A semi-mechanistic model of CRISPR perturbation screens, built from editing, media, and waiting operations, improves gene-expression prediction when trained with an extra steady-state constraint.
DiscoGen: Learning to Discover Gene Regulatory Networks
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abstract
Accurately inferring Gene Regulatory Networks (GRNs) is a critical and challenging task in biology. GRNs model the activatory and inhibitory interactions between genes and are inherently causal in nature. To accurately identify GRNs, perturbational data is required. However, most GRN discovery methods only operate on observational data. Recent advances in neural network-based causal discovery methods have significantly improved causal discovery, including handling interventional data, improvements in performance and scalability. However, applying state-of-the-art (SOTA) causal discovery methods in biology poses challenges, such as noisy data and a large number of samples. Thus, adapting the causal discovery methods is necessary to handle these challenges. In this paper, we introduce DiscoGen, a neural network-based GRN discovery method that can denoise gene expression measurements and handle interventional data. We demonstrate that our model outperforms SOTA neural network-based causal discovery methods.
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cs.LG 1years
2025 1verdicts
CONDITIONAL 1representative citing papers
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No Foundations without Foundations -- Why semi-mechanistic models are essential for regulatory biology
A semi-mechanistic model of CRISPR perturbation screens, built from editing, media, and waiting operations, improves gene-expression prediction when trained with an extra steady-state constraint.