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Randomized Quantile Residual for Assessing GeneralizedLinear Mixed Models with Application to Zero-inflated
Microbiome Data
Longhai Li
Department of Mathematics and StatisticsUniversity of SaskatchewanSaskatoon, SK, CANADA
5 June 2018Annual Meeting of Statistical Society of Canada
McGill University, Montreal, Canada
Acknowledgements
This talk is based on the results of the M.Sc thesis project undertakenby Wei Bai, co-supervised with Cindy X. Feng (U of S).
Thank Prof. Wei Xu (U of T) for providing the microbiome data forthis research.
Thank NSERC and CFI for providing grants for my research.
Thank the ICSA Canada Chapter, particularly Prof. Changbao Wu(U of Waterloo), for organizing and sponsoring this session.
Outline
1 Introduction
2 Zero-inflated/modified Generalized Linear Mixed Models
3 Randomized Quantile Residual
4 Simulation StudiesDescription of Data Generating ProcessAssessing Models for Datasets Simulated from ZMP ModelAssessing Models for Datasets Simulated from ZMNB Model
5 Application to a Twin Study OTU Dataset
6 Conclusions and Discussions
Section 1
Introduction
Introduction
The operational taxonomic unit (OTU) counts in microbiome datasetshave characteristics of zero-inflation and over-dispersion. Variousgeneralized mixed models have been proposed to to fit the data.
Correctness in model specification plays extremely important role instatistical inference, for example in calculating p-values/q-values forselecting OTUs that are related to a phenotype.
Pearson and deviance residuals are often used in practice withoutjustification. However, when applied to count data, the distributionsof these residuals are far from the normal distribution.
Randomized quantile residual (RQR) was originally proposed by Dunnand Smyth (1996) as an alternative for Pearson and devianceresiduals. However, it has NOT been used much by statisticians.
We investigate the performance of RQR in checkingzero-inflated/modified generalized linear mixed effect (GLMM)models using simulated and real datasets.
1. Introduction/ 1/39
Section 2
Zero-inflated/modified Generalized Linear MixedModels
Generalized Linear Mixed Model
As an example of GLMM, NB mixed model (NB) is described as follows:
A probability distribution for the response (yi ) given a mean functionµi and other parameters, eg.
yi |µi ∼ Negative-Binomial(µi , k)
A link function for linking the mean µi to a linear function of fixedfactor (Xi ) and random factors (Zi ), eg.
log(µi ) = Xiβ + Ziu
Certain penalization (often normal) is imposed to u.
2. Zero-inflated/modified Generalized Linear Mixed Models/ 2/39
Zero-inflated Poisson (ZIP) Model: I
The zero-inflated Poisson with parameters λi and pi , denoted byZIP(λi , pi ), is defined as:
yi ∼
{0, with probability pi
Poisson(µi ), with probability 1− pi .(1)
The following link functions are often used:
log(µi ) = offseti + Xiβ + Ziu (2)
log
(pi
1− pi
)= offseti + Xi β + Zi u, (3)
2. Zero-inflated/modified Generalized Linear Mixed Models/ 3/39
Zero-inflated Poisson (ZIP) Model: II
The PMF and CDF of the ZIP distribution:
dzip(yi = 0) = pi + (1− pi )× e−µi (4)
dzip(yi = j) = (1− pi )e−µiµji
j!, for j > 0 (5)
pzip(yi = J;µi , pi ) = pi + (1− pi )ppois(J, µi ). (6)
The mean and variance of a ZIP random variable can be calculated by
E (yi ) = (1− pi )× µi (7)
V (yi ) = (1− pi )×(µi + pi × µi 2
). (8)
2. Zero-inflated/modified Generalized Linear Mixed Models/ 4/39
Zero-inflated Negative-Binomial (ZINB) Model: I
Zero-inflated NB(ZINB) can be defined similarly as ZIP, with Poissonreplaced by NB.
