Abstract

Three-dimensional (3D) culture models are critical tools for understanding tissue morphogenesis. A key requirement for their analysis is the ability to reconstruct the tissue into computational models that allow quantitative evaluation of the formed structures. Here, we present Software for Automated Morphological Analysis (SAMA), a method by which epithelial structures grown in 3D cultures can be imaged, reconstructed and analyzed with minimum human intervention. SAMA allows quantitative analysis of key features of epithelial morphogenesis such as ductal elongation, branching and lumen formation that distinguish different hormonal treatments. SAMA is a user-friendly set of customized macros operated via FIJI (http://fiji.sc/Fiji), an open-source image analysis platform in combination with a set of functions in R (http://www.r-project.org/), an open-source program for statistical analysis. SAMA enables a rapid, exhaustive and quantitative 3D analysis of the shape of a population of structures in a 3D image. SAMA is cross-platform, licensed under the GPLv3 and available at http://montevil.theobio.org/content/sama.

Highlights

  • The past couple of decades have witnessed great progress in optical imaging, computational analysis and modeling of biological systems

  • In the past five years, 3D tissue culture models have greatly advanced our understanding of tissue morphogenesis and pathogenesis of several diseases, including cancer [5,6,7] by bridging the gap between complex whole animal models and simple 2D cell cultures that lack the architecture, geometry and functionality of the live glandular tissue

  • We introduce our open-source SAMA (Software for Automated Morphological Analysis) that takes into account various parameters that define a normal breast while using 3D simulations of breast morphogenesis

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Summary

Introduction

The past couple of decades have witnessed great progress in optical imaging, computational analysis and modeling of biological systems. In the quest for understanding development in higher organisms, biologists are seeking imaging modalities that are increasingly multidimensional by relying on cutting-edge computational approaches to monitor biological phenomena with exceptional resolution, specificity and dimensionality [1,2,3,4]. In the past five years, 3D tissue culture models have greatly advanced our understanding of tissue morphogenesis and pathogenesis of several diseases, including cancer [5,6,7] by bridging the gap between complex whole animal models and simple 2D cell cultures that lack the architecture, geometry and functionality of the live glandular tissue. A significant contribution of 3D cultures is towards understanding ductal and branching morphogenesis of epithelial cells.

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