VUS_Project

This folder includes R code to conduct simulations for "A Likelihood-based Approach to Assessing Frequency of Pathogenicity among Variants of Unknown Significance (VUS) in Susceptibility Genes".

Folders:

1. Rcode folder: all code for running simulations.

• sim_fam_varied.R: script to simulate family pedigrees based on different family structures in the main text.

• sim_fam_constant.R: script to simulate family pedigrees based on a constant family structure.

• estimate_pi.R: script to estimate the proprotion of VUS that are likely pathogenic and calculate positive predictive value in simulated data.

• estimate_pi_with_theta.R: script to esitmate the proportion of VUS that are likely pathogenic and calculate positive predictive value in simulated data with the extension of theta.

2. Results folder: 'Data' contains simulated data for Figures 1-6. It also contains scripts for generating Figure1-6.

Simulation Step:

1. Use sim_fam_varied.R to simulate family pedigree data of size N. Under each sample size, replicates are named with script_num.RData.
2. Use estimate_pi.R or estimate_pi_with_theta.R to estimate the proportion of VUS that are likely pathogenic and the positive predictive value in simulated family pedigree data.
3. Repeat step1-2 for all simulated cohort replicates.