The PMF and CDF of the ZINB distribution:
dzinb(yi = 0) = pi + (1− pi )×(
k
k + µi
)k
(9)
dzinb(yi = j) = (1− pi )× dnb(j , µi , k), for j > 0 (10)
pzinb(yi ;µi , k , pi ) = pi + (1− pi )pnb(yi , µi , k) (11)
The mean and variance of a ZIP random variable can be calculated by
E (yi ) = (1− pi )× µi (12)
V (yi ) = (1− pi )×(µi +
µi2
k
)+ µi
2 ×(pi
2 + pi)
(13)
2. Zero-inflated/modified Generalized Linear Mixed Models/ 5/39
Zero-modified Poisson (ZMP): I
Zero-Modified Model: Zero-modified models are also called hurdle models.A logistic regression for the zero indicator (Zi ):
Pr(Zi = z) =
{πi , z = 0
1− πi , z = 1.(14)
Given Zi , the conditional probability mass function for Yi is:Pr(Yi = yi |Zi = 0) = I (yi = 0)
Pr(Yi = yi |Zi = 1) = dpois(yi )
1−dpois(0)I (yi > 0).
(15)
The unconditional probability mass function for Yi is
Pr(Yi = yi ) =
πi , if yi = 0
(1− πi ) dpois(yi )
1−dpois(0), if yi > 0.
(16)
2. Zero-inflated/modified Generalized Linear Mixed Models/ 6/39
Zero-modified Poisson (ZMP): II
We often used the log link functions for non-zero count mean µi and logisticlink for πi :
log(µi ) = offseti + Xiβ + Ziu (17)
log
(πi
1− πi
)= offseti + Xi β + Zi u, (18)
The PMF and CDF of ZMP distribution:
dzmp(yi = 0) = πi (19)
dzmp(yi = j) = (1− πi )dpois(j)
1− ppois(0), for j > 0 (20)
pzmp(yi ;µi , πi ) = πi + (1− πi )ppois(yi ;µi , πi )− ppois(0)
1− ppois(0), (21)
2. Zero-inflated/modified Generalized Linear Mixed Models/ 7/39
Zero-modified NB (ZMNB)
ZMNB model can be defined analogously. The PMF and CDF of ZMNBdistribution:
dzmnb(yi = j) = πi I (j = 0) + (1− πi )dnb(yi )
1− pnb(0)I (j > 0) (22)
pzmnb(yi ;µi , k, πi ) = πi + (1− πi )pnb(yi )− pnb(0)
1− pnb(0). (23)
The same link functions as in ZMP are used for ZMNB.
The mean and variance of ZMNB:
E (yi ) =1− πi1− p0
× µi (24)
V (yi ) =1− πi1− p0
×(µi + µ2
i +µi
2
k
)−(
1− πi1− p0
× µi
)2
. (25)
2. Zero-inflated/modified Generalized Linear Mixed Models/ 8/39
Section 3
Randomized Quantile Residual
Problems with Pearson and Deviance Residuals
In regression models for discrete outcomes, the residuals are far fromnormality, with residuals clustering on lines according to distinctresponse values, which poses great challenges for visual inspection.Therefore, residual plots for the diagnosis of models for discreteoutcome variables give very limited meaningful information for modeldiagnosis.
The Pearson χ2 statistic is written as, X 2 =∑n
i=1 r2i , and the
deviance (χ2 statistic) is written as, D =∑n
i=1 d2i . The asymptotic
distribution of D and X 2 under the true model is often assumed to beχ2n−p. However, the use of this asymptotic distribution for both X 2
and D is lack of theoretical underpinning.
3. Randomized Quantile Residual/ 9/39
A First Look at Three Residuals
Pearson
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−1.5 −0.5 0.0 0.5 1.0 1.5
−1
01
23
45
x
Pea
rson
Deviance
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−1.5 −0.5 0.0 0.5 1.0 1.5−
2−
10
12
3
x
Dev
ianc
e
Randomized Quantile
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−1.5 −0.5 0.0 0.5 1.0 1.5
−3
−2
−1
01
23
x
Ran
dom
ized
Qua
ntile
A simulated dataset is checked against the true generating model.However, Pearson and deviance residuals exhibit trend and cluster inlines.
