PNNL

Abstract

The biomolecular networks underpinning cell function exhibit canalization, or the buffering of fluctuations required to function in a noisy environment. We present a new major release of CANA, v1.0.0, an opensource Python package for understanding canalization in automata network models, discrete dynamical systems in which activation of biomolecular entities (e.g., transcription of genes) is modeled as the activity of coupled automata. CANA supports the scalable analysis of canalization, by identifying and compressing logical redundancy at the level of individual automata. This information is subsequently aggregated to quantify and visualize how regulation, modularity, and control effectively occur in the macro-dynamics of these network models. One understudied putative mechanism for canalization is the functional equivalence of biomolecular regulators (e.g., among the transcription factors for a gene). We study this mechanism using the theory of symmetry in discrete functions. We present a new exact algorithm for finding maximal symmetry groups among the inputs to discrete functions. We implement this algorithm in Rust as a Python package, schematodes, and integrate it into the major CANA update, CANA v1.0.0. We compare schematodes to the inexact method used in previously published versions of CANA and find that schematodes substantially outperforms the prior method both in speed and accuracy. To demonstrate its utility, we apply CANA v1.0.0 to study symmetry in 74 experimentally-supported automata network models from the Cell Collective (CC) repository. We find that the symmetry distribution is significantly different in the CC than in random automata with the same in-degree (connectivity) and bias (average output) (Kolmogorov-Smirnov test, p « 0.001). In particular, its spread is much wider than in a null model (IQR 0.31 vs IQR 0.20 with equal medians), demonstrating that the CC is enriched in functions with extreme symmetry or asymmetry. Source code is available at github.com/CASCI-lab/CANA for CANA, github.com/CASCI-lab/schematodes for schematodes, and github.com/CASCI-lab/symmetryInCellCollective for analysis scripts.