@inproceedings{JacomeEggelerPoethkowetal.2015, author = {J{\´a}come, Leonardo Agudo and Eggeler, Gunter and P{\"o}thkow, Kai and Paetsch, Olaf and Hege, Hans-Christian}, title = {Three-Dimensional Characterization of Superdislocation Interactions in the High Temperature and Low Stress Creep Regime of Ni-Base Superalloy Single Crystals}, booktitle = {Proceedings of CREEP 2015 - 13th International Conference on Creep and Fracture of Engineering Materials and Structures, May 31 - June 4, 2015, Toulouse, France}, pages = {16 -- 17}, year = {2015}, abstract = {Monocrystaline Ni-base superalloys are the material of choice for first row blades in jet engine gas turbines. Using a novel visualization tool for 3D reconstruction and visualization of dislocation line segments from stereo-pairs of scanning transmission electron microscopies, the superdislocation substructures in Ni-base superalloy LEK 94 (crept to ε = 26\%) are characterized. Probable scenarios are discussed, how these dislocation substructures form.}, language = {en} } @misc{BojarovskiHegeLieetal.2015, author = {Bojarovski, Stefan and Hege, Hans-Christian and Lie, Han Cheng and Weber, Marcus}, title = {Topological analysis and visualization of scalar functions characterizing conformational transitions of molecules on multiple time-scales}, journal = {Shape Up 2015 - Exercises in Materials Geometry and Topology, 14-18 Sept. 2015, Berlin, Germany}, year = {2015}, abstract = {Molecular processes such as protein folding or ligand-receptor-binding can be understood by analyzing the free energy landscape. Those processes are often metastable, i.e. the molecular systems remain in basins around local minima of the free energy landscape, and in rare cases undergo gauche transitions between metastable states by passing saddle-points of this landscape. By discretizing the configuration space, this can be modeled as a discrete Markov process. One way to compute the transition rates between conformations of a molecular system is by utilizing Transition Path Theory and the concept of committor functions. A fundamental problem from the computational point of view is that many time-scales are involved, ranging from 10^(-14) sec for the fastest motion to 10^(-6) sec or more for conformation changes that cause biological effects. The goal of our work is to provide a better understanding of such transitions in configuration space on various time-scales by analyzing characteristic scalar functions topologically and geometrically. We are developing suitable visualization and interaction techniques to support our analysis. For example, we are analyzing a transition rate indicator function by computing and visualizing its Reeb graph together with the sets of molecular states corresponding to maxima of the transition rate indicator function. A particular challenge is the high dimensionality of the domain which does not allow for a straightforward visualization of the function. The computational topology approach to the analysis of the transition rate indicator functions for a molecular system allows to explore different time scales of the system by utilizing coarser or finer topological partitioning of the function. A specific goal is the development of tools for analyzing the hierarchy of these partitionings. This approach tackles the analysis of a complex and sparse dataset from a different angle than the well-known spectral analysis of Markov State Models.}, language = {en} } @article{HermannPohlTremblayetal.2016, author = {Hermann, Gunter and Pohl, Vincent and Tremblay, Jean Christophe and Paulus, Beate and Hege, Hans-Christian and Schild, Axel}, title = {ORBKIT - A modular Python toolbox for cross-platform post-processing of quantum chemical wavefunction data}, volume = {37}, journal = {Journal of Computational Chemistry}, number = {16}, doi = {10.1002/jcc.24358}, pages = {1511 -- 1520}, year = {2016}, abstract = {ORBKIT is a toolbox for postprocessing electronic structure calculations based on a highly modular and portable Python architecture. The program allows computing a multitude of electronic properties of molecular systems on arbitrary spatial grids from the basis set representation of its electronic wave function, as well as several grid-independent properties. The required data can be extracted directly from the standard output of a large number of quantum chemistry programs. ORBKIT can be used as a standalone program to determine standard quantities, for example, the electron density, molecular orbitals, and derivatives thereof. The cornerstone of ORBKIT is its modular structure. The existing basic functions can be arranged in an individual way and can be easily extended by user-written modules to determine any other derived quantity. ORBKIT offers multiple output formats that can be processed by common visualization tools (VMD, Molden, etc.). Additionally, ORBKIT offers routines to order molecular orbitals computed at different nuclear configurations according to their electronic character and to interpolate the wavefunction between these configurations. The program is open-source under GNU-LGPLv3 license and freely available at https://github.com/orbkit/orbkit/. This article provides an overview of ORBKIT with particular focus on its capabilities and applicability, and includes several example calculations.