In addition, the often used χ2 tests are not well-calibrated.
3. Randomized Quantile Residual/ 10/39
Definition of Randomized Quantile Residual
Predictive p-value for continuous yi :
F (yi ; µi , φ) = P(Yi ≤ yi | µi , φ)
Randomized predictive p-valueIf F is discrete, the estimated lower tail probability is randomized intoa uniform random number.
F ∗(yi ; µi , φ, ui ) = F (yi−; µi , φ) + ui P(yi ; µi , φ), (26)
where ui from uniform distribution on (0, 1], F (yi−; µi , φ) is the lowerlimit of F at yi , i.e., supy<yi F (y ; µi , φ), the lower limit in the “gap”
of F (·, µi , φ) at yi .Randomized quantile residual
qi = Φ−1(F ∗(yi ; µi , φ, ui )) (27)
where Φ−1 is the quantile function of a standard normal distribution
3. Randomized Quantile Residual/ 11/39
An Illustrative Example for RQR: I
The true model:We simulate a response variable of size n = 1000 from a Poissonmodel with
log(µi ) = −1 + 2sin(2xi ),
where µi is the expected mean count for the ith subject andxi ∼ Uniform(0, 2π), i = 1, · · · , nA wrong model:Poisson model with mean structure
log(µi ) = β0 + β1xi
with xi as a predictor with linear effect.
3. Randomized Quantile Residual/ 12/39
An Illustrative Example for RQR: II
0 1 2 3 4 5 6
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F*
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● ● ● ● ● ● ● ●0 1 2 3 4 5 6 7
3. Randomized Quantile Residual/ 13/39
Normality of Randomized Quantile Residual (RQR)
Theorem
Suppose a continuous random variable Y has the CDF F (y), then F (Y ) isuniformly distributed on (0,1].
Theorem
Suppose the true distribution of Yi given Xi has the CDF F (yi ;µi , φ) andPMF P(yI ;µi , φ), where µi is a function of Xi involving the modelparameters. The randomized lower tail probability F ∗(yi ;µi , φ, ui ) isdefined as F (yi−;µi , φ) + ui P(yI ;µi , φ) (26). Suppose Ui is uniformlydistributed on (0,1]. Then, we have
F ∗(Yi ;µi , φ,Ui ) ∼ Uniform((0, 1]), (28)
andqi = φ−1(F ∗(Yi ;µi , φ,Ui )) ∼ N(0, 1). (29)
3. Randomized Quantile Residual/ 14/39
Proof of Normality of RQR
For any interval B ⊆ (0, 1],
P(F ∗(Yi ;µi , φ,Ui ) ∈ B|Yi = k(j)) =length(F (j) ∩ B)
p(j),
where length(·) is the length of interval. By the law of total probability,
P(F ∗(Yi ;µi , φ,Ui ) ∈ B) (30)
=∞∑j=1
P(F ∗(Yi ;µi , φ,Ui ) ∈ B|Yi = k(j))× P(Yi = k(j)) (31)
=∞∑j=1
length(F (j) ∩ B)
p(j)× p(j) (32)
=∞∑j=1
length(F (j) ∩ B) (33)
= length(∪∞j=1F(j) ∩ B) = length(B) (34)
3. Randomized Quantile Residual/ 15/39
Section 4
Simulation Studies
Subsection 1
Description of Data Generating Process
General Form of Microbiome Dataset
OTU1 ... OTUm Total Reads Host Factors Sample VariablesY1 Ym Offset Fixed Factors Random Factors
sample 1 Y11 ... Y1m T1 X11 ... X1s Z11 ... Z1t
. . ... . . ... ...
. . ... . . ... ...
