BIWT: a bioinformatics walkthrough for embedding spatial multiomics in agent-based models for virtual cells

Daniel R Bergman; Jeanette A I Johnson; Marwa Naji; Max Booth; Heber Lima da Rocha; Atul Deshpande; Dimitrios N Sidiropoulos; Tamara Lopez-Vidal; Randy Heiland; Luciane T Kagohara; Robert A Anders; Lei Zheng; Elizabeth M Jaffee; Genevieve Stein-O'Brien; Paul Macklin; Elana J Fertig

doi:10.1093/bioinformatics/btaf571

BIWT: a bioinformatics walkthrough for embedding spatial multiomics in agent-based models for virtual cells

Bioinformatics. 2025 Nov 1;41(11):btaf571. doi: 10.1093/bioinformatics/btaf571.

Authors

Daniel R Bergman^{1

2

3

4

5

6}, Jeanette A I Johnson^{1

2

3}, Marwa Naji^{7

8}, Max Booth¹, Heber Lima da Rocha⁹, Atul Deshpande^{1

2}, Dimitrios N Sidiropoulos^{1

2}, Tamara Lopez-Vidal¹, Randy Heiland⁹, Luciane T Kagohara^{1

2}, Robert A Anders^{1

2

10}, Lei Zheng^{1

2}, Elizabeth M Jaffee^{1

2}, Genevieve Stein-O'Brien^{1

2

11

12}, Paul Macklin⁹, Elana J Fertig^{1

2

3

4

5

8

13

14}

Affiliations

¹ Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, 21218, United States.
² Convergence Institute, Johns Hopkins University, Baltimore, MD, 21218, United States.
³ Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, United States.
⁴ Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, 21201, United States.
⁵ Institute for Health Computing, University of Maryland School of Medicine, North Bethesda, MD, 20852, United States.
⁶ Department of Pharmacology & Physiology, University of Maryland School of Medicine, Baltimore, MD, 21201, United States.
⁷ Department of Biology, Johns Hopkins University, Baltimore, MD, 21218, United States.
⁸ Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, 21218, United States.
⁹ Department of Intelligent Systems Engineering, Indiana University, Bloomington, IN, 47408, United States.
¹⁰ Department of Pathology, Johns Hopkins University, Baltimore, MD, 21231, United States.
¹¹ Department of Neuroscience, Johns Hopkins University, Baltimore, MD, 21205, United States.
¹² Department of Human Genetics, Johns Hopkins University, Baltimore, MD, 21218, United States.
¹³ Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21218, United States.
¹⁴ Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, United States.

Abstract

Summary: Whereas transcriptomic and spatial profiling offer static snapshots of tissue structure, mechanistic models use biological rules to predict how tissues evolve. We present the BioInformatics WalkThrough (BIWT) software to directly initialize spatial agent-based models from single-cell and spatial molecular data. We demonstrate how initialization strategies affect tumor-immune dynamics and spatial clustering, positioning BIWT as a software suite to generate data-driven virtual cells representing both experimental and clinical contexts.

Availability and implementation: The BIWT software is available at https://github.com/PhysiCell-Tools/PhysiCell-Studio. The sample dataset for running the BIWT is available at https://zenodo.org/records/16365625. The code and instructions for reproducing the use case example is available at https://github.com/drbergman/BIWT-Paper.

MeSH terms

Computational Biology* / methods
Humans
Models, Biological*
Multiomics
Neoplasms / genetics
Neoplasms / immunology
Neoplasms / pathology
Single-Cell Analysis
Software*

Grants and funding

National Cancer Institute - Cancer Center Support