Designed especially for neurobiologists, FluoRender is an interactive tool for multi-channel fluorescence microscopy data visualization and analysis.
Deep brain stimulation
BrainStimulator is a set of networks that are used in SCIRun to perform simulations of brain stimulation such as transcranial direct current stimulation (tDCS) and magnetic transcranial stimulation (TMS).
Developing software tools for science has always been a central vision of the SCI Institute.

SCI Publications


N. Ramesh, T. Tasdizen. “Detection and segmentation in microscopy images,” In Computer Vision for Microscopy Image Analysis, Academic Press, pp. 43-71. 2021.
DOI: 10.1016/B978-0-12-814972-0.00003-5


The plethora of heterogeneous data generated using modern microscopy imaging techniques eliminates the possibility of manual image analysis for biologists. Consequently, reliable and robust computerized techniques are critical to analyze microscopy data. Detection problems in microscopy images focuses on accurately identifying the objects of interest in an image that can be used to investigate hypotheses about developmental or pathological processes and can be indicative of prognosis in patients. Detection is also considered to be the preliminary step for solving subsequent problems, such as segmentation and tracking for various biological applications. Segmentation of the desired structures and regions in microscopy images require pixel-level labels to uniquely identify the individual structures and regions with contours for morphological and physiological analysis. Distributions of features extracted from the segmented regions can be used to compare normal versus disease or normal versus wild-type populations. Segmentation can be considered as a precursor for solving classification, reconstruction, and tracking problems in microscopy images. In this chapter, we discuss how the field of microscopic image analysis has progressed over the years, starting with traditional approaches and then followed by the study of learning algorithms. Because there is a lot of variability in microscopy data, it is essential to study learning algorithms that can adapt to these changes. We focus on deep learning approaches with convolutional neural networks (CNNs), as well as hierarchical methods for segmentation and detection in optical and electron microscopy images. Limitation of training data is one of the significant problems; hence, we explore solutions to learn better models with minimal user annotations.

M. Rasouli, R. M. Kirby, H. Sundar. “A Compressed, Divide and Conquer Algorithm for Scalable Distributed Matrix-Matrix Multiplication,” In The International Conference on High Performance Computing in Asia-Pacific Region, pp. 110-119. 2021.


Matrix-matrix multiplication (GEMM) is a widely used linear algebra primitive common in scientific computing and data sciences. While several highly-tuned libraries and implementations exist, these typically target either sparse or dense matrices. The performance of these tuned implementations on unsupported types can be poor, and this is critical in cases where the structure of the computations is associated with varying degrees of sparsity. One such example is Algebraic Multigrid (AMG), a popular solver and preconditioner for large sparse linear systems. In this work, we present a new divide and conquer sparse GEMM, that is also highly performant and scalable when the matrix becomes dense, as in the case of AMG matrix hierarchies. In addition, we implement a lossless data compression method to reduce the communication cost. We combine this with an efficient communication pattern during distributed-memory GEMM to provide 2.24 times (on average) better performance than the state-of-the-art library PETSc. Additionally, we show that the performance and scalability of our method surpass PETSc even more when the density of the matrix increases. We demonstrate the efficacy of our methods by comparing our GEMM with PETSc on a wide range of matrices.

A. Rathore, N. Chalapathi, S. Palande, Bei Wang. “TopoAct: Visually Exploring the Shape of Activations in Deep Learning,” In Computer Graphics Forum, Vol. 40, No. 1, pp. 382-397. 2021.


Deep neural networks such as GoogLeNet, ResNet, and BERT have achieved impressive performance in tasks such as image and text classification. To understand how such performance is achieved, we probe a trained deep neural network by studying neuron activations, i.e., combinations of neuron firings, at various layers of the network in response to a particular input. With a large number of inputs, we aim to obtain a global view of what neurons detect by studying their activations. In particular, we develop visualizations that show the shape of the activation space, the organizational principle behind neuron activations, and the relationships of these activations within a layer. Applying tools from topological data analysis, we present TopoAct, a visual exploration system to study topological summaries of activation vectors. We present exploration scenarios using TopoAct that provide valuable insights into learned representations of neural networks. We expect TopoAct to give a topological perspective that enriches the current toolbox of neural network analysis, and to provide a basis for network architecture diagnosis and data anomaly detection.