}, language = {en} } @article{GoubergritsOsmanMevertetal.2016, author = {Goubergrits, Leonid and Osman, Jan and Mevert, Ricardo and Kertzscher, Ulrich and P{\"o}thkow, Kai and Hege, Hans-Christian}, title = {Turbulence in blood damage modeling}, volume = {39}, journal = {The International Journal of Artificial Organs}, number = {4}, doi = {10.5301/ijao.5000476}, pages = {147 -- 210}, year = {2016}, abstract = {Purpose: To account for the impact of turbulence in blood damage modeling, a novel approach based on the generation of instantaneous flow fields from RANS simulations is proposed. Methods: Turbulent flow in a bileaflet mechanical heart valve was simulated using RANS-based (SST k-ω) flow solver using FLUENT 14.5. The calculated Reynolds shear stress (RSS) field is transformed into a set of divergence-free random vector fields representing turbulent velocity fluctuations using procedural noise functions. To consider the random path of the blood cells, instantaneous flow fields were computed for each time step by summation of RSS-based divergence-free random and mean velocity fields. Using those instantaneous flow fields, instantaneous pathlines and corresponding point-wise instantaneous shear stresses were calculated. For a comparison, averaged pathlines based on mean velocity field and respective viscous shear stresses together with RSS values were calculated. Finally, the blood damage index (hemolysis) was integrated along the averaged and instantaneous pathlines using a power law approach and then compared. Results: Using RSS in blood damage modeling without a correction factor overestimates damaging stress and thus the blood damage (hemolysis). Blood damage histograms based on both presented approaches differ. Conclusions: A novel approach to calculate blood damage without using RSS as a damaging parameter is established. The results of our numerical experiment support the hypothesis that the use of RSS as a damaging parameter should be avoided.}, language = {en} } @article{WilliePapPerkaetal.2015, author = {Willie, Bettina M. and Pap, Thomas and Perka, Carsten and Schmidt, Carsten Oliver and Eckstein, Felix and Arampatzis, Adamantios and Hege, Hans-Christian and Madry, Henning and Vortkamp, Andrea and Duda, Georg}, title = {OVERLOAD - Rolle der Gelenk{\"u}berlastung in der prim{\"a}ren Arthrose - Die Krankheitsprogression verstehen und vermeiden}, volume = {74}, journal = {Zeitschrift f{\"u}r Rheumatologie}, doi = {10.1007/s00393-014-1561-2}, pages = {618 -- 621}, year = {2015}, abstract = {Intakte Gelenke sind eine Voraussetzung f{\"u}r das Funktionieren des Skeletts und die Mobilit{\"a}t im Lebensalltag. Ein gesunder Bewegungsapparat ist die Grundlage f{\"u}r die Funktionsf{\"a}higkeit des Herz-Kreislauf-Systems wie auch der Immunabwehr. Bewegungs- und Physiotherapie sowie verschiedene Formen der Patientenaktivit{\"a}t stellen essenzielle klinische Ans{\"a}tze in der Behandlung von neurodegenerativen Erkrankungen, Schlaganfall, Diabetes und Krebs dar. Kommt es zu degenerativen Ver{\"a}nderungen von Gelenken, bedeutet dies eine wesentliche Beeintr{\"a}chtigung der Mobilit{\"a}t. N{\"a}chtliche Schmerzen und Schlafst{\"o}rungen treten in fortgeschrittenen Stadien auf und sind besonders belastend. Arthrose wird auch als degenerative Gelenkerkrankung bezeichnet. Sie geht mit Ver{\"a}nderungen in der Struktur und Zusammensetzung des Gelenkknorpels wie auch des verkalkten Knorpels, der subchondralen Kortikalis, der subchondralen Spongiosa, des Meniskus, der Gelenkkapsel und der Synovialis einher, was schließlich zur Degeneration dieser Gewebe f{\"u}hrt, aus denen sich die Synovialgelenke zusammensetzen.}, language = {de} } @misc{SieberKuhnHegeetal.2015, author = {Sieber, Moritz and Kuhn, Alexander and Hege, Hans-Christian and Paschereit, C. Oliver and Oberleithner, Kilian}, title = {A Graphical Representation of the Spectral Proper Orthogonal Decomposition}, journal = {68th Annual Meeting of the APS Division of Fluid Dynamics, Gallery of Fluid Motion, Nov 22-24, 2015, Boston, MA, USA.