title: An Observation-Driven Agent-Based Modeling and Analysis Framework for C. elegans Embryogenesis.
abstract: 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 in vivo 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 C. elegans 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.
authors.affiliation: Department of Electrical Engineering and Computer Science, University of Tennessee, Knoxville, Tennessee, United States of America.
authors.forename: Zi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Joint Institute for Computational Sciences, University of Tennessee, Knoxville, Tennessee, United States of America.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Ramsey
authors.affiliation: Climate Change Science Institute, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States of America.
authors.forename: Dali
authors.initials: D
authors.lastname: Wang
authors.affiliation: Joint Institute for Computational Sciences, University of Tennessee, Knoxville, Tennessee, United States of America.
authors.forename: Kwai
authors.initials: K
authors.lastname: Wong
authors.affiliation: Department of Electrical Engineering and Computer Science, University of Tennessee, Knoxville, Tennessee, United States of America.
authors.forename: Husheng
authors.initials: H
authors.lastname: Li
authors.affiliation: Farragut High School, Knoxville, Tennessee, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Wang
authors.affiliation: Developmental Biology Program, Sloan Kettering Institute, New York City, New York, United States of America.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Bao
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology*; D002452:Cell Count; D002453:Cell Cycle; D019070:Cell Lineage; D002465:Cell Movement; D003198:Computer Simulation; D004625:Embryo, Nonmammalian / Q000166:cytology; D047108:Embryonic Development; D008954:Models, Biological; D015203:Reproducibility of Results; D013597:Systems Analysis