From Diverse Prior Knowledge to Mechanistic Causal Network Using PSoup: A Case Study in Shoot Branching

Abstract

Mechanistic models of plant regulatory networks typically require extensive parameterization, limiting their generalisation and scalability. Here we present a parameter-free, topology-driven model of shoot branching that predicts phenotypic outcomes from network structure alone. We constructed a signed, directed causal network by distilling regulatory relationships from the published literature spanning many laboratories, species, years, data types, and methodological frameworks. This extracted the essential logic of the system, consistent with developmental-biological reasoning and anchored in empirical evidence. Using PSoup, which automatically translates network topology into algebraic equations, the model propagates information across the network and predicts the qualitative direction of change relative to a defined baseline, mirroring the comparative framework of biological experiments. The pipeline, from network construction through automated equation generation to prediction, is transparent and reproducible. Trained against branching phenotype data with 78 diverse perturbations spanning genetic mutations and hormone treatments, the model achieved 86% accuracy in predicting branching direction. On an independent test set of 84 perturbations measuring bud release and gene expression at nodes not used during training, accuracy reached 75%. The approach highlighted deficiencies in our understanding of the topology of the network around SMXL 6/7/8 and ABA nodes. Other errors came mainly from modelling choices, such as the threshold for scoring a node as changed relative to baseline. Beyond shoot branching, this work demonstrates a general strategy for synthesizing biological knowledge into validated predictive networks, providing a foundation for both applied breeding and the advancement of fundamental biology.