}, year = {2015}, abstract = {We consider the spectral proper orthogonal decomposition (SPOD) for experimental data of a turbulent swirling jet. This newly introduced method combines the advantages of spectral methods, such as Fourier decomposition or dynamic mode decomposition, with the energy-ranked proper orthogonal decomposition (POD). This poster visualizes how the modal energy spectrum transitions from the spectral purity of Fourier space to the sparsity of POD space. The transition is achieved by changing a single parameter - the width of the SPOD filter. Each dot in the 3D space corresponds to an SPOD mode pair, where the size and color indicates its spectral coherence. What we notice is that neither the Fourier nor the POD spectrum achieves a clear separation of the dynamic phenomena. Scanning through the graph from the front plane (Fourier) to the back plane (POD), we observe how three highly coherent SPOD modes emerge from the dispersed Fourier spectrum and later branch out into numerous POD modes. The spatial properties of these three individual SPOD modes are displayed in the back of the graph using line integral convolution colored by vorticity. The first two modes correspond to single-helical global instabilities that are well known for these flows. Their coexistence, however, has not been observed until now. The third mode is of double- helical shape and has not been observed so far. For this considered data set and many others, the SPOD is superior in identification of coherent structures in turbulent flows. Hopefully, it gives access to new fluid dynamic phenomena and enriches the available methods.}, language = {en} } @misc{KramerNoackBaumetal.2017, author = {Kramer, Tobias and Noack, Matthias and Baum, Daniel and Hege, Hans-Christian and Heller, Eric J.}, title = {Dust and gas emission from cometary nuclei: the case of comet 67P/Churyumov-Gerasimenko}, issn = {1438-0064}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-66338}, year = {2017}, abstract = {Comets display with decreasing solar distance an increased emission of gas and dust particles, leading to the formation of the coma and tail. Spacecraft missions provide insight in the temporal and spatial variations of the dust and gas sources located on the cometary nucleus. For the case of comet 67P/Churyumov-Gerasimenko (67P/C-G), the long-term obser- vations from the Rosetta mission point to a homogeneous dust emission across the entire illuminated surface. Despite the homogeneous initial dis- tribution, a collimation in jet-like structures becomes visible. We propose that this observation is linked directly to the complex shape of the nucleus and projects concave topographical features into the dust coma. To test this hypothesis, we put forward a gas-dust description of 67P/C-G, where gravitational and gas forces are accurately determined from the surface mesh and the rotation of the nucleus is fully incorporated. The emerging jet-like structures persist for a wide range of gas-dust interactions and show a dust velocity dependent bending.}, language = {en} } @misc{StallingSeebassZoeckleretal.2000, author = {Stalling, Detlev and Seebass, Martin and Z{\"o}ckler, Malte and Hege, Hans-Christian}, title = {Hyperthermia Treatment Planning with HyperPlan - User's Manual}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-5957}, number = {00-27}, year = {2000}, abstract = {HyperPlan is a software system for performing 3D-simulations and treatment planning in regional hyperthermia. It allows the user to understand the complex effects of electromagnetic wave propagation and heat transport inside a patient's body. Optimized power amplitudes and phase settings can be calculated for the BSD radiowave applicators Sigma 60 and Sigma 2000 (eye-applicator). HyperPlan is built on top of the modular, object-oriented visualization system Amira. This system already contains powerful algorithms for image processing, geometric modelling and 3D graphics display. HyperPlan provides a number of hyperthermia-specific modules, allowing the user to create 3D tetrahedral patient models suitable for treatment planning. In addition, all numerical simulation modules required for hyperthermia simulation are part of HyperPlan. This guide provides a step-by-step introduction to hyperthermia planning using HyperPlan. It also describes the usage of the underlying visualization system Amira.}, language = {en} } @misc{HegeMerzkyZachow2000, author = {Hege, Hans-Christian and Merzky, Andre and Zachow, Stefan}, title = {Distributed Visualization with OpenGL Vizserver: Practical Experiences}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-5992}, number = {00-31}, year = {2000}, abstract = {The increasing demand for distributed solutions in computing technology does not stop when it comes to visualization techniques. However, the capabilities of todays applications to perform remote rendering are limited by historical design legacys. Especially the popular X11 protokoll, which has been proven to be extremely flexible and usefull for remote 2D graphics applications, breaks down for the case of remote 3D rendering. In this white paper, we give a short overview of generic remote rendering technologies available today, and compare their performance to the recently released vizserver by SGI: a network extension to the SGI OpenGL rendering engines.