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Graphical Model Representation of Pedigree Based Mixed Model - talk

Graphical Model Representation of Pedigree Based Mixed Model - talk

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Published by Gregor Gorjanc
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Gorjanc, G. 2010. Graphical Model Representation of Pedigree Based Mixed Model. 32nd ITI (http://iti.srce.hr) - Cavtat, Croatia. See paper at http://www.scribd.com/doc/27427800
Talk for

Gorjanc, G. 2010. Graphical Model Representation of Pedigree Based Mixed Model. 32nd ITI (http://iti.srce.hr) - Cavtat, Croatia. See paper at http://www.scribd.com/doc/27427800

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Published by: Gregor Gorjanc on Jun 30, 2010
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11/07/2012

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Graphical Model Representation of Pedigree Based Mixed Model

Gregor Gorjanc
University of Ljubljana, Biotechnical Faculty, Department of Animal Science, Slovenia

32nd ITI, Cavtat, Croatia 22nd June 2010

Introduction
Pedigree based mixed model = animal model y = Xb + Za + e 2 2 y|b, a, σe ∼ N Xb + Za, Iσe 2 2 a|A, σa ∼ N 0, Aσa
2 2 parameters: b, a (location) σa , σe (variance) data: y (phenotypes), A (pedigree)

Simplistic, powerful, & robust model Frequently used in:
animal and plant breeding - research & INDUSTRY evolutionary biology - research human genetics - research

Bayesian inference via McMC
Location parameters θ = (b, a)
Block-wise sampling
2 2 p θ|y, A, σa , σe 2 ∼ N θ, C−1 σe

Component-wise sampling
2 2 p θi |θ −i , y, A, σa , σe 2 ∼ N θi , C−1 σe i,i

Mixed model equations (MME)

X X X Z 2 2 ZT X ZT Z + A−1 σe/σa

T

T

Cθ = r XT y b = ZT y a

Variances . . . (see Sorensen & Gianola (2002))

Available software
Animal breeding and genetics community
DMU GIBBSF90 MCMCglmm R package MTGSAM SIR-BAYES TM VCE ...

Available software
Animal breeding and genetics community
DMU GIBBSF90 MCMCglmm R package MTGSAM SIR-BAYES TM VCE ...

General purpose statistical programs
Can we use BUGS (Bayesian Using Gibbs Sampling) program?
µ
Y1 Y2 Y3

τ
Y6

θ
Y4

Y5

Can we use BUGS for animal model? YES!
Previous work
Damgaard (2007) Technical note: How to use Winbugs to draw inferences in animal models. J. Anim. Sci., 85(6): 1363-1368. http://jas.fass.org/cgi/reprint/85/6/1363.pdf Waldmann (2009) Easy and flexible Bayesian inference of quantitative genetic parameters. Evolution, 63(6): 1640-1643. http://www3.interscience.wiley.com/ journal/121675188/abstract

Aim of my work Fit animal model in BUGS in a general manner

How?
Describe animal model as a graphical model using Directed Acyclic Graph (DAG)

µ
Y1 Y2 Y3

τ
Y6

p (z) =
zi ∈z

p zi |zparents(i)

θ
Y4

Y5

p (zi |z−i ) ∝ p zi |zparents(i) × p zj |zparents(j)
zj ∈zchildren(i)

DAG for the “alien” example

Figure by Jouke

DAG for the “alien” example
2 σa 2 σe

a1 98 a3 a5 a7

a2 a4 a6 a8 109 a10 a9

Figure by Jouke

DAG for the “alien” example
2 σa 2 σe

103 a1 98 a3 a5 a7 106 a2 a4 106 a8 109
Figure by Jouke

101 a6 93 a9 a10

DAG for the “alien” example
2 σa 2 σe

b1 103 a1 98 a3 a5 a7 106 a2 a4 106 a8 109
Figure by Jouke

b2

101 a6 93 a9 a10

DAG for the “alien” example
2 σa 2 σe

b1 103 a1 98 a3 a5 a7 106 a2 a4 106 a8 109
Figure by Jouke

b2

101 a6 93 a9 a10

Equivalence between DAG and MME
XT X XT Z 2 2 ZT X ZT Z + A−1 σe/σa b a = XT y ZT y a σ2
b1 103
−1

2 σe

b2 a1 106 a2 a4 a5 a7 106 a8 109 a10 101 a6 93 a9

A = TWT = (I − 1/2P)−1 W I − 1/2PT A−1 = T−1
T

T

W−1 T−1 −
1/2P)

98

a3

= (I −

1/2P)T W−1 (I

Component-wise sampling
b1 b2 y21 a1 y3 a3 a5 a7 y22 a2 a4 y5 a8 y10 a10 a6 y4 y6 a9

p (zi |z−i ) ∝ p zi |zparents(i) × p zj |zparents(j)
zj ∈zchildren(i)

Markov blanket (for a5 )
“parents” (a3 , a4 ) “children” (y5 , a7 , a8 ) “mates” (b2 , a6 )

DAG description with BUGS model language
## Phenotypic values y21 ∼ dnorm(mu21, tau2e) mu21 <- b2 + a2 ## Additive genotypic values a1 ∼ dnorm(0, tau2a) ... a4 ∼ dnorm(pa4, tau2a4) pa4 <- 0.5 * (a2 + 0); tau2a4 <- winv4 * tau2a ... a10 ∼ dnorm(pa10, tau2a10) pa10 <- 0.5 * (a8 + a9); tau2a10 <- winv10 * tau2a ## Other priors b2 ∼ dnorm(0, 100) ...

Heritability for the "alien” example - prior effect1
Non-informative prior tau2e ∼ dgamma(1, 1) tau2a ∼ dgamma(1, 1) Informative prior tau2e ∼ dgamma(5, 120) tau2a ∼ dgamma(15, 240)

0.0 0.2 0.4 0.6 0.8 1.0
1

0.0 0.2 0.4 0.6 0.8 1.0

For details see Sorensen & Gianola (2002) - Example 2.21 (p. 109-111)

Conclusions
Pedigree based mixed model (animal model) can be represented as a graphical model - this provides a way to use standard graphical model software

Any questions?

Figure by Jouke

Abstract

Pedigree based mixed model represents a simplistic yet robust and powerful model frequently used in animal and plant breeding, evolutionary biology, and human genetics. In the Bayesian setting inference of all model parameters can be performed with the use of well known McMC methods. Algorithms are commonly formulated with matrices, which provides a generic view, but hinders interpretation. Here, a generic graphical model representation is developed. This eases the interpretation of the model and used algorithms. In addition, graphical model formulation provides a way to fit pedigree based mixed model in standard graphical model programs, such as BUGS.

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