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Updated: Sep 13, 2025

A Web Tool for Generating High Quality Machine-readable Biological Pathways
Published on: February 8, 2017
Human interpretable grammar encodes multicellular systems biology models to democratize virtual cell laboratories
Jeanette A I Johnson1, Daniel R Bergman2, Heber L Rocha3
1Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA; Marlene & Stuart Greenbaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Abstract:
Cells interact as dynamically evolving ecosystems. While recent single-cell and spatial multi-omics technologies quantify individual cell characteristics, predicting their evolution requires mathematical modeling. We propose a conceptual framework-a cell behavior hypothesis grammar-that uses natural language statements (cell rules) to create mathematical models. This enables systematic integration of biological knowledge and multi-omics data to generate in silico models, enabling virtual "thought experiments" that test and expand our understanding of multicellular systems and generate new testable hypotheses. This paper motivates and describes the grammar, offers a reference implementation, and demonstrates its use in developing both de novo mechanistic models and those informed by multi-omics data. We show its potential through examples in cancer and its broader applicability in simulating brain development. This approach bridges biological, clinical, and systems biology research for mathematical modeling at scale, allowing the community to predict emergent multicellular behavior.
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