Inference in Coupled Wright-Fisher Models [PDF]

Mar 8, 2017 - Timo Koski. Boualem Djehiche. Juma Kasozi. J. Y. T Mugisha. Main advisor. Assistant advisor. Assistant adv

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Inference in Coupled Wright-Fisher Models. Yasin Department of Mathematics, Makerere University Department of Mathematics, KTH Royal Institute of Technology First Network Meeting for Sida- and ISP-funded PhD Students in Mathematics Stockholm 7–8 March 2017

Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

My Advisors

Timo Koski Main advisor KTH

Boualem Djehiche Assistant advisor KTH

Yasin

Juma Kasozi Assistant advisor Makerere Univ.

J. Y. T Mugisha Assistant advisor Makerere Univ.

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Coupled Wright-Fisher model for two alleles and two loci

Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Outline Coupled Wright-Fisher Model

Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Outline Coupled Wright-Fisher Model Parameter Estimation

Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Outline Coupled Wright-Fisher Model Parameter Estimation Results

Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Outline Coupled Wright-Fisher Model Parameter Estimation Results Conclusion and Future work

Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Coupled Wright-Fisher Model It is a system of Stochastic differential equations of the form dXt = β11 − (β11 + β12 )Xt + θ(1 − Xt )Xt Yt +

q

dYt = β21 − (β21 + β22 )Yt + θ(1 − Yt )Yt Xt +

Xt (1 − Xt )dW1

q

Yt (1 − Yt )dW2 (1)

with initial conditions X(0) = X0 , Y (0) = Y0 and 0 ≤ Xt ≤ 1, 0 ≤ Yt ≤ 1 This is a special case of the multi locus - multiallele model by Aurell, Ekeberg, Koski (2017)

Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

the parameters are : βij assumed to be nuisance parameters θ the interaction between the two loci. Purpose: To infer the interaction from data.

Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Simulation

=0

1

=0

1 0.8

X2 0.8

X2

0.6

0.6 0.4 0.4 0.7

0.2 0.75

0.8

0.85

0.9

0.95

1

0

0.1

0.2

0.3

0.4

0.5

X

=0.02

=0.02

1

1

0.6

X

0.7

0.8

0.9

1

1

1 0.8

X2

0.95

X2

0.6

0.9 0.4 0.85 0.75

0.2 0.8

0.85

0.9

0.95

1

0

0.1

0.2

0.3

0.4

0.5

X1

X1

(a)

(b)

0.6

Yasin Figure: Simulation of coupled Wright-Fisher model for various θ.

0.7

0.8

0.9

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Simulation

=0.04

1

=0.04

1

0.9

0.95

X2 0.8

X2

0.9

0.7 0.85

0.6 0.5 0.88

0.9

0.92

0.94

0.96

0.98

1

0.8 0.75

0.8

0.85

X

X

=0.06

=0.06

1

1

0.95

1

1

0.9

0.95

1

0.98

0.98

X2

0.9 1

X2 0.96

0.96

0.94 0.94 0.92 0.9

0.92

0.91

0.92

0.93

0.94

0.95

0.96

0.97

0.98

0.99

1

0.9 0.75

0.8

0.85

X1

X1

(a)

(b)

Yasin Figure: Simulation of coupled Wright-Fisher model for various θ.

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Stationary distribution This has been found by Aurell, Ekeberg, Koski (2017). The Stationary density is P (x, y) =

1 π(x)π(y)e2θxy Z

(2)

where

Z=

π(x) =

x(2β11 −1) (1 − x)2β12 −1

π(y) =

y (2β21 −1) (1 − y)2β22 −1

∞ Γ(2(β21 + β22 )) X (2β21 )n (2θ)n Γ(2β12 ) Γ(2β11 + n) Γ(2β21 )Γ(2β22 ) n=0 (2β¯2 )n n! Γ(2β¯2 + n)

(3) Γ(z) is the Euler gamma function. Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Estimation of θ eqn(1) is of the form √ dXt = C(Xt , θ)dt +

A dW

(4)

where !

C(Xt , θ) =

!

(1 − Xt )Xt Yt β11 − (β11 + β12 )Yt (5) +θ (1 − Yt )Yt Xt β21 − (β21 + β22 )Yt

C(Xt , θ) = a(Xt ) + θg(Xt )

(6) !

A(Xt ) =

Xt (1 − Xt ) 0 0 Yt (1 − Yt )

Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Likelihood function of θ By Girsanov theorem, Z 1

n dPθ = L(θ) = exp dPθ0

1 − 2

Z 1

A−1 (C(Xt , θ) − C(Xt , θ0 )) · dXt

0

o

[A−1 C(Xt , θ) · C(Xt , θ) − A−1 C(Xt , θ0 ) · C(Xt , θ0 )]dt

(7)

0

Pθ and Pθ0 are probability measures induced by solutions of eqn(4). Particularly, θ0 = 0. A · B denotes the dot product between A and B.

Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Derivative of log-likelihood function of θ Thus, dlogL(θ) d n 1 −1 = A C(Xt , θ) · dXt dθ dθ 0 Z o 1 1 −1 − A C(Xt , θ) · C(Xt , θ)dt 2 0 Z

(8)

Subsituting for C(Xt , θ),

Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Derivative of log-likelihood function of θ Hence, dlogL(θ) dn = θ dθ dθ 1 − 2

Z 1

2

[θ A

−1

g(Xt ) · g(Xt ) + 2θA

Z 1

−1

A−1 g(Xt ) · dXt

0

o

g(Xt ) · a(Xt )]dt

(9)

0

Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

MamixumLikelihood estimate of θ For MLE, θˆ =

dlogL(θ) dθ

R1 0

=0

A−1 g(Xt ) · dXt − 01 A−1 g(Xt ) · a(Xt )dt R1 −1 0 A g(Xt ) · g(Xt )dt

Yasin

R

(10)

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

But, Z 1

A−1 g(X

−1

A

t)

=

Yt Xt

g(Xt ) · dXt =

0

!

⇒ By Ito’s formula, Z 1

Yt dXt + Xt dYt = X(1)Y (1) − X(0)Y (0)

0

The other integrals can be discretised by Classical methods for instance, Trapezoidal rule (Lucus M., 2008)

Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Simulation Results

(a)

Yasin

(b)

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Simulation Results

(e)

Yasin

(f)

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Future work In the future we intend to explore the following;

Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Future work In the future we intend to explore the following; extension our work to L loci and d alleles

Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Future work In the future we intend to explore the following; extension our work to L loci and d alleles consider a more general interaction function

Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Future work In the future we intend to explore the following; extension our work to L loci and d alleles consider a more general interaction function consider inference from real allele frequency time series data

Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Future work In the future we intend to explore the following; extension our work to L loci and d alleles consider a more general interaction function consider inference from real allele frequency time series data use bayesian inference

Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

Tack så mycket! Thank you!

Yasin

Department of Mathematics, Makerere University Department o Inference in Coupled Wright-Fisher Models.

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