SCOTTI: Inferring transmission with the Structured Coalescent - - PowerPoint PPT Presentation

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SCOTTI: Inferring transmission with the Structured Coalescent - - PowerPoint PPT Presentation

Aug 06, 2023 150 likes •349 views

SCOTTI: Inferring transmission with the Structured Coalescent Nicola De Maio, Chieh-Hsi Wu, Daniel Wilson Host information ACGTCG Time ACATCG ACGTTG CCGTTG Complications: within-host coalescent Transmission and evolution history

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SLIDE 1

Nicola De Maio, Chieh-Hsi Wu, Daniel Wilson

SCOTTI: Inferring transmission with the Structured Coalescent

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SLIDE 2

Host information

Time

CCGTTG ACGTCG ACGTTG ACATCG

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SLIDE 3

Transmission network Transmission and evolution history

Complications: within-host coalescent

Phylogenetic tree

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SLIDE 4

Complications

Time

Within-host coalescent Incomplete bottleneck Non-sampled case Multiple infections

A B C D

S1 S2 S3 S1 S1 S1 S2 S2 S3 S3 S3

Time Time Time

H1 H1 H1 H1 H2 H2 H2 H2 H3 H3 H3 H3 H1 H2 H3 H3 H1 H2 H1 H2 H3 H1 H3 H2 S1 S2 S3 S1 S2 S3 S1 S3 S3 S1 S2

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SLIDE 5

Structured coalescent

Coalescence events only within demes Migration moves single lineages between demes.

We use a recent efficient approximation to the structured coalescent: BASTA (De Maio et al 2015 PLOS Genetics).

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SLIDE 6

Phylogeography ¡with ¡BASTA ¡

  • ●
  • ●
  • 1e−03

1e−01 1e+01 1e+03 1e−06 1e−03 1e+00 1e+03 1e+06

Posterior(median(and(95%(interval( (a)(Mugra7on( (b)(Mul7TypeTree( (c)(BaStA( Migra7on(rates(ra7o( Migra7on(rates(ra7o( Migra7on(rates(ra7o(

  • ●
  • ●●
  • ●
  • ● ●
  • 1e−03

1e−01 1e+01 1e+03 1e−06 1e−03 1e+00 1e+03 1e+06

  • ●
  • ●
  • 1e−03

1e−01 1e+01 1e+03 1e−06 1e−03 1e+00 1e+03 1e+06

(((Calibra7on:(56%( ((Correla7on:(0.58( (((Calibra7on:(87%( ((Correla7on:(0.77( (((Calibra7on:(95%( ((Correla7on:(0.83(

Discrete trait (Lemey et al 2009) fast but inaccurate. Structured coalescent (Vaughan et al 2014) accurate but slow. BASTA (De Maio et al 2015) accurate and fast.

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SLIDE 7

SCOTTI

SCOTTI: Efficient Reconstruction of Transmission within Outbreaks with the Structured Coalescent

Nicola De Maio1,2, Chieh-Hsi Wu2, Daniel J Wilson1,2,3

  • Hosts (demes) have same

population size.

  • Hosts have limited lifespan.
  • No bottlenecks at transmission.
  • Lineages do not migrate together

at transmission.

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SLIDE 8

Simulated model

Didelot et al 2014 MBE. Hall et al 2015 PLOS Comput Biol.

  • Bottlenecks at transmission.
  • Lineages migrate together at

transmission.

  • Only one transmission per host.

Extension of:

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SLIDE 9

Benchmark model

  • No within-host population.
  • No within-host evolution.
  • Mutations accumulate at transmission.
  • Only one sample per host.
  • Generations of same lengths.

Jombart et al 2014 PLOS Comput Biol

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SLIDE 10

Multispecies (simulated history)

A

SCOTTI (ideal inference)

B

Outbreaker (ideal inference)

C

Time

H1 H2 H1 H3 H1 H2 H2 H3 H3 H4 H4 H4

S1.1 S1.2 S2.1 S2.2 S4.1 S4.2 S2.1 S2.2 S1.1 S1.2 S4.1 S4.2 S4.1 S1.1 S2.1

Models used

Jombart et al 2014 PLOS Comput Biol De Maio et al 2016 PLOS Comput Biol Didelot et al 2014 MBE Hall et al 2015 PLOS Comput Biol

