ArticleCell2025
Human interpretable grammar encodes multicellular systems biology models to democratize virtual cell laboratories.
Abstract read
In one paragraph
Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed.
- Artificial intelligence virtual bone organoids (AIVBOs).Journal of orthopaedic translation · 2026Review
- Topologically-based parameter inference for agent-based model selection from spatiotemporal cellular data.PLoS computational biology · 2026Article
- Interpreting Pulmonary Hypertension Beyond Single Cells.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- A Hierarchical Multimodal Knowledge Graph for Neural Cell-Type-Specific Regulation Integrating Single-Cell Transcriptomics and Literature Evidence.International journal of molecular sciences · 2026Article
- Cancer-Associated Fibroblasts Promote Epithelial-Mesenchymal Transition and Classical to Basal Subtype Shift in Pancreatic Cancer.Cancer research · 2026Article
- Preclinical and Virtual Models of Mucosal Melanoma: Bridging Translational Gaps in a Rare and Lethal Cancer.Pigment cell & melanoma research · 2026Review
- Intelligent tool orchestration for rapid mechanistic model prototyping: MCP servers as AI-biology interfaces.NPJ systems biology and applications · 2026Article
- Digital twins to accelerate target identification and drug development for immune-mediated disorders.FEBS open bio · 2026Review
- Article
- Multiscale predictive cellular modeling: integrating hypothesis grammars, digital twins, and multi-omics for In silico oncology and precision theranostics.Functional & integrative genomics · 2026Review
- A Guide for Spatial Omics Technologies: Innovation, Evaluation, and Application.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Beyond the Cell Atlas: Functional Communities as the Essential Pathologic Units Driving Kidney Disease.Journal of the American Society of Nephrology : JASN · 2026Review
- Tumor-immune trajectory context connects static tissue architecture to clinical outcomes.bioRxiv : the preprint server for biology · 2026Article
- Deep Learning Enabled 3D Multi-Omic Analysis Reveals Molecular Signatures of Heterogeneous Response to Chemotherapy in Pancreatic Cancer.bioRxiv : the preprint server for biology · 2026Article
- Mapping multipathology via spatial omic integration.Current opinion in biotechnology · 2026Review
- Data driven network inference and longitudinal transcriptomics unveil dynamic regulation in Chronic Lymphocytic Leukaemia models.NPJ systems biology and applications · 2026Article
- A Phenotype-Structured PDE Framework for Investigating the Role of Hypoxic Memory on Tumor Invasion under Cyclic Hypoxia.Bulletin of mathematical biology · 2026Article
- Mathematical modeling of combinatorial antigen targeting with multiple CAR T-cell products for glioblastoma treatment.NPJ systems biology and applications · 2026Article
- Drug-loaded nanoparticles for cancer therapy: A high-throughput multicellular agent-based modeling study.Journal of theoretical biology · 2026Article
- Trajectory Landscapes for Therapeutic Strategy Design in Agent-Based Tumor Microenvironment Models.IEEE control systems letters · 2026Article
Corrections and comments
- Update of
Authors and funding
47 authors.
Jeanette A I JohnsonDepartment 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.
Daniel R BergmanDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Department of Pharmacology, Physiology, and Drug Development, University of Maryland School of Medicine, 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; University of Maryland Institute of Health Computing, University of Maryland School of Medicine, Baltimore, MD, USA.
Heber L RochaDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN, USA.
David L ZhouDepartment of Neuroscience, Johns Hopkins University, Baltimore, MD, USA.
Eric CramerDepartment of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA.
Ian C McleanDepartment of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA.
Yoseph W DanceDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
Max BoothDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Zachary NicholasDepartment of Neuroscience, Johns Hopkins University, Baltimore, MD, USA; Department of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA.
Tamara Lopez-VidalDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Atul DeshpandeDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD, USA; Data Science and AI Institute, Johns Hopkins University, Baltimore, MD, USA.
Randy HeilandDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN, USA.
Elmar BucherDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN, USA.
