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.

Agent-based models (ABMs) have become essential tools for simulating complex biological, ecological, and social systems where emergent behaviors arise from the interactions among individual agents. Quantifying uncertainty through global sensitivity analysis is crucial for assessing the robustness and reliability of ABM predictions. However, most global sensitivity methods demand substantial computational resources, making them impractical for highly complex models. Here, we introduce SMoRe GloS (Surrogate Modeling for Recapitulating Global Sensitivity), a novel, computationally efficient method for performing global sensitivity analysis of ABMs. By leveraging explicitly formulated surrogate models, SMoRe GloS allows for comprehensive parameter space exploration and uncertainty quantification without sacrificing accuracy. We demonstrate our method's flexibility by applying it to two biological ABMs: a simple 2D in vitro cell proliferation model and a complex 3D vascular tumor growth model. Our results show that SMoRe GloS is compatible with simpler methods like the Morris one-at-a-time method, and more computationally intensive variance-based methods like eFAST. SMoRe GloS accurately recovered global sensitivity indices in each case while achieving substantial speedups, completing analyses in minutes. In contrast, direct implementation of eFAST amounted to several days of CPU time for the complex ABM. Remarkably, our method also estimates sensitivities for ABM parameters representing processes not explicitly included in the surrogate model, further enhancing its utility. By making global sensitivity analysis feasible for computationally expensive models, SMoRe GloS opens up new opportunities for uncertainty quantification in complex systems, allowing for more in depth exploration of model behavior, thereby increasing confidence in model predictions.

[This corrects the article DOI: 10.1371/journal.pcbi.1013427.].

Advancements in imaging technologies have revolutionized our ability to deeply profile pathological tissue architectures, generating large volumes of imaging data with unparalleled spatial resolution. This type of data collection, namely, spatial proteomics, offers invaluable insights into various human diseases. Simultaneously, computational algorithms have evolved to manage the increasing dimensionality of spatial proteomics inherent in this progress. Numerous imaging-based computational frameworks, such as computational pathology, have been proposed for research and clinical applications. However, the development of these fields demands diverse domain expertise, creating barriers to their integration and further application. This review seeks to bridge this divide by presenting a comprehensive guideline. We consolidate prevailing computational methods and outline a roadmap from image processing to data-driven, statistics-informed biomarker discovery. Additionally, we explore future perspectives as the field moves toward interfacing with other quantitative domains, holding significant promise for precision care in immuno-oncology.