@article{KlusNueskePeitzetal.2020, author = {Klus, Stefan and N{\"u}ske, Feliks and Peitz, Sebastian and Niemann, Jan-Hendrik and Clementi, Cecilia and Sch{\"u}tte, Christof}, title = {Data-driven approximation of the Koopman generator: Model reduction, system identification, and control}, volume = {406}, journal = {Physica D: Nonlinear Phenomena}, doi = {10.1016/j.physd.2020.132416}, year = {2020}, language = {en} } @article{ChaumelSchotteBizzarroetal.2020, author = {Chaumel, J{\´u}lia and Schotte, Merlind and Bizzarro, Joseph J. and Zaslansky, Paul and Fratzl, Peter and Baum, Daniel and Dean, Mason N.}, title = {Co-aligned chondrocytes: Zonal morphological variation and structured arrangement of cell lacunae in tessellated cartilage}, volume = {134}, journal = {Bone}, doi = {10.1016/j.bone.2020.115264}, pages = {115264}, year = {2020}, abstract = {In most vertebrates the embryonic cartilaginous skeleton is replaced by bone during development. During this process, cartilage cells (chondrocytes) mineralize the extracellular matrix and undergo apoptosis, giving way to bone cells (osteocytes). In contrast, sharks and rays (elasmobranchs) have cartilaginous skeletons throughout life, where only the surface mineralizes, forming a layer of tiles (tesserae). Elasmobranch chondrocytes, unlike those of other vertebrates, survive cartilage mineralization and are maintained alive in spaces (lacunae) within tesserae. However, the function(s) of the chondrocytes in the mineralized tissue remain unknown. Applying a custom analysis workflow to high-resolution synchrotron microCT scans of tesserae, we characterize the morphologies and arrangements of stingray chondrocyte lacunae, using lacunar morphology as a proxy for chondrocyte morphology. We show that the cell density is comparable in unmineralized and mineralized tissue from our study species and that cells maintain the similar volume even when they have been incorporated into tesserae. This discovery supports previous hypotheses that elasmobranch chondrocytes, unlike those of other taxa, do not proliferate, hypertrophy or undergo apoptosis during mineralization. Tessera lacunae show zonal variation in their shapes—being flatter further from and more spherical closer to the unmineralized cartilage matrix and larger in the center of tesserae— and show pronounced organization into parallel layers and strong orientation toward neighboring tesserae. Tesserae also exhibit local variation in lacunar density, with the density considerably higher near pores passing through the tesseral layer, suggesting pores and cells interact (e.g. that pores contain a nutrient source). We hypothesize that the different lacunar types reflect the stages of the tesserae formation process, while also representing local variation in tissue architecture and cell function. Lacunae are linked by small passages (canaliculi) in the matrix to form elongate series at the tesseral periphery and tight clusters in the center of tesserae, creating a rich connectivity among cells. The network arrangement and the shape variation of chondrocytes in tesserae indicate that cells may interact within and between tesserae and manage mineralization differently from chondrocytes in other vertebrates, perhaps performing analogous roles to osteocytes in bone.}, language = {en} } @article{SchotteChaumelDeanetal.2020, author = {Schotte, Merlind and Chaumel, J{\´u}lia and Dean, Mason N. and Baum, Daniel}, title = {Image analysis pipeline for segmentation of a biological porosity network, the lacuno-canalicular system in stingray tesserae}, volume = {7}, journal = {MethodsX}, doi = {10.1016/j.mex.2020.100905}, pages = {100905}, year = {2020}, abstract = {A prerequisite for many analysis tasks in modern comparative biology is the segmentation of 3-dimensional (3D) images of the specimens being investigated (e.g. from microCT data). Depending on the specific imaging technique that was used to acquire the images and on the image resolution, different segmentation tools will be required. While some standard tools exist that can often be applied for specific subtasks, building whole processing pipelines solely from standard tools is often difficult. Some tasks may even necessitate the implementation of manual interaction tools to achieve a quality that is sufficient for the subsequent analysis. In this work, we present a pipeline of segmentation tools that can be used for the semi-automatic segmentation and quantitative analysis of voids in tissue (i.e. internal structural porosity). We use this pipeline to analyze lacuno-canalicular networks in stingray tesserae from 3D images acquired with synchrotron microCT. * The first step of this processing pipeline, the segmentation of the tesserae, was performed using standard marker-based watershed segmentation. The efficient processing of the next two steps, that is, the segmentation of all lacunae spaces belonging to a specific tessera and the separation of these spaces into individual lacunae required modern, recently developed tools. * For proofreading, we developed a graph-based interactive method that allowed us to quickly split lacunae that were accidentally merged, and to merge lacunae that were wrongly split. * Finally, the tesserae and their corresponding lacunae were subdivided into anatomical regions of interest (structural wedges) using a semi- manual approach.