VIS-A-VIS is an agent-based simulator of viral infection spread and viral infection self-containment in a monolayer of cell.

The simulation mimics the innate immune response to an infection with an RNA virus. The hard-coded and externally parametrized interactions between the host cell and virus are specific to the respiratory syncytial virus (RSV) and human alveolar epithelial cells (A549 cell line). Infected cells attempt to produce and secrete an interferon, which alerts the non-infected bystander cells about the nearby threat.

VIS-A-VIS is a hybrid simulator as it executes alternating phases of interferon diffusion and chemical kinetics. The interferon diffuses between compartments above neighboring lattice nodes and its local concentrations are expressed using real variables. The nodes are occupied by cells, in which stochastic chemical kinetics (Gillespie algorithm) causes transitions within a predefined set of states for molecules of several chemical species. Some of these states are associated with higher level or higher activity of these molecules. The lattice has periodic boundary conditions.

VIS-A-VIS was used in the paper "Antagonism between viral infection and innate immunity at the single-cell level", PLOS Pathogens (2023). See citing section below.

The simulator has been implemented in Rust. If your Rust toolchain has been set up via rustup, then prior to compilation in the command line you may want to issue:

$ rustup update

To compile the source code, enter the visavis-1.0.0 folder and type:

$ cargo build --release

The software has been tested to successfully compile under the current stable toolchain (shipping rustc version 1.64.0). If libglib2.0-dev and libcairo2-dev are installed, all dependencies (rust crates) should be retrieved and compiled on the fly.

To run a simulation using default parameters and stimulation protocol, you may invoke the simulator with:

$ cargo run --release parameters/default.json protocols/default.protocol --images

which is equivalent to:

$ target/release/vis-a-vis parameters/default.json protocols/default.protocol --images

At simulated-time intervals prescribed in the protocol, the simulator produces CSV-formatted files with the current state of all molecules in the lattice. Generating PNG images with lattice snapshots (turned on when using the --images argument) is optional.

CSV: Each generated CSV file fully describes the state of the simulated system in the time point specified in the file name. Each row of the file corresponds to a lattice node that contains a cell, whose molecular internal state is given in comma-separated entries corresponding to molecules as given in the file header. States of molecules are discrete (and are in the range MIN..MAX defined in respective arrays in src/cell.rs). Last two columns give the amount of the extracellular interferon in the cell culture medium above the cell-node (in the lower and in the upper subcompartment separately).

PNG: Lattice images depict cells as circles inscribed in hexagons. The more yellow is the hexagon fill, the higher is the amount of the extracellular interferon in the lower medium subcompartment above the cell. Pinkish outer cell ring indicates viral infection; reddish color of the inner circle corresponds to a high level of p-IRF3, whereas greenish inner circle shows STAT1/2 activity.

If in module lattice (src/lattice.rs) the boolean variable Lattice::NEIGHS_TO_FILE is set to true, then additionally a file neighbors.csv with complete information about lattice node neighborhoods is dumped.

All the output files are generated in the current working directory.

Changes in stimulation protocols (provided as text files, see included examples in protocols/) or in parameter values (provided as JSON-formatted text files, see examples included in parameters/) do not require the code to be recompiled.

Modifications of the wiring of the molecular virus--host and intra-host interactions require changes in module simulation (src/simulation.rs) and code recompilation.

To change lattice size, you need not only to change Lattice::WIDTH, Lattice::HEIGHT in module lattice (src/lattice.rs), but also likely tweak the THREAD_STACK_SIZE parameter in module config (src/config.rs), and then recompile the code.

Since running many simulations from terminal can be cumbersome, in extra/ we provide a simple Python wrapper and associated convenience code for working with Vis-A-Vis:

• visavis.py: the Vis-A-Vis client,
• simulation_result.py: class wrapping the result of a simulation,
• annotate.py: script for annotating lattice snapshots,
• parameters/default.py: Python format for parameters.

Script extra/example.py demonstrates concisely how the convenience code may be used. The script can be run with:

$ cd extra/
$ python example.py

The simulator, written by Marek Kochanczyk and Frederic Grabowski from the Institute of Fundamental Technological Research of the Polish Academy of Sciences (IPPT PAN, Warsaw, Poland), features the research article "Antagonism between viral infection and innate immunity at the single-cell level" published in PLOS Pathogens (2023). If you use the code for research purposes, please consider citing this work.

The code is open source under the 3-Clause BSD license (see file LICENSE or visit https://opensource.org/licenses/BSD-3-Clause).