A statistical approach to estimating the strength of cell-cell interactions under the differential adhesion hypothesis
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A statistical approach to estimating the strength of cell-cell interactions under the differential adhesion hypothesis Mathieu Emily*1,2 and Olivier François1 Address: 1TIMC-TIMB, Université Joseph Fourier, INP Grenoble, Faculty of Medicine, 38706 La Tronche cedex, France and 2Bioinformatics Research Center (BiRC), University of Aarhus, Hoegh-Guldbergs Gade 10, 8000 Aarhus C, Denmark Email: Mathieu Emily* - [email protected]; Olivier François - [email protected] * Corresponding author
Published: 18 September 2007 Theoretical Biology and Medical Modelling 2007, 4:37
doi:10.1186/1742-4682-4-37
Received: 23 April 2007 Accepted: 18 September 2007
This article is available from: http://www.tbiomed.com/content/4/1/37 © 2007 Emily and François; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: The Differential Adhesion Hypothesis (DAH) is a theory of the organization of cells within a tissue which has been validated by several biological experiments and tested against several alternative computational models. Results: In this study, a statistical approach was developed for the estimation of the strength of adhesion, incorporating earlier discrete lattice models into a continuous marked point process framework. This framework allows to describe an ergodic Markov Chain Monte Carlo algorithm that can simulate the model and reproduce empirical biological patterns. The estimation procedure, based on a pseudo-likelihood approximation, is validated with simulations, and a brief application to medulloblastoma stained by beta-catenin markers is given. Conclusion: Our model includes the strength of cell-cell adhesion as a statistical parameter. The estimation procedure for this parameter is consistent with experimental data and would be useful for high-throughput cancer studies.
Background The development and the maintenance of multi-cellular organisms are driven by permanent rearrangements of cell shapes and positions. Such rearrangements are a key step for the reconstruction of functional organs [1]. In vitro experiments such as Holtfreter's experiments on the pronephros [2] and the famous example of an adult living organism Hydra [3] are illustrations of spectacular spontaneous cell sorting. Steinberg [4-7] used the ability of cells to self-organize in coherent structures to conduct a series of pioneering experimental studies that characterized cell adhesion as a major actor of cell sorting. Following his experiments, Steinberg suggested that the interaction between two cells involves an adhesion surface energy which varies according to the cell type. To
interpret cell sorting, Steinberg formulated the Differential Adhesion Hypothesis (DAH), which states that cells can explore various configurations and fina
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