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Recent advances in connectomics research enable the acquisition of increasing amounts of data about the connectivity patterns of neurons. How can we use this wealth of data to efficiently derive and test hypotheses about the principles underlying these patterns? A common approach is to simulate neuronal networks using a hypothesized wiring rule in a generative model and to compare the resulting synthetic data with empirical data. However, most wiring rules have at least some free parameters, and identifying parameters that reproduce empirical data can be challenging as it often requires manual parameter tuning. Here, we propose to use simulation-based Bayesian inference (SBI) to address this challenge. Rather than optimizing a fixed wiring rule to fit the empirical data, SBI considers many parametrizations of a rule and performs Bayesian inference to identify the parameters that are compatible with the data. It uses simulated data from multiple candidate wiring rule parameters and relies on machine learning methods to estimate a probability distribution (the 'posterior distribution over parameters conditioned on the data') that characterizes all data-compatible parameters. We demonstrate how to apply SBI in computational connectomics by inferring the parameters of wiring rules in an in silico model of the rat barrel cortex, given in vivo connectivity measurements. SBI identifies a wide range of wiring rule parameters that reproduce the measurements. We show how access to the posterior distribution over all data-compatible parameters allows us to analyze their relationship, revealing biologically plausible parameter interactions and enabling experimentally testable predictions. We further show how SBI can be applied to wiring rules at different spatial scales to quantitatively rule out invalid wiring hypotheses. Our approach is applicable to a wide range of generative models used in connectomics, providing a quantitative and efficient way to constrain model parameters with empirical connectivity data.
Recent advances in connectomics research enable the acquisition of increasing amounts of data about the connectivity patterns of neurons. How can we use this wealth of data to efficiently derive and test hypotheses about the principles underlying these patterns? A common approach is to simulate neural networks using a hypothesized wiring rule in a generative model and to compare the resulting synthetic data with empirical data. However, most wiring rules have at least some free parameters and identifying parameters that reproduce empirical data can be challenging as it often requires manual parameter tuning. Here, we propose to use simulation-based Bayesian inference (SBI) to address this challenge. Rather than optimizing a single rule to fit the empirical data, SBI considers many parametrizations of a wiring rule and performs Bayesian inference to identify the parameters that are compatible with the data. It uses simulated data from multiple candidate wiring rules and relies on machine learning methods to estimate a probability distribution (the `posterior distribution over rule parameters conditioned on the data') that characterizes all data-compatible rules. We demonstrate how to apply SBI in connectomics by inferring the parameters of wiring rules in an in silico model of the rat barrel cortex, given in vivo connectivity measurements. SBI identifies a wide range of wiring rule parameters that reproduce the measurements. We show how access to the posterior distribution over all data-compatible parameters allows us to analyze their relationship, revealing biologically plausible parameter interactions and enabling experimentally testable predictions. We further show how SBI can be applied to wiring rules at different spatial scales to quantitatively rule out invalid wiring hypotheses. Our approach is applicable to a wide range of generative models used in connectomics, providing a quantitative and efficient way to constrain model parameters with empirical connectivity data.
The remarkably complex skeletal systems of the sea stars (Echinodermata, Asteroidea), consisting of hundreds to thousands of individual elements (ossicles), have intrigued investigators for more than 150 years. While the general features and structural diversity of isolated asteroid ossicles have been well documented in the literature, the task of mapping the spatial organization of these constituent skeletal elements in a whole-animal context represents an incredibly laborious process, and as such, has remained largely unexplored.
To address this unmet need, particularly in the context of understanding structure-function relationships in these complex skeletal systems, we present an integrated approach that combines micro-computed tomography, semi-automated ossicle segmentation, data visualization tools, and the production of additively manufactured tangible models to reveal biologically relevant structural data that can be rapidly analyzed in an intuitive manner.
In the present study, we demonstrate this high-throughput workflow by segmenting and analyzing entire skeletal systems of the giant knobby star, Pisaster giganteus, at four different stages of growth. The in-depth analysis, presented herein, provides a fundamental understanding of the three-dimensional skeletal architecture of the sea star body wall, the process of skeletal maturation during growth, and the relationship between skeletal organization and morphological characteristics of individual ossicles.
The widespread implementation of this approach for investigating other species, subspecies, and growth series has the potential to fundamentally improve our understanding of asteroid skeletal architecture and biodiversity in relation to mobility, feeding habits, and environmental specialization in this fascinating group of echinoderms.
Data are often subject to some degree of uncertainty, whether aleatory or epistemic. This applies both to experimental data acquired with sensors as well as to simulation data. Displaying these data and their uncertainty faithfully is crucial for gaining knowledge. Specifically, the effective communication of the uncertainty can influence the interpretation of the data and the user’s trust in the visualization. However, uncertainty-aware visualization has gotten little attention in molecular visualization. When using the established molecular representations, the physicochemical attributes of the molecular data usually already occupy the common visual channels like shape, size, and color. Consequently, to encode uncertainty information, we need to open up another channel by using feature lines. Even though various line variables have been proposed for uncertainty visualizations, they have so far been primarily used for two-dimensional data and there has been little perceptual evaluation. Thus, we conducted two perceptual studies to determine the suitability of the line variables blur, dashing, grayscale, sketchiness, and width for distinguishing several values in molecular visualizations. While our work was motivated by uncertainty visualization, our techniques and study results also apply to other types of scalar data.
