Large amounts of knowledge regarding biological processes are readily available in the literature and aggregated in diverse databases. Boolean networks are powerful tools to render that knowledge into models that can mimic and simulate biological phenomena at multiple scales. Yet, when a model is required to understand or predict the behavior of a biological system in given conditions, existing information often does not completely match this context. Networks built from only prior knowledge can overlook mechanisms, lack specificity, and just partially recapitulate experimental observations. To address this limitation, context-specific data needs to be integrated. However, the brute-force identification of qualitative rules matching these data becomes infeasible as the number of candidates explodes for increasingly complex systems. Here, we used Zhegalkin polynomials to transform this identification into a binary value assignment for exponentially fewer variables, which we addressed with a state-of-the-art SAT solver. We evaluated our implemented method alongside two widely recognized tools, CellNetOptimizer and Caspo-ts, on both artificial toy models and large-scale models based on experimental data from the HPN-DREAM challenge. Our approach demonstrated benchmark-leading capabilities on networks of significant size and intricate complexity. It thus appears promising for the in silico modeling of ever more comprehensive biological systems.

Motivation: Flow, hyperspectral and mass cytometry are experimental techniques measuring cell marker expressions at the single cell level. The recent increase of the number of markers simultaneously measurable has led to the development of new automatic gating algorithms. Especially, the SPADE algorithm has been proposed as a novel way to identify clusters of cells having similar phenotypes in high-dimensional cytometry data. While SPADE or other cell clustering algorithms are powerful approaches, complementary analysis features are needed to better characterize the identified cell clusters. Results: We have developed SPADEVizR, an R package designed for the visualization, analysis and integration of cell clustering results. The available statistical methods allow highlighting cell clusters with relevant biological behaviors or integrating them with additional biological variables. Moreover, several visualization methods are available to better characterize the cell clusters, such as volcano plots, streamgraphs, parallel coordinates, heatmaps, or distograms. SPADEVizR can also generate linear, Cox or random forest models to predict biological outcomes, based on the cell cluster abundances. Additionally, SPADEVizR has several features allowing to quantify and to visualize the quality of the cell clustering results. These analysis features are essential to better interpret the behaviors and phenotypes of the identified cell clusters. Importantly, SPADEVizR can handle clustering results from other algorithms than SPADE. Availability and Implementation: SPADEVizR is distributed under the GPL-3 license and is available at https://github.com/tchitchek-lab/SPADEVizR . Contact: [email protected]. Supplementary information: Supplementary data are available at Bioinformatics online.