. . ... . . ... ...sample n Yn1 ... Ynm Tn Xn1 ... Xns Zn1 ... Znt
4. Simulation Studies/Description of Data Generating Process 16/39
Link Functions and Parameters in Data Generation
Link Functions
log(µi ) = log(Ti ) + β0 + β(1)Xi1
+ ...+ β(s)Xis
+ u(1)Zi1
+ ...+ u(t)Zit,
log(πi
1− πi) = β0 + β
(1)Xi1
+ ...+ β(s)Xis
+ u(1)Zi1
+ ...+ u(t)Zit
Parameters:
Parameter Generator
β0 -0.2
β, β N(0, 0.12)u, u N(0, 22)k (ZMNB) Unif(1,2)Ti Poisson(3× 105)
Other Settings: m = 3000, s = 3, t = 3; each fixed factor has 5 levelsand each random factor has 10 levels.
4. Simulation Studies/Description of Data Generating Process 17/39
Steps to Generate OTUs with ZMP/ZMNB Model
Step 1: Generate matrix of fixed and random factors, and total reads Ti
randomly (used for all Yj).For each response Yj :Step 2: Compute πij and µij using link functions with randomly generatedparameters.Step 3: We generate a count indicator Zij as a binary Bernoulli randomvariable:
Zij =
{0, with probability πij
1 with probability 1− πij .(35)
Step 4: If the indicator Zij = 0, then Yij = 0. If the indicator Zij = 1,then Yij follows a truncated Poisson or NB model, e.g.,
Yij ∼ Truncated-Poisson(µij).
4. Simulation Studies/Description of Data Generating Process 18/39
Subsection 2
Assessing Models for Datasets Simulated from ZMP Model
Checking One Yj : RQR plot vs Fitted Values
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400000 600000 800000 1000000 1400000
−3−2
−10
12
Fitted values
Rand
omize
d Qu
antile
ZMP
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400000 600000 800000 1000000 1400000
−2−1
01
2
Fitted values
Rand
omize
d Qu
antile
ZIP
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400000 600000 800000 1000000 1400000
−3−2
−10
12
Fitted values
Rand
omize
d Qu
antile
ZMNB
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−6−4
−20
24
6
Fitted values
Rand
omize
d Qu
antile
Poisson
4. Simulation Studies/Assessing Models for Datasets Simulated from ZMP Model 19/39
Checking One Yj : QQ-plot of RQR
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−3 −2 −1 0 1 2 3
−3−2
−10
12
Randomized Quantile
Theoretical Quantiles
Sam
ple Q
uant
iles
ZMP
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−3 −2 −1 0 1 2 3
−2−1
01
2
Randomized Quantile
Theoretical Quantiles
Sam
ple Q
uant
iles
ZIP
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−3 −2 −1 0 1 2 3
−3−2
−10
12
Randomized Quantile
Theoretical Quantiles
Sam
ple Q
uant
iles
ZMNB
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−3 −2 −1 0 1 2 3
−6−4
−20
24
6
Randomized Quantile
Theoretical Quantiles
Sam
ple Q
uant
iles
Poisson
4. Simulation Studies/Assessing Models for Datasets Simulated from ZMP Model 20/39
Checking One Yj : Pearson Residual vs Fitted Values
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400000 600000 800000 1000000 1400000
−6−4
−20
2
Fitted values
Pear
son
ZMP
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400000 600000 800000 1000000 1400000
−6−4
−20
2
Fitted values
Pear
son
ZIP
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400000 600000 800000 1000000 1400000
−6−4
−20
2
Fitted values
Pear
son
ZMNB
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2e+05 5e+05 1e+06 2e+06
−100
0−5
000
500
1000
Fitted values
Pear
son
Poisson
4. Simulation Studies/Assessing Models for Datasets Simulated from ZMP Model 21/39
Checking One Yj : QQ-plot of Pearson Res.
