Simulations of gene regulatory networks with transcriptional adaptation

Background
Cells and tissues have a remarkable ability to adapt to genetic perturbations via a variety of molecular mechanisms. Transcriptional adaptation has recently emerged as one such mechanism, in which nonsense mutations in a gene trigger upregulation of related genes, possibly conferring robustness at cellular and organismal levels. However, beyond a handful of developmental contexts and curated sets of genes, no comprehensive genome-wide investigation of this behavior has been undertaken for mammalian cell types and contexts. Further, how the regulatory-level effects of inherently stochastic compensatory gene networks contribute to phenotypic penetrance in single cells remains unclear.
Results
In the corresponding manuscript, we analyze existing bulk and single-cell transcriptomic datasets to infer the prevalence of transcriptional adaptation in mammalian systems across diverse contexts and cell types. In the data presented here, stochastic mathematical modeling of minimal compe..., The dataset was generated through simulations of gene regulatory networks with transcriptional adaptation, where genes are represented as nodes and regulatory relationships as edges. Please see the corresponding manuscript for a complete description of the model, simulation conditions, and analyses.
The regulatory networks were constructed using a modified telegraph model for transcriptional bursting, where each gene's alleles switch between active (transcribing) and inactive (quiescent) states, for an ancestral regulator gene (A), its paralogs (A'1 and A'2), and a downstream target gene (B). To capture the dynamics of gene regulation, we implemented stochastic simulations using Gillespie’s next reaction method. We accounted for differential regulatory effects of different gene products. We included models for both activating and repressing interactions, as well as models with more than one paralog gene. 
Parameter ranges were defined based on previously reported literature on transcrip..., , # **Simulations of Gene Regulatory Networks with Transcriptional Adaptation**

[https://doi.org/10.5061/dryad.nk98sf82j](https://doi.org/10.5061/dryad.nk98sf82j)

## Project Description

Outputs of simulations of gene regulatory networks with transcriptional adaptation (also known as nonsense-induced transcriptional compensation) as described in

> Mellis IA, Melzer ME, Bodkin N, and Goyal Y. 2024. Prevalence of and gene regulatory constraints on transcriptional adaptation in single cells. Genome Biology.

We performed simulations of gene regulatory networks with transcriptional adaptation, where genes are represented as nodes and regulatory relationships as edges.

The regulatory networks were constructed using a modified telegraph model for transcriptional bursting, where each gene's alleles switch between active (transcribing) and inactive (quiescent) states, for an ancestral regulator gene (A), its paralogs (A' for 1-paralog models, A'1 and A'2 for multiparalog models), and a dow...