---
title: "Simulation study from empirical data with penetrance"
author: "BayesMendel Lab"
output: rmarkdown::html_vignette
vignette: >
  %\VignetteIndexEntry{Simulation study from empirical data with penetrance}
  %\VignetteEngine{knitr::rmarkdown}
  %\VignetteEncoding{UTF-8}
---

```{r setup, include=FALSE}
knitr::opts_chunk$set(echo = TRUE)
library(penetrance)
library(ggplot2)
library(scales)
```

## Goal

Here we apply the penetrance package to simulated families where the data-generating
penetrance function is known and based on existing penetrance estimates.

## Simulated Data

The data-generating distribution of the age-specific penetrances is based on 
existing penetrance estimates for Colorectal cancer in carriers of any pathogenic 
variant in MLH1 from the Fam3PRO Database. 

The families were simulated using the PedUtils Rpackage.   

```{r}
dat <- test_fam2
# geno column must be Geno
dat <- lapply(dat, function(df) {
  names(df)[names(df) == "geno"] <- "Geno"
  df
})
```
  
## Simple simulation

Then we run the estimation using the default settings. 

```{r, eval=FALSE}
# Set the random seed
set.seed(2024)

# Set the prior
prior_params <- list(
    asymptote = list(g1 = 1, g2 = 1),
    threshold = list(min = 5, max = 30),
    median = list(m1 = 2, m2 = 2),
    first_quartile = list(q1 = 6, q2 = 3)
)

# Set the allele frequency for MLH1 based on Fam3PRO Database
prevMLH1 <- 0.0004453125 

# We use the default baseline (non-carrier) penetrance
print(baseline_data_default)

# We run the estimation procedure with one chain and 20k iterations  
out_sim <- penetrance(
    pedigree  = dat, twins = NULL, n_chains = 1, n_iter_per_chain = 20000, 
    ncores = 2, baseline_data = baseline_data_default , allele_freq = prevMLH1, 
    prior_params = prior_params, burn_in = 0.1, median_max = TRUE,  
    age_imputation = FALSE, remove_proband = FALSE
)
```

## References

Lee G, Liang JW, Zhang Q, Huang T, Choirat C, Parmigiani G, Braun D. Multi-syndrome,
multi-gene risk modeling for individuals with a family history of cancer with 
the novel R package Fam3PRO. Elife. 2021;10:e68699. doi:10.7554/eLife.6869