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−3 −2 −1 0 1 2 3
−6−4
−20
2
Pearson
Theoretical Quantiles
Sam
ple Q
uant
iles
ZMP
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−3 −2 −1 0 1 2 3
−6−4
−20
2
Pearson
Theoretical Quantiles
Sam
ple Q
uant
iles
ZIP
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−3 −2 −1 0 1 2 3
−6−4
−20
2
Pearson
Theoretical Quantiles
Sam
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ZMNB
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−3 −2 −1 0 1 2 3
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000
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1000
Pearson
Theoretical Quantiles
Sam
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Poisson
4. Simulation Studies/Assessing Models for Datasets Simulated from ZMP Model 22/39
Checking All Yj ’s: 3000 Shapiro-Wilk P-values of RQRRandomized Quantile
p−value
Frequency
0.0 0.2 0.4 0.6 0.8 1.0
050
100
150
200
250
300
ZMP
Randomized Quantile
p−value
Frequency
0.0 0.2 0.4 0.6 0.8 1.0
050
100
150
200
250
300
ZIPRandomized Quantile
p−value
Frequency
0.0 0.2 0.4 0.6 0.8 1.0
050
100
150
200
250
300
ZMNB
Randomized Quantile
p−value
Frequency
0e+00 1e−18 2e−18 3e−18 4e−18 5e−18 6e−18
0500
1000
1500
2000
2500
3000
Poisson
4. Simulation Studies/Assessing Models for Datasets Simulated from ZMP Model 23/39
Checking All Yj ’s: 3000 Shapiro-Wilk P-values of PearsonPearson
p−value
Frequency
0.0e+00 2.0e−47 4.0e−47 6.0e−47 8.0e−47 1.0e−46 1.2e−46
0500
1000
1500
2000
2500
3000
ZMP
Pearson
p−value
Frequency
0.0e+00 5.0e−06 1.0e−05 1.5e−05 2.0e−05 2.5e−05
0500
1000
1500
2000
2500
3000
ZIPPearson
p−value
Frequency
0.0e+00 2.0e−47 4.0e−47 6.0e−47 8.0e−47 1.0e−46 1.2e−46
0500
1000
1500
2000
2500
3000
ZMNB
Pearson
p−value
Frequency
0.0e+00 5.0e−06 1.0e−05 1.5e−05 2.0e−05 2.5e−05
0500
1000
1500
2000
2500
3000
Poisson
4. Simulation Studies/Assessing Models for Datasets Simulated from ZMP Model 24/39
Type 1 Error Rates and Power
Using 0.05 as cutoff, probabilities of rejecting fitted models with RQRs andPearson residuals in 3000 Yj ’s are shown as follows:
Table 1: Using Randomized Quantile Residual
Sample size ZMP ZIP ZMNB Poisson200 0.142 0.139 0.145 1.000400 0.074 0.090 0.102 0.999800 0.068 0.068 0.082 1.000
1600 0.060 0.061 0.059 1.0003200 0.051 0.051 0.063 1.000
Table 2: Using Pearson Residual
Sample size ZMP ZIP ZMNB Poisson200 0.984 0.986 0.983 0.997400 1.000 1.000 1.000 1.000800 1.000 1.000 1.000 1.000
1600 1.000 1.000 1.000 1.0003200 1.000 1.000 1.000 1.000
4. Simulation Studies/Assessing Models for Datasets Simulated from ZMP Model 25/39
Subsection 3
Assessing Models for Datasets Simulated from ZMNB Model
Checking One Yj : RQR vs Fitted Values
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−3−2
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ZMNB
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600000 800000 1000000 1200000 1600000
−3−2
−10
12
34
Fitted values
Rand
omize
d Qu
antile
ZINB
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1e+03 1e+04 1e+05 1e+06 1e+07
−3−2
−10
12
Fitted values
Rand
omize
d Qu
antile
NB
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5e+05 1e+06 2e+06
−4−2
02
46
Fitted values
Rand
omize
d Qu
antile
ZMP
4. Simulation Studies/Assessing Models for Datasets Simulated from ZMNB Model 26/39
Checking One Yj : QQ plot of RQR
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−3 −2 −1 0 1 2 3
−3−2
−10
12
34
Randomized Quantile
Theoretical Quantiles
Sam
ple Q
uant
iles
ZMNB
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−3 −2 −1 0 1 2 3
−3−2
−10
12
34
Randomized Quantile
Theoretical Quantiles
Sam
ple Q
uant
iles
ZINB
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−3 −2 −1 0 1 2 3