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SLIDE 11

Simulations

Calibration 95% posterior sets Accuracy of point estimate

Outbreaker

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SLIDE 12

Simulations

Calibration 95% posterior sets Accuracy of point estimate

Outbreaker

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SLIDE 13

Simula' Mean*accuracy**

  • f*the*point*es'mate*

A*

Calibra'on* ula'on*scenario*

A* B*

Calibra'on*

Simulations

Within-host similarity

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SLIDE 14

Simulations – Running time

0" 2000" 4000" 6000"

0" 2000" 4000" 6000" 0" 2000" 4000" 6000" 0" 2000" 4000" 6000" 0" 2000" 4000" 6000" 0" 2000" 4000" 6000" 0" 2000" 4000" 6000" 0" 2000" 4000" 6000" 0" 2000" 4000" 6000" 0" 2000" 4000" 6000"

3" 5" 7" Genera4ons" 3" 5" 7" Hosts"per"genera4on"

100"s" 124"s" 118"s" 239"s" 171"s" 346"s" 233"s" 385"s" 414"s" 819"s" 314"s" 774"s" 822"s" 2021"s" 547"s" 1733"s" 1279"s" 4039"s"

1 2

1"sample"" "per"host" 2"samples"" ""per"host"

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SLIDE 15

FMDV data

0.23 . 4 4 0.62 0.21 0.16 0.20 . 1 9 . 3 7 0.43 . 5 4 . 2 3 . 1 5 . 2 5 . 3 0.11 . 3 9 0.15 0.13 0.16 . 2 6 . 4 2 . 2 2 0.37 0.16 0.11 . 1 6 . 1 6 0.17 . 1 3

IP1b 0.53 IP5 0.01 IP3b 0.00 IP3c 0.00 IP8 0.00 IP7 0.00 IP6b 0.00 IP4b 0.00 IP2b 0.25 IP2c 0.15

1/1 6/1 5/1 3/1 10/1 3/1 2/1 2/1 2/1 IP3c IP5 IP8 IP1b IP7 IP3b IP4b IP2c IP2b IP6b

SCOTTI

Cottam et al. 2008 PLOS Pathogens

Outbreaker

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SLIDE 16
  • K. Pneumoniae data

0.11 . 5 2 0.07 . 7 0.66 0.30 0.33 0.46 0.45

PMK23 PMK26 PMK18 PMK21 PMK22 PMK25 PMK24

. 6 . 1 2 0.24 . 1 3 0.23

PMK3 PMK4 PMK7 PMK5 H30 PMK1 PMK9 PMK19

0.20 . 2 8 0.27 0.06 . 2 4 0.31

PMK10 PMK12 PMK13 PMK11 PMK20 PMK15

0.06

PMK14 PMK16 PMK6 PMK17

0.5 0.5 0.5 0.5 0.5 0.5 0.51 0.49 0.26 0.250.49 0.33 0.35 0.99 0.98 1 1 0.41 0.55 0.96 1 1 1 1 0.23 0.77 1 0.48 0.52 0.98 0.98 0.98 0.98 1 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 H30

SCOTTI

Stoesser et al. 2014 Antimicrobial agents and chemotherapy

Outbreaker

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SLIDE 17

PMK4 PMK13 PMK3 PMK18 PMK26 PMK20 PMK11 PMK5 PMK19 PMK1 PMK21 PMK4 PMK21 H30 PMK15 PMK21 PMK5 PMK14 PMK13 PMK16 PMK23 PMK21 PMK6 PMK21 PMK12 PMK9 PMK22 PMK24 PMK7 PMK17 PMK26 PMK10 PMK25 NS NS PMK21 PMK5 PMK11 NS PMK21 NS NS PMK21 NS NS NS NS PMK4 NS PMK22 NS PMK13 PMK26 NS PMK4 NS NS NS PMK21 NS NS PMK21 PMK21 NS NS

[0,2]& [0,2]& [0,4]& [1,2]& [0,2]& [0,9]& [1,13]& [0,2]& [0,2]& [1,2]& [0,2]& [0,2]& [0,2]& [1,2]& [0,2]& [0,2]& [1,2]& [1,2]& [0,2]& [0,2]& [0,2]& [0,2]& [0]& [1,2]& [1,2]& [0,2]& [0]& [1,2]&

[1,2]&

  • K. Pneumoniae data

SCOTTI

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SLIDE 18

Summary SCOTTI

Different models result in different inferences. New inference of transmission in BEAST2: SCOTTI. Future work: transmission bottlenecks, introductions, epidemiological models.

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SLIDE 19

Thanks for listening!

Daniel J Wilson Chieh-Hsi Wu Crook group (NDM Microbiology)