}, language = {en} } @misc{KaehlerSimonHege2001, author = {K{\"a}hler, Ralf and Simon, Mark and Hege, Hans-Christian}, title = {Fast Volume Rendering of Sparse High-Resolution Datasets Using Adaptive Mesh Refinement Hierarchies}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-6516}, number = {01-25}, year = {2001}, abstract = {In this paper we present an algorithm that accelerates 3D texture-based volume rendering of large and sparse data sets. A hierarchical data structure (known as AMR tree) consisting of nested uniform grids is employed in order to efficiently encode regions of interest. The hierarchies resulting from this kind of space partitioning yield a good balance between the amount of volume to render and the number of texture bricks -- a prerequisite for fast rendering. Comparing our approach to an octree based algorithm we show that our algorithm increases rendering performance significantly for sparse data. A further advantage is that less parameter tuning is necessary.}, language = {en} } @misc{KaehlerHege2001, author = {K{\"a}hler, Ralf and Hege, Hans-Christian}, title = {Interactive Volume Rendering of Adaptive Mesh Refinement Data}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-6561}, number = {01-30}, year = {2001}, abstract = {Many phenomena in nature and engineering happen simultaneously on rather diverse spatial and temporal scales, i.e.\ exhibit a multi-scale character. Therefore various hierarchical data structures and numerical schemes have been devised to represent quantitatively such phenomena. A special numerical multilevel technique, associated with a particular hierarchical data structure, is so-called Adaptive Mesh Refinement (AMR). This scheme achieves locally very high spatial and temporal resolutions. Due to its popularity, many scientists are in need of interactive visualization tools for AMR data. In this article we present a 3D texture-based volume rendering algorithm for AMR data, that directly utilizes the hierarchical structure. Thereby interactive rendering even for large data sets is achieved. In particular the problems of interpolation artifacts, opacity corrections, and texture memory limitations are addressed. The algorithm's value in practice is demonstrated with simulation and image data.}, language = {en} } @misc{ZoecklerReinBrandtetal.2001, author = {Z{\"o}ckler, Malte and Rein, Karlheinz and Brandt, Robert and Stalling, Detlev and Hege, Hans-Christian}, title = {Creating Virtual Insect Brains with Amira}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-6589}, number = {01-32}, year = {2001}, abstract = {By combining techniques of preparation, histology, confocal microscopy, data visualization and data processing, we have created and recently published a standard brain model for drosophila and honey bee brains. This report describes the algorithms and implementation of the corresponding software modules. At the same time it serves as a user's guide for scientist who want to reproduce the results for differerent species or mutants.}, language = {en} } @misc{ZachowZilskeHege2007, author = {Zachow, Stefan and Zilske, Michael and Hege, Hans-Christian}, title = {3D reconstruction of individual anatomy from medical image data: Segmentation and geometry processing}, issn = {1438-0064}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-10440}, number = {07-41}, year = {2007}, abstract = {For medical diagnosis, visualization, and model-based therapy planning three-dimensional geometric reconstructions of individual anatomical structures are often indispensable. Computer-assisted, model-based planning procedures typically cover specific modifications of "virtual anatomy" as well as numeric simulations of associated phenomena, like e.g. mechanical loads, fluid dynamics, or diffusion processes, in order to evaluate a potential therapeutic outcome. Since internal anatomical structures cannot be measured optically or mechanically in vivo, three-dimensional reconstruction of tomographic image data remains the method of choice. In this work the process chain of individual anatomy reconstruction is described which consists of segmentation of medical image data, geometrical reconstruction of all relevant tissue interfaces, up to the generation of geometric approximations (boundary surfaces and volumetric meshes) of three-dimensional anatomy being suited for finite element analysis. All results presented herein are generated with amira ® - a highly interactive software system for 3D data analysis, visualization and geometry reconstruction.