−3−2
−10
12
Randomized Quantile
Theoretical Quantiles
Sam
ple Q
uant
iles
NB
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−3 −2 −1 0 1 2 3
−4−2
02
46
Randomized Quantile
Theoretical Quantiles
Sam
ple Q
uant
iles
ZMP
4. Simulation Studies/Assessing Models for Datasets Simulated from ZMNB Model 27/39
Checking One Yj : Pearson Residuals vs Fitted Values
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600000 800000 1000000 1200000 1600000
02
46
8
Fitted values
Pear
son
ZMNB
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600000 800000 1000000 1200000 1600000
−0.5
0.0
0.5
1.0
1.5
2.0
2.5
Fitted values
Pear
son
ZINB
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1e+03 1e+04 1e+05 1e+06 1e+07
01
23
Fitted values
Pear
son
NB
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5e+05 1e+06 2e+06
−500
050
010
0015
0020
00
Fitted values
Pear
son
ZMP
4. Simulation Studies/Assessing Models for Datasets Simulated from ZMNB Model 28/39
Checking One Yj : QQ plot of Pearson Residuals
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−3 −2 −1 0 1 2 3
02
46
8
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Sam
ple Q
uant
iles
ZMNB
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−3 −2 −1 0 1 2 3
−0.5
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2.5
Pearson
Theoretical Quantiles
Sam
ple Q
uant
iles
ZINB
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−3 −2 −1 0 1 2 3
01
23
Pearson
Theoretical Quantiles
Sam
ple Q
uant
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NB
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−3 −2 −1 0 1 2 3
−500
050
010
0015
0020
00
Pearson
Theoretical Quantiles
Sam
ple Q
uant
iles
ZMP
4. Simulation Studies/Assessing Models for Datasets Simulated from ZMNB Model 29/39
Checking All Yj ’s: 3000 Shapiro-Wilk P-values of of RQRRandomized Quantile
p−value
Frequency
0.0 0.2 0.4 0.6 0.8 1.0
050
100
150
200
250
300
ZMNB
Randomized Quantile
p−value
Frequency
0.0 0.2 0.4 0.6 0.8 1.0
050
100
150
200
250
300
350
ZINBRandomized Quantile
p−value
Frequency
0.000 0.005 0.010 0.015 0.020
0500
1000
1500
2000
2500
3000
NB
Randomized Quantile
p−value
Frequency
0.0e+00 5.0e−48 1.0e−47 1.5e−47
0500
1000
1500
2000
2500
3000
ZMP
4. Simulation Studies/Assessing Models for Datasets Simulated from ZMNB Model 30/39
Checking All Yj ’s: 3000 Shapiro-Wilk P-values of PearsonPearson
p−value
Frequency
0e+00 2e−43 4e−43 6e−43
0500
1000
1500
2000
2500
3000
ZMNB
Pearson
p−value
Frequency
0.0e+00 5.0e−58 1.0e−57 1.5e−57 2.0e−57 2.5e−57 3.0e−57
0500
1000
1500
2000
2500
3000
ZINBPearson
p−value
Frequency
0e+00 1e−05 2e−05 3e−05 4e−05 5e−05 6e−05
0500
1000
1500
2000
2500
3000
NB
Pearson
p−value
Frequency
0.0e+00 5.0e−60 1.0e−59 1.5e−59 2.0e−59
0500
1000
1500
2000
2500
3000
ZMP
4. Simulation Studies/Assessing Models for Datasets Simulated from ZMNB Model 31/39
Type 1 Error Rates and Power
Using 0.05 as cutoff, probabilities of rejecting fitted models with RQRs andPearson residuals in 3000 Yj ’s are shown as follows:
Table 3: Using Randomized Quantile Residuals
Sample size ZMNB ZINB NB ZMP200 0.067 0.153 0.957 1.000400 0.057 0.063 0.883 1.000800 0.053 0.049 0.759 1.000
1600 0.047 0.055 0.928 1.0003200 0.040 0.042 1.000 1.000
Table 4: Using Pearson Residuals
Sample size ZMNB ZINB NB ZMP200 1.000 1.000 1.000 1.000400 1.000 1.000 1.000 1.000800 1.000 1.000 1.000 1.000
1600 1.000 1.000 1.000 1.0003200 1.000 1.000 1.000 1.000
4. Simulation Studies/Assessing Models for Datasets Simulated from ZMNB Model 32/39
Section 5
Application to a Twin Study OTU Dataset
Data Description
We use a twin study OTU data at the genus level. There are m = 14different genera (14 Yj) on n = 287 samples in total.