A. Rauff, L.H. Timmins, R.T. Whitaker, J.A. Weiss. “A Nonparametric Approach for Estimating Three-Dimensional Fiber Orientation Distribution Functions (ODFs) in Fibrous Materials,” In IEEE Transactions on Medical Imaging, 2021.
DOI: 10.1109/TMI.2021.3115716


Many biological tissues contain an underlying fibrous microstructure that is optimized to suit a physiological function. The fiber architecture dictates physical characteristics such as stiffness, diffusivity, and electrical conduction. Abnormal deviations of fiber architecture are often associated with disease. Thus, it is useful to characterize fiber network organization from image data in order to better understand pathological mechanisms. We devised a method to quantify distributions of fiber orientations based on the Fourier transform and the Qball algorithm from diffusion MRI. The Fourier transform was used to decompose images into directional components, while the Qball algorithm efficiently converted the directional data from the frequency domain to the orientation domain. The representation in the orientation domain does not require any particular functional representation, and thus the method is nonparametric. The algorithm was verified to demonstrate its reliability and used on datasets from microscopy to show its applicability. This method increases the ability to extract information of microstructural fiber organization from experimental data that will enhance our understanding of structure-function relationships and enable accurate representation of material anisotropy in biological tissues.

M. Razi, M. Kirby, A. Narayan. “Kernel optimization for Low-Rank Multi-Fidelity Algorithms,” In International Journal for Uncertainty Quantification, Begel House Inc., pp. 31-54. 2021.


One of the major challenges for low-rank multi-fidelity (MF) approaches is the assumption that low-fidelity (LF) and high-fidelity (HF) models admit``similar''low-rank kernel representations. Low-rank MF methods have traditionally attempted to exploit low-rank representations of\emph linear kernels. However, such linear kernels may not be able to capture low-rank behavior, and they may admit LF and HF kernels that are not similar. Such a situation renders a naive approach to low-rank MF procedures ineffective. In this paper, we propose a novel approach for the selection of a near-optimal kernel function for use in low-rank MF methods. The proposed framework is a two-step strategy wherein:(1) hyperparameters of a library of kernel functions are optimized, and (2) a particular combination of of the optimized kernels is selected, through either a convex mixture (Additive Kernel Approach) or through a data-driven …

J. Salinet, R. Molero, F. S. Schlindwein, J. Karel, M. Rodrigo, J. L. Rojo-Álvarez, O. Berenfeld, A. M. Climent, B. Zenger, F. Vanheusden, J. G. S. Paredes, R. MacLeod, F. Atienza, M. S. Guillem, M. Cluitmans, P. Bonizzi. “Electrocardiographic imaging for atrial fibrillation: a perspective from computer models and animal experiments to clinical value,” In Frontiers in Physiology, Vol. 12, Frontiers Media, April, 2021.
DOI: 10.3389/fphys.2021.653013


Salinet et al. Electrocardiographic Imaging for Atrial Fibrillation treatment guidance (for example, localization of AF triggers and sustaining mechanisms), and we discuss the technological requirements and validation. We address experimental and clinical results, limitations, and future challenges for fruitful application of ECGI for AF understanding and management. We pay attention to existing techniques and clinical application, to computer models and (animal or human) experiments, to challenges of methodological and clinical validation. The overall objective of the study is to provide a consensus on valuable directions that ECGI research may take to provide future improvements in AF characterization and treatment guidance.

J. Sandhu, T. Bidone, R. D. Rabbitt. “Prestin Generates Instantaneous Force in Outer Hair Cell Membranes,” In Biophysical Journal, Vol. 120, No. 3, 2021.