}, language = {en} } @misc{DeuflhardHege2005, author = {Deuflhard, Peter and Hege, Hans-Christian}, title = {Die Vision einer individuellen quantitativen Medizin}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-8805}, number = {05-47}, year = {2005}, abstract = {Die Autoren schreiben dieses Papier aus der eingeschr{\"a}nkten Sicht der Mathematik und der Informationstechnik. Um den speziellen Beitrag dieser Disziplinen {\"u}berhaupt diskutieren zu k{\"o}nnen, sehen wir uns jedoch gezwungen, einen Rahmen abzustecken, den wir f{\"u}r das Jahr 2020 vorhersehen -- nach Wahrscheinlichkeit und aus unserem engeren fachlichen Blickwinkel. Vorab bitten wir schon einmal bei den medizinischen Fachleuten um Nachsicht, wenn wir uns in ihrem Revier allzu dillettantisch bewegen. Vielleicht f{\"o}rdert aber auch unser eingeschr{\"a}nkter Blickwinkel ansonsten unbedachte Aspekte zutage -- das hoffen wir zumindest.}, language = {de} } @inproceedings{HanikHegevonTycowicz2022, author = {Hanik, Martin and Hege, Hans-Christian and von Tycowicz, Christoph}, title = {A Nonlinear Hierarchical Model for Longitudinal Data on Manifolds}, booktitle = {2022 IEEE 19th International Symposium on Biomedical Imaging (ISBI)}, arxiv = {http://arxiv.org/abs/2202.01180}, doi = {10.1109/ISBI52829.2022.9761465}, pages = {1 -- 5}, year = {2022}, abstract = {Large longitudinal studies provide lots of valuable information, especially in medical applications. A problem which must be taken care of in order to utilize their full potential is that of correlation between intra-subject measurements taken at different times. For data in Euclidean space this can be done with hierarchical models, that is, models that consider intra-subject and between-subject variability in two different stages. Nevertheless, data from medical studies often takes values in nonlinear manifolds. Here, as a first step, geodesic hierarchical models have been developed that generalize the linear ansatz by assuming that time-induced intra-subject variations occur along a generalized straight line in the manifold. However, this is often not the case (e.g., periodic motion or processes with saturation). We propose a hierarchical model for manifold-valued data that extends this to include trends along higher-order curves, namely B{\´e}zier splines in the manifold. To this end, we present a principled way of comparing shape trends in terms of a functional-based Riemannian metric. Remarkably, this metric allows efficient, yet simple computations by virtue of a variational time discretization requiring only the solution of regression problems. We validate our model on longitudinal data from the osteoarthritis initiative, including classification of disease progression.}, language = {en} } @inproceedings{HarthBastTroidletal.2023, author = {Harth, Philipp and Bast, Arco and Troidl, Jakob and Meulemeester, Bjorge and Pfister, Hanspeter and Beyer, Johanna and Oberlaender, Marcel and Hege, Hans-Christian and Baum, Daniel}, title = {Rapid Prototyping for Coordinated Views of Multi-scale Spatial and Abstract Data: A Grammar-based Approach}, booktitle = {Eurographics Workshop on Visual Computing for Biology and Medicine (VCBM)}, doi = {10.2312/vcbm.20231218}, year = {2023}, abstract = {Visualization grammars are gaining popularity as they allow visualization specialists and experienced users to quickly create static and interactive views. Existing grammars, however, mostly focus on abstract views, ignoring three-dimensional (3D) views, which are very important in fields such as natural sciences. We propose a generalized interaction grammar for the problem of coordinating heterogeneous view types, such as standard charts (e.g., based on Vega-Lite) and 3D anatomical views. An important aspect of our web-based framework is that user interactions with data items at various levels of detail can be systematically integrated and used to control the overall layout of the application workspace. With the help of a concise JSON-based specification of the intended workflow, we can handle complex interactive visual analysis scenarios. This enables rapid prototyping and iterative refinement of the visual analysis tool in collaboration with domain experts. We illustrate the usefulness of our framework in two real-world case studies from the field of neuroscience. Since the logic of the presented grammar-based approach for handling interactions between heterogeneous web-based views is free of any application specifics, it can also serve as a template for applications beyond biological research.