MultiCellDS: a community-developed standard for curating microenvironment-dependent multicellular data

Abstract

Abstract:Exchanging and understanding scientific data and their context represents a significant barrier to advancing research, especially with respect to information siloing. Maintaining information provenance and providing data curation and quality control help overcome common concerns and barriers to the effective sharing of scientific data. To address these problems in and the unique challenges of multicellular systems, we assembled a panel composed of investigators from several disciplines to create the MultiCellular Data Standard (MultiCellDS) with a use-case driven development process. The standard includes (1) digital cell lines, which are analogous to traditional biological cell lines, to record metadata, cellular microenvironment, and cellular phenotype variables of a biological cell line, (2) digital snapshots to consistently record simulation, experimental, and clinical data for multicellular systems, and (3) collections that can logically group digital cell lines and snapshots. We have created a MultiCellular DataBase (MultiCellDB) to store digital snapshots and the 200+ digital cell lines we have generated. MultiCellDS, by having a fixed standard, enables discoverability, extensibility, maintainability, searchability, and sustainability of data, creating biological applicability and clinical utility that permits us to identify upcoming challenges to uplift biology and strategies and therapies for improving human health.

High-throughput cancer hypothesis testing with an integrated PhysiCell-EMEWS workflow

“…Also, the generalized description of hypotheses is not yet fully mature. Standards have emerged to describe molecularscale systems biology (generally systems of ODEs) as SBML [49], and more recently to express multicellular biology as MultiCellDS [39,40], but cell-cell interaction rules will likely require a different description, such as by using elements of the cell behavior ontology (CBO) [51].…”

“…In [1], we developed a 3-D agent-based model by extending BioFVM's basic agents (discrete cell-like agents with static positions, which could secrete and consume chemical substrates in the BioFVM environment) to create extensible software cell agents. Each cell has an independent, hierarchically-organized phenotype (the cell's behavioral state and parameters) [39,40], user-settable function pointers to define hypotheses on the cell's phenotype, volume changes, cell cycling or death, mechanics, orientation, and motility, and user-customizable data. The cells' function pointers can be changed at any time in the simulation, allowing dynamical cell behavior and even switching between cell types.…”

PhysiCell: an Open Source Physics-Based Cell Simulator for 3-D Multicellular Systems

“…47 PhysiCell aims to balance computational speed, built-in standard functionality, 48 flexibility, and codebase simplicity. It includes a built-in library of standardized cell 49 cycle and cell death models co-developed with biologists and modelers here and in the 50 MultiCellDS standardization process [14,15], force-based cell-cell interaction mechanics, 51 motility, and volume regulation. Users can replace any of these built-in models with 52 their own, and they can dynamically assign custom functions to any agent at any time.…”

“…(See Cell 401 cycling.) We used a simpler "live cells" cycle model [14] Hanging drop spheroids (HDS)-a 3-D cell culture model where a small cluster or 422 aggregate of tumor cells is suspended in a drop of growth medium by surface tension-are 423 increasingly used to approximate 3-D in vivo growth conditions [31]. Unlike traditional 424 2-D monolayer experiments, HDSs allow scientists to investigate the impact of substrate 425 gradients on tumor growth, particularly oxygen gradients.…”

“…Software limitations and potential solutions PhysiCell is intended to function as a 666 modular engine and to interact with standardized data (e.g., MultiCellDS [14]), but it has 667 not yet fully implemented MultiCellDS import and export. Graphical simulation design 668 tools, data visualization tools, and analysis tools are needed to widen its accessibility 669 beyond seasoned C++ programmers and reduce its learning curve.…”