Cell lineage tree of simulation.

<p>Nodes represent cells with lines connecting mother and daughter cells. Length of the line represents cell cycle time.</p

Cell cycle analysis of 12 founder cells.

<p>Cell cycle analysis of 12 founder cells.</p

High level representation of framework.

<p>Two processes in the the framework, namely “setup” and “execution”. The “execution” process is further divided into a “movement” and a “division” activity.</p

Number of cells in embryo over time.

<p>Figure shows the number of cells in the simulation/real embryo from the beginning to ∼180 minutes, from 4-cell stage to ∼180-cell stage.</p

An Observation-Driven Agent-Based Modeling and Analysis Framework for <i>C. elegans</i> Embryogenesis

<div><p>With cutting-edge live microscopy and image analysis, biologists can now systematically track individual cells in complex tissues and quantify cellular behavior over extended time windows. Computational approaches that utilize the systematic and quantitative data are needed to understand how cells interact <i>in vivo</i> to give rise to the different cell types and 3D morphology of tissues. An agent-based, minimum descriptive modeling and analysis framework is presented in this paper to study <i>C. elegans</i> embryogenesis. The framework is designed to incorporate the large amounts of experimental observations on cellular behavior and reserve data structures/interfaces that allow regulatory mechanisms to be added as more insights are gained. Observed cellular behaviors are organized into lineage identity, timing and direction of cell division, and path of cell movement. The framework also includes global parameters such as the eggshell and a clock. Division and movement behaviors are driven by statistical models of the observations. Data structures/interfaces are reserved for gene list, cell-cell interaction, cell fate and landscape, and other global parameters until the descriptive model is replaced by a regulatory mechanism. This approach provides a framework to handle the ongoing experiments of single-cell analysis of complex tissues where mechanistic insights lag data collection and need to be validated on complex observations.</p></div

Cell displacement patterns during AB64 stage.

<p>3D depth trajectories represent the movement path of cells. Different colors represent the 14 founder cells of <i>C. elegans</i>, which is color coded by the following rules: ABala(light brown), ABalp(light blue), ABara(light purple), ABarp(yellow), ABpla(red), ABplp(dark blue), ABpra(magenta), ABprp(dark purple), MSa(light green), MSp(dark green), E(pink), C(dark brown), D(light gray), P(dark gray).</p

Input parameters of each table and example values.

<p>Input parameters of each table and example values.</p

Cell position validation.

<p>Stages of AB32 and AB64 mean when the AB lineage divides into 32 and 64 cells. Color-coded rule is the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0166551#pone.0166551.g006" target="_blank">Fig 6</a>. Dots represent the exact cell positions in a specific simulation/observational case, and ellipses represent the average position of each coresponding cell (with one standard deviation).</p

Analysis of dividing positions of 12 founder cells.

<p>Analysis of dividing positions of 12 founder cells.</p

Divide activity of the model.

<p>Divide activity of the model.</p