Hearing occurs from sound reaching the inner ear cochlea, where electromotile Outer Hair Cells (OHCs) amplify vibrations by elongating and contracting rapidly in response to auditory frequency changes in membrane potential. OHCs can generate force cycle-by-cycle at frequencies exceeding 50kHz, but precisely how this is achieved is unclear. Electromotility requires expression of the transmembrane protein, prestin, which facilitates the electromechanical conversion through action of the Coulomb force acting on the anion Cl- bound at the core of the protein. However, recent experimental data suggests the charge displacement is too slow to support sound amplification at auditory frequencies. As a consequence, prestin electromechanics remain unclear at the molecular level. We hypothesize that prestin instantaneously transmits stress to the membrane, which subsequently drives charge displacement, membrane deformation, and OHC shape changes. To test the hypothesis, we examined the conformational dynamics of prestin and its effects on the motion of lipids under: (1) isometric conditions and (2) constant force conditions in order to mimic different regimes of membrane loading. All-atom molecular dynamics simulations of the prestin dimer embedded in POPC membranes were run and the trajectories analyzed. We discovered that under isometric conditions, the presence of a chloride ion in the electric field increased residue fluctuations. This trend was not observed under constant force conditions, supporting the idea that isometric conditions cause instantaneous force to be generated in the membrane. The analysis allowed us to identify the molecular mechanisms by which prestin allows electromechanical amplification by OHCs in the cochlea.

S. Sane, T. Athawale,, C.R. Johnson. “Visualization of Uncertain Multivariate Data via Feature Confidence Level-Sets,” In EuroVis 2021, 2021.

S. Sane, C.R. Johnson, H. Childs. “Investigating the Use of In Situ Reduction via Lagrangian Representations for Cosmology and Seismology Applications,” In ICCS 2021, 2021.

S. Sane, A. Yenpure, R. Bujack, M. Larsen, K. Moreland, C. Garth, C. R. Johnson,, H. Childs. “Scalable In Situ Computation of Lagrangian Representations via Local Flow Maps,” In Eurographics Symposium on Parallel Graphics and Visualization, The Eurographics Association, 2021.
DOI: 10.2312/pgv.20211040


In situ computation of Lagrangian flow maps to enable post hoc time-varying vector field analysis has recently become an active area of research. However, the current literature is largely limited to theoretical settings and lacks a solution to address scalability of the technique in distributed memory. To improve scalability, we propose and evaluate the benefits and limitations of a simple, yet novel, performance optimization. Our proposed optimization is a communication-free model resulting in local Lagrangian flow maps, requiring no message passing or synchronization between processes, intrinsically improving scalability, and thereby reducing overall execution time and alleviating the encumbrance placed on simulation codes from communication overheads. To evaluate our approach, we computed Lagrangian flow maps for four time-varying simulation vector fields and investigated how execution time and reconstruction accuracy are impacted by the number of GPUs per compute node, the total number of compute nodes, particles per rank, and storage intervals. Our study consisted of experiments computing Lagrangian flow maps with up to 67M particle trajectories over 500 cycles and used as many as 2048 GPUs across 512 compute nodes. In all, our study contributes an evaluation of a communication-free model as well as a scalability study of computing distributed Lagrangian flow maps at scale using in situ infrastructure on a modern supercomputer.

S. Sane, C. R. Johnson, H. Childs. “Investigating In Situ Reduction via Lagrangian Representations for Cosmology and Seismology Applications,” In Computational Science -- ICCS 2021, Springer International Publishing, pp. 436--450. 2021.
DOI: 10.1007/978-3-030-77961-0_36


Although many types of computational simulations produce time-varying vector fields, subsequent analysis is often limited to single time slices due to excessive costs. Fortunately, a new approach using a Lagrangian representation can enable time-varying vector field analysis while mitigating these costs. With this approach, a Lagrangian representation is calculated while the simulation code is running, and the result is explored after the simulation. Importantly, the effectiveness of this approach varies based on the nature of the vector field, requiring in-depth investigation for each application area. With this study, we evaluate the effectiveness for previously unexplored cosmology and seismology applications. We do this by considering encumbrance (on the simulation) and accuracy (of the reconstructed result). To inform encumbrance, we integrated in situ infrastructure with two simulation codes, and evaluated on representative HPC environments, performing Lagrangian in situ reduction using GPUs as well as CPUs. To inform accuracy, our study conducted a statistical analysis across a range of spatiotemporal configurations as well as a qualitative evaluation. In all, we demonstrate effectiveness for both cosmology and seismology—time-varying vector fields from these domains can be reduced to less than 1% of the total data via Lagrangian representations, while maintaining accurate reconstruction and requiring under 10% of total execution time in over 80% of our experiments.

