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NLME_Analysis_Diagnostic Plots.Rmd
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NLME_Analysis_Diagnostic Plots.Rmd
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---
title: "**THE UTILITY OF MIXED-EFFECT MODELS IN THE EVALUATION OF COMPLEX GENOMIC TRAITS IN-VITRO**"
author:
- Nathan Alade, M.S.^[University of Washington, Department of Pharmaceutics]
- Abhinav Nath, Ph.D.^[University of Washington, Department of Medicinal Chemistry]
- Nina Isoherannen, Ph.D.*
- Kenneth Thummel, Ph.D.*
date: "Last compiled on: `r format(Sys.time(), '%B %d, %Y')`"
output:
bookdown::pdf_document2:
toc: yes
number_sections: no
highlight: kate
citation_package: natbib
latex_engine: xelatex
bookdown: default
subtitle: |
| **Supplementary Data:** Diagnostic Plots
| (with Code)
bibliography: packages.bib
csl: American_Chemical_Society.csl
include-before:
- '`\newpage{}`{=latex}'
---
```{r setup, include=FALSE}
knitr::opts_chunk$set(echo = TRUE)
# Load Workspace
load("R Output/NLME_Analysis.RData")
```
\newpage
# **Correspondence**
**Corresponding Author:** Nathan Alade, M.S.
**Address:**
- University of Washington School of Pharmacy
- Department of Pharmaceutics
- H-272 Health Sciences Building, Box 357610
- Seattle, Washington 98195
**Email:** [alade\@uw.edu](mailto:alade@uw.edu){.email}
**Phone:** 206-543-9434
**Fax:** 206-543-3204
### **Data Availability:**
R Scripts and data necessary to reproduce our analysis are available and can be cloned using the following public repository. (<http://nathanalade.github.io/In-Vitro-NLME/>)
\newpage
# **Final Model Residual Plots (UM/EM)**
## **Rich Study Designs (0-20% CV)**
```{r fig.show="hold", out.width="50%"}
par(mfrow = c(1, 2))
plot(rich_covar.nlme, main = "UM/EM Rich (0% CV)")
plot(rich_CV5_covar.nlme, main = "UM/EM Rich (5% CV)")
plot(rich_CV10_covar.nlme, main = "UM/EM Rich (10% CV)")
plot(rich_CV20_covar.nlme, main = "UM/EM Rich (20% CV)")
```
\newpage
## **Sparse Study Designs (3pt, 0-20% CV)**
```{r fig.show="hold", out.width="50%"}
par(mfrow = c(1, 2))
plot(sparse3pt_covar.nlme, main = "UM/EM Sparse (3pt, 0% CV)")
plot(sparse3pt_CV5_covar.nlme, main = "UM/EM Sparse (3pt, 5% CV)")
plot(sparse3pt_CV10_covar.nlme, main = "UM/EM Sparse (3pt, 10% CV)")
plot(sparse3pt_CV20_covar.nlme, main = "UM/EM Sparse (3pt, 20% CV)")
```
\newpage
## **Sparse Study Designs (4pt, 0-20% CV)**
```{r fig.show="hold", out.width="50%"}
par(mfrow = c(1, 2))
plot(sparse4pt_covar.nlme, main = "UM/EM Sparse (4pt, 0% CV)")
plot(sparse4pt_CV5_covar.nlme, main = "UM/EM Sparse (4pt, 5% CV)")
plot(sparse4pt_CV10_covar.nlme, main = "UM/EM Sparse (4pt, 10% CV)")
plot(sparse4pt_CV20_covar.nlme, main = "UM/EM Sparse (4pt, 20% CV)")
```
\newpage
# **Final Model Residual Plots (IM/PM)**
## **Rich Study Designs (IM/PM, 0-20% CV)**
```{r fig.show="hold", out.width="50%"}
par(mfrow = c(1, 2))
plot(PM_covar.nlme, main = "IM/PM Rich (0% CV)")
plot(PM_CV5_covar.nlme, main = "IM/PM Rich (5% CV)")
plot(PM_CV10_covar.nlme, main = "IM/PM Rich (10% CV)")
plot(PM_CV20_covar.nlme, main = "IM/PM Rich (20% CV)")
```
\newpage
## **Sparse Study Designs (IM/PM, 3pt, 0-20% CV)**
```{r fig.show="hold", out.width="50%"}
par(mfrow = c(1, 2))
plot(PM_3pt_covar.nlme, main = "IM/PM Sparse (3pt, 0% CV)")
plot(PM_3pt_CV5_covar.nlme, main = "IM/PM Sparse (3pt, 5% CV)")
plot(PM_3pt_CV10_covar.nlme, main = "IM/PM Sparse (3pt, 10% CV)")
plot(PM_3pt_CV20_covar.nlme, main = "IM/PM Spase (3pt, 20% CV)")
```
\newpage
## **Sparse Study Designs (IM/PM, 4pt, 0-20% CV)**
```{r fig.show="hold", out.width="50%"}
par(mfrow = c(1, 2))
plot(PM_4pt_covar.nlme, main = "IM/PM Sparse (4pt, 0% CV)")
plot(PM_4pt_CV5_covar.nlme, main = "IM/PM Sparse (4pt, 5% CV)")
plot(PM_4pt_CV10_covar.nlme, main = "IM/PM Sparse (4pt, 10% CV)")
plot(PM_4pt_CV20_covar.nlme, main = "IM/PM Sparse (4pt, 20% CV)")
```
\newpage
