Dataset Information

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.

SUBMITTER: Wang Z

PROVIDER: S-EPMC5113041 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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An Observation-Driven Agent-Based Modeling and Analysis Framework for C. elegans Embryogenesis.

Wang Zi Z Ramsey Benjamin J BJ Wang Dali D Wong Kwai K Li Husheng H Wang Eric E Bao Zhirong Z

PloS one 20161116 11

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. elegan ...[more]

PMID: 27851808

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Project description:Mechanics plays a key role in the development of higher organisms. However, understanding this relationship is complicated by the difficulty of modeling the link between local forces generated at the subcellular level and deformations observed at the tissue and whole-embryo levels. Here we propose an approach first developed for lipid bilayers and cell membranes, in which force-generation by cytoskeletal elements enters a continuum mechanics formulation for the full system in the form of local changes in preferred curvature. This allows us to express and solve the system using only tissue strains. Locations of preferred curvature are simply related to products of gene expression. A solution, in that context, means relaxing the system's mechanical energy to yield global morphogenetic predictions that accommodate a tendency toward the local preferred curvature, without a need to explicitly model force-generation mechanisms at the molecular level. Our computational framework, which we call SPHARM-MECH, extends a 3D spherical harmonics parameterization known as SPHARM to combine this level of abstraction with a sparse shape representation. The integration of these two principles allows computer simulations to be performed in three dimensions on highly complex shapes, gene expression patterns, and mechanical constraints. We demonstrate our approach by modeling mesoderm invagination in the fruit-fly embryo, where local forces generated by the acto-myosin meshwork in the region of the future mesoderm lead to formation of a ventral tissue fold. The process is accompanied by substantial changes in cell shape and long-range cell movements. Applying SPHARM-MECH to whole-embryo live imaging data acquired with light-sheet microscopy reveals significant correlation between calculated and observed tissue movements. Our analysis predicts the observed cell shape anisotropy on the ventral side of the embryo and suggests an active mechanical role of mesoderm invagination in supporting the onset of germ-band extension.

Project description:Caenorhabditis elegans, often referred to as the 'roundworm', provides a powerful model for studying cell autonomous and cell-cell interactions through the direct observation of embryonic development in vivo. By leveraging the precisely mapped cell lineage at single cell resolution, we are able to study at a systems level how early embryonic cells communicate across morphogenetic domains for the coordinated processes of gene expressions and collective cellular behaviors that regulate tissue morphogenesis. In this study, we developed a computational framework for the exploration of the morphogenetic domain cell signaling networks that may regulate C. elegans gastrulation and embryonic organogenesis. We demonstrated its utility by producing the following results, i) established a virtual reference model of developing C. elegans embryos through the spatiotemporal alignment of individual embryo cell nuclear imaging samples; ii) integrated the single cell spatiotemporal gene expression profile with the established virtual embryo model by data pooling; iii) trained a Machine Learning model (Random Forest Regression), which predicts accurately the spatial positions of the cells given their gene expression profiles for a given developmental time (e.g. total cell number of the embryo); iv) enabled virtual 4-dimensional tomographic graphical modeling of single cell data; v) inferred the biology signaling pathways that act in each of morphogenetic domains by meta-data analysis. It is intriguing that the morphogenetic domain cell signaling network seems to involve some crosstalk of multiple biology signaling pathways during the formation of tissue boundary pattern. Lastly, we developed the Software tool 'Embryo aligner version 1.0' and provided it as an Open Source program to the research community for virtual embryo modeling, and phenotype perturbation analyses (https://github.com/csniuben/embryo_aligner/wiki and https://bioinfo89.github.io/C.elegansEmbryonicOrganogenesisweb/).

Dataset Information

An Observation-Driven Agent-Based Modeling and Analysis Framework for C. elegans Embryogenesis.

Publications

An Observation-Driven Agent-Based Modeling and Analysis Framework for C. elegans Embryogenesis.

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