We apply six different models proposed before to fit into this twinstudy OTU data and use randomized quantile residuals to test thegoodness of fit for all OTUs.
We choose ancestry and obesity to be host factors while age andfamily to be random factors.
At the genus level, the dataset does not have many zero. However,the ordinary NB and Possion models do not fit the dataset well (to beshown).
We combine small OTU counts smaller than 10 into a bin called“zero” for 10 genera, and using larger thresholds (less than 150) forother 4 genera.
5. Application to a Twin Study OTU Dataset/ 33/39
Histograms of OTUs of 4 GeneraOTU
value
Freq
uenc
y
0 1000 2000 3000 4000 5000 6000
020
4060
80
Bacteroides
OTU
value
Freq
uenc
y
0 1000 2000 3000 4000
050
100
150
Lachnospiraceae..gOTU
value
Freq
uenc
y
0 500 1000 1500 2000 2500
020
4060
8010
012
014
0
Roseburia
OTU
value
Freq
uenc
y
0 500 1000 1500 2000 2500 3000
010
2030
4050
60
Faecalibacterium
5. Application to a Twin Study OTU Dataset/ 34/39
Histograms of Randomized Predictive P-values for “Euba”pvaluepoisson
p−value
Frequency
0.0 0.2 0.4 0.6 0.8 1.0
020
4060
80100
120
Poisson1
pvaluenb
p−value
Frequency
0.0 0.2 0.4 0.6 0.8 1.0
010
2030
40
NB1
pvaluepoisson
p−value
Frequency
0.0 0.2 0.4 0.6 0.8 1.0
020
4060
80100
Poisson
pvaluenb
p−value
Frequency
0.0 0.2 0.4 0.6 0.8 1.0
010
2030
4050
NBpvalueZIP
p−value
Frequency
0.0 0.2 0.4 0.6 0.8 1.0
010
2030
4050
60
ZIP
pvaluehurdlep
p−value
Freq
uenc
y
0.0 0.2 0.4 0.6 0.8 1.0
010
2030
4050
ZMP
pvaluehurdlenb
p−value
Frequency
0.0 0.2 0.4 0.6 0.8 1.0
05
1015
2025
3035
ZMNB
pvalueZINB
p−value
Frequency
0.0 0.2 0.4 0.6 0.8 1.0
05
1015
2025
3035
ZINB
5. Application to a Twin Study OTU Dataset/ 35/39
RQR vs Fitted Values for “Euba”
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5e−02 5e−01 5e+00 5e+01
−6−4
−20
24
6
Fitted values
Ran
dom
ized
Qua
ntile
Poisson1
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1e−02 1e−01 1e+00 1e+01 1e+02
−3−2
−10
12
Fitted values
Ran
dom
ized
Qua
ntile
NB1
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5e−02 5e−01 5e+00 5e+01
−6−4
−20
24
6
Fitted values
Ran
dom
ized
Qua
ntile
Poisson
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1e−02 1e−01 1e+00 1e+01 1e+02
−3−2
−10
12
Fitted values
Ran
dom
ized
Qua
ntile
NB
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5e−02 5e−01 5e+00 5e+01
−20
24
6
Fitted values
Ran
dom
ized
Qua
ntile
ZIP
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5e−02 5e−01 5e+00 5e+01
−20
24
6
Fitted values
Ran
dom
ized
Qua
ntile
ZMP
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5e−02 5e−01 5e+00 5e+01
−2−1
01
2
Fitted values
Ran
dom
ized
Qua
ntile
ZINB
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5e−02 5e−01 5e+00 5e+01
−3−2
−10
12
Fitted values
Ran
dom
ized
Qua
ntile
ZMNB
5. Application to a Twin Study OTU Dataset/ 36/39
QQ-plot of RQR for “Euba”
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−3 −2 −1 0 1 2 3
−6−4
−20
24
6
rqrpoisson
Theoretical Quantiles
Sam
ple
Qua
ntile
