GxE_phenotype_QC.Rmd

---
output: html_document
title: Phenotype QC for gene-environment interaction testing
params:
  phenotype_file: "path_to_phenotype_file"
  outcome: "outcome_name"
  exposure: "exposure_name"
  groups: "character_vector_of_group_names"
---

<!--
Run using: rmarkdown::render("GxE_phenotype_QC.Rmd", output_file="myfile.html",
                              params=list(phenotype_file="my_phenofile.csv"))
-->

```{r setup, include=FALSE}
knitr::opts_chunk$set(echo=FALSE, message=FALSE, warning=FALSE, dev="png")
suppressMessages(silent <- lapply(
  c("knitr", "kableExtra", "data.table", "tidyverse"),
  library, character.only=TRUE))
theme_set(theme_bw())
```

```{r load-data}
if (grepl("\\.rds", params$phenotype_file)) {  # Binary .rds input file
  phenos <- readRDS(params$phenotype_file)
} else if (grepl("\\.RData", params$phenotype_file, ignore.case=TRUE)) {  # Binary .RData input file
  phenos <- get(load(params$phenotype_file))
} else {  # Otherwise, assume a flat file and let fread guess the delimiter
  phenos <- fread(params$phenotype_file, stringsAsFactors=FALSE, data.table=FALSE)
}

phenos <- filter(phenos, !is.na(.data[[outcome]]), !is.na(.data[[exposure]]))
if (length(unique(phenos[[params$outcome]])) <= 2) {  # Outcome is binary
  bin_outcome <- TRUE
  phenos[[params$outcome]] <- factor(phenos[[params$outcome]])
} else {
  bin_outcome <- FALSE
}
if (length(unique(phenos[[params$exposure]])) <= 2) {  # Exposure is binary
  bin_exposure <- TRUE
  phenos[[params$exposure]] <- factor(phenos[[params$exposure]])
} else {
  bin_exposure <- FALSE
}
phenos <- mutate_at(phenos, vars(all_of(params$groups)), factor)  # All stratification groups as factors

outcome <- params$outcome
exposure <- params$exposure
```

```{r define-functions}
make_hist <- function(pheno, df) {
  stat_type <- if (is.factor(df[[pheno]])) "count" else "bin"
  df %>%
    filter(!is.na(.data[[pheno]])) %>%
    ggplot(aes_string(x=pheno)) +
    geom_histogram(stat=stat_type)
}

make_exposure_outcome_plt <- function(pheno, xvar, df) {
  if (!bin_outcome & !bin_exposure) {
      ggplot(df, aes_string(x=xvar, y=pheno)) +
      geom_smooth()
  } else if (bin_outcome & !bin_exposure) {
      ggplot(df, aes_string(x=pheno, y=xvar)) +
      geom_boxplot()
  } else if (!bin_outcome & bin_exposure) {
      ggplot(df, aes_string(x=xvar, y=pheno)) +
      geom_boxplot()
  } else {
      ggplot(df, aes_string(x=pheno, fill=xvar)) +
      geom_histogram(stat="count", position="dodge")
  }
}

make_grouped_hist <- function(pheno, grp, df) {
  df <- filter(df, !is.na(.data[[pheno]]))
  if (is.factor(df[[pheno]])) {
    df %>%
      group_by_at(grp) %>%
      summarise(fraction = sum(.data[[pheno]] == 1) / n()) %>%
      ggplot(aes_string(x=grp, y="fraction")) +
      geom_bar(stat="identity", position="dodge", width=0.8)
  } else {
    df %>%
      mutate_at(grp, ~factor(.)) %>%
      ggplot(aes_string(x=pheno, fill=grp)) +
      geom_histogram(alpha=0.3, position="identity")
  }
}

test_assoc <- function(pheno, xvar, df) {
  form <- as.formula(paste0(pheno, " ~ ", xvar))
  fam <- if(is.factor(df[[pheno]])) "binomial" else "gaussian"
  broom::tidy(glm(form, data=df, family=fam)) 
}
```

# Outcome & exposure

```{r raw-histograms}
outcome_hist <- make_hist(outcome, phenos)
exposure_hist <- make_hist(exposure, phenos)

outcome_hist
exposure_hist
```

```{r exposure-outcome-relationship}
make_exposure_outcome_plt(outcome, exposure, phenos)
test_assoc(outcome, exposure, phenos)
```

# Outcome & strata

```{r group-outcome-relationships}
for (grp in params$groups) {
  print(make_grouped_hist(outcome, grp, phenos))
  print(test_assoc(outcome, grp, phenos))
}
```

# Exposure & strata

```{r group-exposure-relationships}
for (grp in params$groups) {
  print(make_grouped_hist(exposure, grp, phenos))
  print(test_assoc(exposure, grp, phenos))
}
```

--------------------------------------------------------------------------------

```{r dump-parameters}
tibble(Parameter=names(params),
       Value=unlist(lapply(params, paste, collapse=", "))) %>%
  kable(booktabs=TRUE,
        caption="QC report parameters") %>%
  kable_styling(full_width=FALSE)
```