Fatemeh ShojaeianDepartment of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Matthew DunworthDepartment of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
André ForjazDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Michael GetzDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN, USA.
Inês GodetMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Furkan KurtogluDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN, USA.
Melissa LymanDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA.
John MetzcarDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN, USA; Department of Informatics, Indiana University, Bloomington, IN, USA.
Jacob T MitchellDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Department of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA.
Andrew RaddatzDepartment of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta, GA, USA.
Jacobo SolorzanoCentre de Recherches en Cancerologie de Toulouse, Toulouse, France.
Aneequa SundusDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN, USA.
Yafei WangDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN, USA.
David G DeNardoDepartment of Medicine, Washington University Saint Louis, St. Louis, MO, USA.
Andrew J EwaldDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Giovannis Institute for Translational Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Daniele M GilkesDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Luciane T KagoharaDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA.
Ashley L KiemenDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Elizabeth D ThompsonDepartment of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Denis WirtzDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Pathology, Johns Hopkins University, Baltimore, MD, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.
Laura D WoodDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Pei-Hsun WuConvergence Institute, Johns Hopkins University, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Neeha ZaidiDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA.
Lei ZhengDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Mays Cancer Center, University of Texas Health, San Antonio, TX, USA; MD Anderson Cancer Center, San Antonio, TX, USA.
Jacquelyn W ZimmermanDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA.
Jude M PhillipDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Elizabeth M JaffeeDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA.
Joe W GrayDepartment of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Lisa M CoussensKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR, USA.
Young Hwan ChangDepartment of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Laura M HeiserDepartment of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Genevieve L Stein-O'BrienDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins University, Baltimore, MD, USA; Department of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA; Data Science and AI Institute, Johns Hopkins University, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD, USA. Electronic address: gsteinobrien@jmhi.edu.
Elana J FertigDepartment 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; University of Maryland Institute of Health Computing, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA; Data Science and AI Institute, Johns Hopkins University, Baltimore, MD, USA; Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, USA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: ejfertig@som.umaryland.edu.
Paul MacklinDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN, USA. Electronic address: macklinp@iu.edu.
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4MAn atlas of pancreatic tumorigenesis in the context of altered DNA repair occurring in high-risk individualsU01CA294548 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI BRODY, JONATHAN, FERTIG, ELANA · 2024 to 2025
$5.1MInterrogation of the Impact of Selection on the Evolution of Human PancreaticCancer Precursor LesionsU01CA271273 · NCI · JOHNS HOPKINS UNIVERSITY · PI Elana Fertig, Rachel Karchin · 2022 to 2026
$2.8MMapping the single cell state basis of metastasis in space and timeU01CA284090 · NCI · JOHNS HOPKINS UNIVERSITY · PI Andrew Josef Ewald · 2023 to 2026
$2.7MInforming mechanistic rules of agent-based models with single-cell multi-omicsU24CA284156 · NCI · TRUSTEES OF INDIANA UNIVERSITY · PI Elana Fertig, Paul T Macklin · 2024 to 2026
$2.3MResolving Spatiotemporal Determinants of Cell Specification in Corticogenesis with Latent Space MethodsR00NS122085 · NINDS · JOHNS HOPKINS UNIVERSITY · PI STEIN-O'BRIEN, GENEVIEVE LAUREN · 2023 to 2025
$697kNCI NIH HHS P30 CA008748NCI NIH HHS U01 CA271273NCI NIH HHS U01 CA284090NCI NIH HHS U01 CA294548NCI NIH HHS U24 CA284156NINDS NIH HHS R00 NS122085
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.
Indexed as
Models, BiologicalSystems BiologyComputer SimulationHumansNeoplasmsagent-based modelingcancer biologycell behavior hypothesis grammarcell behaviorscell interactionsimmunologyimmunotherapymathematical biologymathematical modelingmodeling languagemulticellular systemsmulticellular systems biologymulti-omicsphysics of multicellular biologysimulationspatial transcriptomicstissue dynamics
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.