# **Predicted vs Observed Plots by CYP2D6 Genotype (UM/EM)**
## **Rich Study Designs**
```{r fig.show="hold", out.width="50%"}
par(mfrow = c(1, 2))
plot(rich_covar.nlme,log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), main = "Rich (0% CV)",
xlab = "log(Fitted values)")
plot(rich_CV5_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), main = "Rich (5% CV)",
xlab = "log(Fitted values)")
plot(rich_CV10_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), main = "Rich (10% CV)",
xlab = "log(Fitted values)")
plot(rich_CV20_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), main = "Rich (20% CV)",
xlab = "log(Fitted values)")
```
\newpage
## **Sparse Study Designs (3pt)**
```{r fig.show="hold", out.width="50%"}
par(mfrow = c(1, 2))
plot(sparse3pt_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), main = "Sparse (3pt, 0% CV)",
xlab = "log(Fitted values)")
plot(sparse3pt_CV5_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), main = "Sparse (3pt, 5% CV)",
xlab = "log(Fitted values)")
plot(sparse3pt_CV10_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), main = "Sparse (3pt, 10% CV)",
xlab = "log(Fitted values)")
plot(sparse3pt_CV20_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), main = "Sparse (3pt, 20% CV)",
xlab = "log(Fitted values)")
```
\newpage
## **Sparse Study Designs (4pt)**
```{r fig.show="hold", out.width="50%"}
par(mfrow = c(1, 2))
plot(sparse4pt_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), main = "Sparse (4pt, 0% CV )",
xlab = "log(Fitted values)")
plot(sparse4pt_CV5_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), main = "Sparse (4pt, 5% CV)",
xlab = "log(Fitted values)")
plot(sparse4pt_CV10_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), main = "Sparse (4pt, 10% CV)",
xlab = "log(Fitted values)")
plot(sparse4pt_CV20_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), main = "Sparse (4pt, 20% CV)",
xlab = "log(Fitted values)")
```
\newpage
# **Predicted vs Observed Plots by CYP2D6 Genotype (IM/PM)**
## **Rich Study Designs**
```{r fig.show="hold", out.width="50%"}
par(mfrow = c(1, 2))
plot(PM_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), xlab = "log(Fitted values)",
main = "PM Rich (0% CV)")
plot(PM_CV5_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), xlab = "log(Fitted values)",
main = "PM Rich (5% CV)")
plot(PM_CV10_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), xlab = "log(Fitted values)",
main = "PM Rich (10% CV)")
plot(PM_CV20_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), xlab = "log(Fitted values)",
main = "PM Rich (20% CV)")
```
\newpage
## **Sparse Study Designs (3pt)**
```{r fig.show="hold", out.width="50%"}
par(mfrow = c(1, 2))
plot(PM_3pt_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), xlab = "log(Fitted values)",
main = "PM Sparse (3pt, 0% CV)")
plot(PM_3pt_CV5_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), xlab = "log(Fitted values)",
main = "PM Sparse (3pt, 5% CV)")
plot(PM_3pt_CV10_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), xlab = "log(Fitted values)",
main = "PM Sparse (3pt 10% CV)")
plot(PM_3pt_CV20_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), xlab = "log(Fitted values)",
main = "PM Sparse (3pt, 20% CV)")
```
\newpage
## **Sparse Study Designs (4pt)**
```{r fig.show="hold", out.width="50%"}
par(mfrow = c(1, 2))
plot(PM_4pt_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), xlab = "log(Fitted values)",
main = "PM Sparse (4pt, 0% CV)")
plot(PM_4pt_CV5_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), xlab = "log(Fitted values)",
main = "PM Sparse (4pt, 5% CV)")
plot(PM_4pt_CV10_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), xlab = "log(Fitted values)",
main = "PM Sparse (4pt, 10% CV)")
plot(PM_4pt_CV20_covar.nlme, log(V)~log(fitted(.))|Diplotype,
abline = c(0,1), xlab = "log(Fitted values)",
main = "PM Sparse (4pt, 20% CV)")
```