Before I get to my actual question I'm going to try to provide the relevant context.

In terms of actual data I'm dealing with what is essentially a case-control study with WES in which variants are heavily annotated. I'm interested in looking at comparing case vs. control (diseased vs. non-diseased) via rare pathogenic variation in ~100 genes that are physiologically related to the disease within the context of their protein protein interaction network.

What I would like to do is be able to generate simulated exomes where I can control the amount/severity of pathogenic variants within these ~100 genes, while being able to impose rules/biases on the deposition of the variants within the PPI network. For example, bias the variants towards genes/protiens with higher node centrality within PPI network.

Now, I know there's not going to be a program out there that can actually do all of this for me. However I'm a bit lost on where to start. I've been trying to find a tool that can at least just help me do the first part. So I can simulate the simplest case, so to speak, in which I just simulate exomes with a range of rare variants numbers within these genes that I can either assign pathogenicity scores to or if it actually simulates variant info, score with CADD. I could then work on further parameterizing the model myself.

I've tried searching for awhile now, but I feel like I'm at that stage where I don't know what I don't know, so any help or advice would be much appreciated.