}, language = {en} } @misc{MollenhauerSchusterKlusetal.2020, author = {Mollenhauer, Mattes and Schuster, Ingmar and Klus, Stefan and Sch{\"u}tte, Christof}, title = {Singular Value Decomposition of Operators on Reproducing Kernel Hilbert Spaces}, volume = {304}, journal = {Advances om Dynamics, Optimization and Computation. Series: Studies in Systems, Decision and Control. A volume dedicated to Michael Dellnitz on his 60th birthday}, editor = {Junge, Oliver and Sch{\"u}tze, O. and Froyland, Gary and Ober-Blobaum, S. and Padberg-Gehle, K.}, publisher = {Springer International}, isbn = {978-3-030-51264-4}, doi = {10.1007/978-3-030-51264-4_5}, pages = {109 -- 131}, year = {2020}, language = {en} } @article{RamsConrad2020, author = {Rams, Mona and Conrad, Tim}, title = {Dictionary Learning for transcriptomics data reveals type-specific gene modules in a multi-class setting}, volume = {62}, journal = {it - Information Technology}, number = {3-4}, publisher = {De Gruyter}, address = {Oldenbourg}, issn = {2196-7032}, doi = {https://doi.org/10.1515/itit-2019-0048}, year = {2020}, language = {en} } @article{RaySunkaraSchuetteetal.2020, author = {Ray, Sourav and Sunkara, Vikram and Sch{\"u}tte, Christof and Weber, Marcus}, title = {How to calculate pH-dependent binding rates for receptor-ligand systems based on thermodynamic simulations with different binding motifs}, volume = {46}, journal = {Molecular Simulation}, number = {18}, publisher = {Taylor and Francis}, doi = {10.1080/08927022.2020.1839660}, pages = {1443 -- 1452}, year = {2020}, abstract = {Molecular simulations of ligand-receptor interactions are a computational challenge, especially when their association- ('on'-rate) and dissociation- ('off'-rate) mechanisms are working on vastly differing timescales. One way of tackling this multiscale problem is to compute the free-energy landscapes, where molecular dynamics (MD) trajectories are used to only produce certain statistical ensembles. The approach allows for deriving the transition rates between energy states as a function of the height of the activation-energy barriers. In this article, we derive the association rates of the opioids fentanyl and N-(3-fluoro-1-phenethylpiperidin-4-yl)-N-phenyl propionamide (NFEPP) in a μ-opioid receptor by combining the free-energy landscape approach with the square-root-approximation method (SQRA), which is a particularly robust version of Markov modelling. The novelty of this work is that we derive the association rates as a function of the pH level using only an ensemble of MD simulations. We also verify our MD-derived insights by reproducing the in vitro study performed by the Stein Lab.}, language = {en} } @article{LindowBruenigDercksenetal.2020, author = {Lindow, Norbert and Br{\"u}nig, Florian and Dercksen, Vincent J. and Fabig, Gunar and Kiewisz, Robert and Redemann, Stefanie and M{\"u}ller-Reichert, Thomas and Prohaska, Steffen and Baum, Daniel}, title = {Semi-automatic stitching of filamentous structures in image stacks from serial-section electron tomography}, journal = {bioRxiv}, doi = {10.1101/2020.05.28.120899}, year = {2020}, abstract = {We present a software-assisted workflow for the alignment and matching of filamentous structures across a 3D stack of serial images. This is achieved by combining automatic methods, visual validation, and interactive correction. After an initial alignment, the user can continuously improve the result by interactively correcting landmarks or matches of filaments. Supported by a visual quality assessment of regions that have been already inspected, this allows a trade-off between quality and manual labor. The software tool was developed to investigate cell division by quantitative 3D analysis of microtubules (MTs) in both mitotic and meiotic spindles. For this, each spindle is cut into a series of semi-thick physical sections, of which electron tomograms are acquired. The serial tomograms are then stitched and non-rigidly aligned to allow tracing and connecting of MTs across tomogram boundaries. In practice, automatic stitching alone provides only an incomplete solution, because large physical distortions and a low signal-to-noise ratio often cause experimental difficulties. To derive 3D models of spindles despite the problems related to sample preparation and subsequent data collection, semi-automatic validation and correction is required to remove stitching mistakes. However, due to the large number of MTs in spindles (up to 30k) and their resulting dense spatial arrangement, a naive inspection of each MT is too time consuming. Furthermore, an interactive visualization of the full image stack is hampered by the size of the data (up to 100 GB). Here, we present a specialized, interactive, semi-automatic solution that considers all requirements for large-scale stitching of filamentous structures in serial-section image stacks. The key to our solution is a careful design of the visualization and interaction tools for each processing step to guarantee real-time response, and an optimized workflow that efficiently guides the user through datasets.