}, language = {en} } @article{VohraHerreraTavhelidseSucketal.2024, author = {Vohra, Sumit Kumar and Herrera, Kristian and Tavhelidse-Suck, Tinatini and Knoblich, Simon and Seleit, Ali and Boulanger-Weill, Jonathan and Chambule, Sydney and Aspiras, Ariel and Santoriello, Cristina and Randlett, Owen and Wittbrodt, Joachim and Aulehla, Alexander and Lichtman, Jeff W. and Fishman, Mark and Hege, Hans-Christian and Baum, Daniel and Engert, Florian and Isoe, Yasuko}, title = {Multi-species community platform for comparative neuroscience in teleost fish}, journal = {bioRxiv}, doi = {10.1101/2024.02.14.580400}, year = {2024}, abstract = {Studying neural mechanisms in complementary model organisms from different ecological niches in the same animal class can leverage the comparative brain analysis at the cellular level. To advance such a direction, we developed a unified brain atlas platform and specialized tools that allowed us to quantitatively compare neural structures in two teleost larvae, medaka (Oryzias latipes) and zebrafish (Danio rerio). Leveraging this quantitative approach we found that most brain regions are similar but some subpopulations are unique in each species. Specifically, we confirmed the existence of a clear dorsal pallial region in the telencephalon in medaka lacking in zebrafish. Further, our approach allows for extraction of differentially expressed genes in both species, and for quantitative comparison of neural activity at cellular resolution. The web-based and interactive nature of this atlas platform will facilitate the teleost community's research and its easy extensibility will encourage contributions to its continuous expansion.}, language = {en} } @article{HarthUdvaryBoeltsetal.2024, author = {Harth, Philipp and Udvary, Daniel and Boelts, Jan and Baum, Daniel and Macke, Jakob H. and Hege, Hans-Christian and Oberlaender, Marcel}, title = {Dissecting origins of wiring specificity in dense cortical connectomes}, journal = {bioRxiv}, doi = {10.1101/2024.12.14.628490}, year = {2024}, abstract = {Wiring specificity in the cortex is observed across scales from the subcellular to the network level. It describes the deviations of connectivity patterns from those expected in randomly connected networks. Understanding the origins of wiring specificity in neural networks remains difficult as a variety of generative mechanisms could have contributed to the observed connectome. To take a step forward, we propose a generative modeling framework that operates directly on dense connectome data as provided by saturated reconstructions of neural tissue. The computational framework allows testing different assumptions of synaptic specificity while accounting for anatomical constraints posed by neuron morphology, which is a known confounding source of wiring specificity. We evaluated the framework on dense reconstructions of the mouse visual and the human temporal cortex. Our template model incorporates assumptions of synaptic specificity based on cell type, single-cell identity, and subcellular compartment. Combinations of these assumptions were sufficient to model various connectivity patterns that are indicative of wiring specificity. Moreover, the identified synaptic specificity parameters showed interesting similarities between both datasets, motivating further analysis of wiring specificity across species.}, language = {en} } @misc{NavaYazdaniHegevonTycowicz2021, author = {Nava-Yazdani, Esfandiar and Hege, Hans-Christian and von Tycowicz, Christoph}, title = {A Hierarchical Geodesic Model for Longitudinal Analysis on Manifolds}, issn = {1438-0064}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-85187}, year = {2021}, abstract = {In many applications, geodesic hierarchical models are adequate for the study of temporal observations. We employ such a model derived for manifold-valued data to Kendall's shape space. In particular, instead of the Sasaki metric, we adapt a functional-based metric, which increases the computational efficiency and does not require the implementation of the curvature tensor. We propose the corresponding variational time discretization of geodesics and employ the approach for longitudinal analysis of 2D rat skulls shapes as well as 3D shapes derived from an imaging study on osteoarthritis. Particularly, we perform hypothesis test and estimate the mean trends.}, language = {en} } @article{BoeltsHarthGaoetal.2023, author = {Boelts, Jan and Harth, Philipp and Gao, Richard and Udvary, Daniel and Yanez, Felipe and Baum, Daniel and Hege, Hans-Christian and Oberlaender, Marcel and Macke, Jakob H.}, title = {Simulation-based inference for efficient identification of generative models in computational connectomics}, volume = {19}, journal = {PLOS Computational Biology}, number = {9}, doi = {10.1371/journal.pcbi.1011406}, year = {2023}, abstract = {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.}, language = {en} }