Reconstructing human pancreatic islet architectures using computational optimization

Machine Learning Algorithms, Applied to Intact Islets of Langerhans, Demonstrate Significantly Enhanced Insulin Staining at the Capillary Interface of Human Pancreatic β Cells

“…To assess the spatial relationship of the β cells to the islet vasculature, the laminin images were added to the 2D images or 3D reconstructions (3c, purple). Whilst 3D computational modelling of islets has been performed previously [32,43], our data validate the modelling capacity of our approaches, which we then used in downstream applications.…”

“…We set out to develop a new automated approach to provide a more objective, timeefficient analysis that would allow the inclusion of the majority of β cells within the islet volumes imaged. Previous studies have used automated approaches to assess islet cell density and islet cell proportions (α and β cells) with islet 3D reconstructions [24,29,32,43]. Here, we aimed to create an automated model capable of identifying islet cells (insulinlabelled β cells) to then refine it for further downstream analyses to assess the subcellular distribution of key β cell proteins.…”

“…For example, many models have not been able to accurately capture the heterogeneity of cell sizes and shapes within an islet [30,31]. In other models, the presence of various islet structures including vasculature have not been considered [32].…”

Comparative analysis of reconstructed architectures from mice and human islets

“…Human and mouse islets were reconstructed using the iterative optimization algorithm described in detail in a previous work. 31 In short, the reconstruction algorithm consists of proposing an initial islet using the experimental nuclei coordinates as center coordinates of spherical cells with radii assigned randomly from reported experimental distributions. At each step of the iterative optimization algorithm, a cell is randomly selected and new center coordinates and radius are proposed for the selected cell.…”

“…Recently, a methodology based on computational optimization was proposed to reconstruct islet architectures from experimental data, 31 giving as a result islets composed of non-overlapping cells, also allowing to quantify cell-to-cell contacts within the islets. Based on this methodology, in this article we reconstruct architectures of both mouse and human islets in order to perform a structural comparison between species based on common structural characteristics such as cell-to-cell contacts and islet volumes, but also on connectivity related metrics derived from the analysis of reconstructed architectures using a network-based approach.…”