of them is the true topology Reconstructed or inferred trees: trees built from observed sequences Traditional methods to infer a tree (distance, parsimony, likelihood) ignore the associated epidemiological information (space, time of identification, associated data)
  • 10. Paton et al. 2005. Selection of foot and mouth disease vaccine strains- a rev Bayesian phylogenetic methods http://www.nbcnews.com/science/such- deep-roots-you-have-how-little-red-riding- hoods-2D11591047 http://www.plosone.org/article/in fo%3Adoi%2F10.1371%2Fjourn al.pone.0078871
  • 11. Paton et al. 2005. Selection of foot and mouth disease vaccine strains- a rev Bayesian phylogenetic methods
  • 12. Correlation of alternative metrics of PRRSv relatedness, namely, difference (%) in the number of nucleotides (X axis) and considering phylogenetic evolution (Y axis). Correlation is quite bad
  • 13. Phylogenetic methods • Similarly, we can use phylogenetic methods to infer: – Most likely time of emergence of the strain; – Past probability of spread between systems and between type of farms – Population (viral) size
  • 14. Data • 6,774 ORF 5 sequences • January 1998 – April 2015 • 5 independent systems (coded A…E) • Type of farm (sow, growing pig farms) • Selected 1-7-4 PRRSv using a maximum likelihood algorithm
  • 15. Results Some (n= 288) related sequences (based on ML) collected between September 2003-March 2015 Most (n=241) are 1-7-4 sequences obtained between Jan 2014 and Mar 2015
  • 20. Future plans • Continue enrollment of systems • Standardization and optimization of protocols for data collection and sharing • Implementation of analytical tools into IT system designated by the SHIC • Provide near real time interpretation of results • Contribute to PRRS control at a national scale