}, language = {en} } @article{PimentelSzengelEhlkeetal.2020, author = {Pimentel, Pedro and Szengel, Angelika and Ehlke, Moritz and Lamecker, Hans and Zachow, Stefan and Estacio, Laura and Doenitz, Christian and Ramm, Heiko}, title = {Automated Virtual Reconstruction of Large Skull Defects using Statistical Shape Models and Generative Adversarial Networks}, volume = {12439}, journal = {Towards the Automatization of Cranial Implant Design in Cranioplasty}, editor = {Li, Jianning and Egger, Jan}, edition = {1}, publisher = {Springer International Publishing}, doi = {10.1007/978-3-030-64327-0_3}, pages = {16 -- 27}, year = {2020}, abstract = {We present an automated method for extrapolating missing regions in label data of the skull in an anatomically plausible manner. The ultimate goal is to design patient-speci� c cranial implants for correcting large, arbitrarily shaped defects of the skull that can, for example, result from trauma of the head. Our approach utilizes a 3D statistical shape model (SSM) of the skull and a 2D generative adversarial network (GAN) that is trained in an unsupervised fashion from samples of healthy patients alone. By � tting the SSM to given input labels containing the skull defect, a First approximation of the healthy state of the patient is obtained. The GAN is then applied to further correct and smooth the output of the SSM in an anatomically plausible manner. Finally, the defect region is extracted using morphological operations and subtraction between the extrapolated healthy state of the patient and the defective input labels. The method is trained and evaluated based on data from the MICCAI 2020 AutoImplant challenge. It produces state-of-the art results on regularly shaped cut-outs that were present in the training and testing data of the challenge. Furthermore, due to unsupervised nature of the approach, the method generalizes well to previously unseen defects of varying shapes that were only present in the hidden test dataset.}, language = {en} } @article{SekuboyinaBayatHusseinietal.2020, author = {Sekuboyina, Anjany and Bayat, Amirhossein and Husseini, Malek E. and L{\"o}ffler, Maximilian and Li, Hongwei and Tetteh, Giles and Kukačka, Jan and Payer, Christian and Štern, Darko and Urschler, Martin and Chen, Maodong and Cheng, Dalong and Lessmann, Nikolas and Hu, Yujin and Wang, Tianfu and Yang, Dong and Xu, Daguang and Ambellan, Felix and Amiranashvili, Tamaz and Ehlke, Moritz and Lamecker, Hans and Lehnert, Sebastian and Lirio, Marilia and de Olaguer, Nicol{\´a}s P{\´e}rez and Ramm, Heiko and Sahu, Manish and Tack, Alexander and Zachow, Stefan and Jiang, Tao and Ma, Xinjun and Angerman, Christoph and Wang, Xin and Wei, Qingyue and Brown, Kevin and Wolf, Matthias and Kirszenberg, Alexandre and Puybareau, {\´E}lodie and Valentinitsch, Alexander and Rempfler, Markus and Menze, Bj{\"o}rn H. and Kirschke, Jan S.}, title = {VerSe: A Vertebrae Labelling and Segmentation Benchmark for Multi-detector CT Images}, journal = {arXiv}, arxiv = {http://arxiv.org/abs/2001.09193}, year = {2020}, language = {en} } @article{MelnykMontavonKlusetal.2020, author = {Melnyk, Kateryna and Montavon, Gr{\`e}goire and Klus, Stefan and Conrad, Tim}, title = {Graph Kernel Koopman Embedding for Human Microbiome Analysis}, volume = {5}, journal = {Applied Network Science}, number = {96}, doi = {10.1007/s41109-020-00339-2}, year = {2020}, abstract = {More and more diseases have been found to be strongly correlated with disturbances in the microbiome constitution, e.g., obesity, diabetes, or some cancer types. Thanks to modern high-throughput omics technologies, it becomes possible to directly analyze human microbiome and its influence on the health status. Microbial communities are monitored over long periods of time and the associations between their members are explored. These relationships can be described by a time-evolving graph. In order to understand responses of the microbial community members to a distinct range of perturbations such as antibiotics exposure or diseases and general dynamical properties, the time-evolving graph of the human microbial communities has to be analyzed. This becomes especially challenging due to dozens of complex interactions among microbes and metastable dynamics. The key to solving this problem is the representation of the time-evolving graphs as fixed-length feature vectors preserving the original dynamics. We propose a method for learning the embedding of the time-evolving graph that is based on the spectral analysis of transfer operators and graph kernels. We demonstrate that our method can capture temporary changes in the time-evolving graph on both synthetic data and real-world data. Our experiments demonstrate the efficacy of the method. Furthermore, we show that our method can be applied to human microbiome data to study dynamic processes.}, language = {en} }