Ridge surfaces represent important features for the analysis of 3-dimensional (3D) datasets in diverse applications and are often derived from varying underlying data including flow fields, geological fault data, and point data, but they can also be present in the original scalar images acquired using a plethora of imaging techniques. Our work is motivated by the analysis of image data acquired using micro-computed tomography (μCT) of ancient, rolled and folded thin-layer structures such as papyrus, parchment, and paper as well as silver and lead sheets. From these documents we know that they are 2-dimensional (2D) in nature. Hence, we are particularly interested in reconstructing 2D manifolds that approximate the document’s structure. The image data from which we want to reconstruct the 2D manifolds are often very noisy and represent folded, densely-layered structures with many artifacts, such as ruptures or layer splitting and merging. Previous ridge-surface extraction methods fail to extract the desired 2D manifold for such challenging data. We have therefore developed a novel method to extract 2D manifolds. The proposed method uses a local fast marching scheme in combination with a separation of the region covered by fast marching into two sub-regions. The 2D manifold of interest is then extracted as the surface separating the two sub-regions. The local scheme can be applied for both automatic propagation as well as interactive analysis. We demonstrate the applicability and robustness of our method on both artificial data as well as real-world data including folded silver and papyrus sheets.
Tooth enamel is the hardest tissue in human organism, formed by prism layers in regularly alternating directions. These prisms form the Hunter-Schreger Bands (HSB) pattern when under side illumination, which is composed of light and dark stripes resembling fingerprints. We have shown in previous works that HSB pattern is highly variable, seems to be unique for each tooth and can be used as a biometric method for human identification. Since this pattern cannot be acquired with sensors, the HSB region in the digital photograph must be identified and correctly segmented from the rest of the tooth and background. Although these areas can be manually removed, this process is not reliable as excluded areas can vary according to the individual‘s subjective impression. Therefore, the aim of this work was to develop an algorithm that automatically selects the region of interest (ROI), thus, making the entire biometric process straightforward. We used two different approaches: a classical image processing method which we called anisotropy-based segmentation (ABS) and a machine learning method known as U-Net, a fully convolutional neural network. Both approaches were applied to a set of extracted tooth images. U-Net with some post processing outperformed ABS in the segmentation task with an Intersection Over Union (IOU) of 0.837 against 0.766. Even with a small dataset, U-Net proved to be a potential candidate for fully automated in-mouth application. However, the ABS technique has several parameters which allow a more flexible segmentation with interactive adjustments specific to image properties.
Three-dimensional (3D) imaging, such as micro-computed tomography (micro-CT), is increasingly being used by organismal biologists for precise and comprehensive anatomical characterization. However, the segmentation of anatomical structures remains a bottleneck in research, often requiring tedious manual work. Here, we propose a pipeline for the fully-automated segmentation of anatomical structures in micro-CT images utilizing state-of-the-art deep learning methods, selecting the ant brain as a test case. We implemented the U-Net architecture for 2D image segmentation for our convolutional neural network (CNN), combined with pixel-island detection. For training and validation of the network, we assembled a dataset of semi-manually segmented brain images of 76 ant species. The trained network predicted the brain area in ant images fast and accurately; its performance tested on validation sets showed good agreement between the prediction and the target, scoring 80% Intersection over Union
(IoU) and 90% Dice Coefficient (F1) accuracy. While manual segmentation usually takes many hours for each brain, the trained network takes only a few minutes. Furthermore, our network is generalizable for segmenting the whole neural system in full-body scans, and works in tests on distantly related and morphologically divergent insects (e.g., fruit flies). The latter suggests that methods like the one presented here generally apply across diverse taxa. Our method makes the construction of segmented maps and the morphological quantification of different species more efficient and scalable to large datasets, a step toward a big data approach to organismal anatomy.
The elephant trunk operates as a muscular hydrostat and is actuated by the most complex musculature known in animals. Because the number of trunk muscles is unclear, we performed dense reconstructions of trunk muscle fascicles, elementary muscle units, from microCT scans of an Asian baby elephant trunk. Muscle architecture changes markedly across the trunk. Trunk tip and finger consist of about 8,000 extraordinarily filigree fascicles. The dexterous finger consists exclusively of microscopic radial fascicles pointing to a role of muscle miniaturization in elephant dexterity. Radial fascicles also predominate (at 82% volume) the remainder of the trunk tip and we wonder if radial muscle fascicles are of particular significance for fine motor control of the dexterous trunk tip. By volume, trunk-shaft muscles comprise one-third of the numerous, small radial muscle fascicles, two-thirds of the three subtypes of large longitudinal fascicles (dorsal longitudinals, ventral outer obliques, and ventral inner obliques), and a small fraction of transversal fascicles. Shaft musculature is laterally, but not radially, symmetric. A predominance of dorsal over ventral radial muscles and of ventral over dorsal longitudinal muscles may result in a larger ability of the shaft to extend dorsally than ventrally and to bend inward rather than outward. There are around 90,000 trunk muscle fascicles. While primate hand control is based on fine control of contraction by the convergence of many motor neurons on a small set of relatively large muscles, evolution of elephant grasping has led to thousands of microscopic fascicles, which probably outnumber facial motor neurons.