s
Poisson1
●
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−3 −2 −1 0 1 2 3
−3−2
−10
12
rqrnb
Theoretical Quantiles
Sam
ple
Qua
ntile
s
NB1
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−3 −2 −1 0 1 2 3
−6−4
−20
24
6
rqrpoisson
Theoretical Quantiles
Sam
ple
Qua
ntile
s
Poisson
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−3 −2 −1 0 1 2 3
−3−2
−10
12
rqrnb
Theoretical Quantiles
Sam
ple
Qua
ntile
s
NB
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−3 −2 −1 0 1 2 3
−20
24
6
rqrZIP
Theoretical Quantiles
Sam
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Qua
ntile
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−3 −2 −1 0 1 2 3
−20
24
6
rqrhurdlep
Theoretical Quantiles
Sam
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Qua
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−3−2
−10
12
rqrZINB
Theoretical Quantiles
Sam
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Qua
ntile
s
ZINB
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−3 −2 −1 0 1 2 3
−3−2
−10
12
rqrhurdlenb
Theoretical Quantiles
Sam
ple
Qua
ntile
s
ZMNB
5. Application to a Twin Study OTU Dataset/ 37/39
Shapiro-Wilk P-values for all 14 Genera
Table 5: P-values for the Shapiro-Wilk test of Randomized quantile residuals fortwin study OTU data sorted by ZMNB
Genus ZMNB ZINB ZMP ZIP NB Poisson NB1 Poisson1
Bact 0.052 0.034 < 10−19 < 10−19 < 10−16 < 10−18 < 10−8 < 10−17
Lach..g 0.072 0.074 < 10−16 < 10−15 < 10−3 < 10−11 0.005 < 10−4
Faec 0.083 0.107 < 10−17 < 10−18 < 10−17 < 10−15 < 10−10 < 10−13
Rumi 0.232 0.285 < 10−19 < 10−19 < 10−6 < 10−12 0.04 < 10−5
Rumi.1 0.238 0.366 < 10−16 < 10−16 < 10−10 < 10−11 < 10−5 < 10−10
Blau 0.251 0.104 < 10−10 < 10−10 0.087 < 10−12 0.182 < 10−12
Erys 0.344 0.258 < 10−16 < 10−17 < 10−4 < 10−7 0.314 < 10−5
Alis 0.344 0.352 < 10−16 < 10−16 < 10−9 < 10−7 0.003 < 10−6
Euba 0.461 0.539 < 10−15 < 10−15 < 10−10 < 10−6 0.006 < 10−4
Lach 0.521 0.358 < 10−9 < 10−10 < 10−10 < 10−5 0.003 0.051Oscil 0.535 0.606 < 10−15 < 10−15 < 10−9 < 10−5 0.006 < 10−4
Prev 0.605 0.269 < 10−17 < 10−17 < 10−4 < 10−12 0.002 < 10−12
Rose 0.627 0.613 < 10−13 < 10−14 < 10−6 < 10−13 0.749 < 10−13
Copr 0.752 0.721 < 10−13 < 10−14 < 10−8 < 10−6 0.245 < 10−6
5. Application to a Twin Study OTU Dataset/ 38/39
Conclusions and Discussions
Our studies show that RQR performs very well for checking GLMM.RQRs are normally distributed under the true model. In GOF test, thetype 1 error rates of RQR are close to the nominal level 0.05, and thestatistical powers of RQR in rejecting wrong models are very good.
We have applied RQR to assess models for a real human microbiomedataset at genus level and found that ZMNB and ZINB are goodmodels for the dataset and other simpler models (such as NB andPoisson) are not adequate to describe the extraordinarily small andlarge OTU counts.
We have developed generic functions for computing RQRs with fittingoutputs of R package glmmTMB. They will be released in Wei Bai’sM.Sc. thesis.
6. Conclusions and Discussions/ 39/39