A. Singh, M. Bauer, S. Joshi. “Physics Informed Convex Artificial Neural Networks (PICANNs) for Optimal Transport based Density Estimation,” Subtitled “arXiv,” 2021.


Optimal Mass Transport (OMT) is a well studied problem with a variety of applications in a diverse set of fields ranging from Physics to Computer Vision and in particular Statistics and Data Science. Since the original formulation of Monge in 1781 significant theoretical progress been made on the existence, uniqueness and properties of the optimal transport maps. The actual numerical computation of the transport maps, particularly in high dimensions, remains a challenging problem. By Brenier's theorem, the continuous OMT problem can be reduced to that of solving a non-linear PDE of Monge-Ampere type whose solution is a convex function. In this paper, building on recent developments of input convex neural networks and physics informed neural networks for solving PDE's, we propose a Deep Learning approach to solve the continuous OMT problem.

To demonstrate the versatility of our framework we focus on the ubiquitous density estimation and generative modeling tasks in statistics and machine learning. Finally as an example we show how our framework can be incorporated with an autoencoder to estimate an effective probabilistic generative model.

P. Subedi, P.E .Davis, M. Parashar. “RISE: Reducing I/O Contention in Staging-based Extreme-Scale In-situ Workflows,” In 2021 IEEE International Conference on Cluster Computing (CLUSTER), pp. 146--156. 2021.


While in-situ workflow formulations have addressed some of the data-related challenges associated with extreme-scale scientific workflows, these workflows involve complex interactions and different modes of data exchange. In the context of increasing system complexity, such workflows present significant resource management challenges, requiring complex cost-performance tradeoffs. This paper presents RISE, an intelligent staging-based data management middleware, which builds on the DataSpaces framework and performs intelligent scheduling of data management operations to reduce I/O contention. In RISE, data are always written immediately to local buffers to reduce the effect of the transfer impact upon application performance. RISE identifies applications’ data access patterns and moves data towards data consumers only when the network is expected to be idle, reducing the impact of asynchronous …

E. Suchyta, S. Klasky, N. Podhorszki, M. Wolf, A. Adesoji, C.S. Chang, J. Choi, P. E. Davis, J. Dominski, S. Ethier, I. Foster, K. Germaschewski, B. Geveci, C. Harris, K. A. Huck, Q. Liu, J. Logan, K. Mehta, G. Merlo, S. V. Moore, T. Munson, M. Parashar, D. Pugmire, M. S. Shephard, C. W. Smith, P. Subedi, L. Wan, R. Wang, S. Zhang. “The Exascale Framework for High Fidelity coupled Simulations (EFFIS): Enabling whole device modeling in fusion science,” In The International Journal of High Performance Computing Applications, SAGE Publications, pp. 10943420211019119. 2021.


We present the Exascale Framework for High Fidelity coupled Simulations (EFFIS), a workflow and code coupling framework developed as part of the Whole Device Modeling Application (WDMApp) in the Exascale Computing Project.EFFIS consists of a library, command line utilities, and a collection of run-time daemons. Together, these software products enable users to easily compose and execute workflows that include: strong or weak coupling, in situ (or offline)analysis/visualization/monitoring, command-and-control actions, remote dashboard integration, and more. We describe WDMApp physics coupling cases and computer science requirements that motivate the design of the EFFIS framework. Furthermore, we explain the essential enabling technology that EFFIS leverages: ADIOS for performant data movement, PerfStubs/TAU for performance monitoring, and an advanced COUPLER for transforming coupling data from its native format to the representation needed by another application. Finally, we demonstrate EFFIS using coupled multi-simulation WDMApp workflows and exemplify how the framework supports the project’s needs. We show that EFFIS and its associated services for data movement, visualization, and performance collection does not introduce appreciable overhead to the WDMApp workflow and that the resource-dominant application’s idle time while waiting for data is minimal.

T. Sun, D. Li, B. Wang. “Decentralized Federated Averaging,” Subtitled “arXiv preprint arXiv:2104.11375,” 2021.


Federated averaging (FedAvg) is a communication efficient algorithm for the distributed training with an enormous number of clients. In FedAvg, clients keep their data locally for privacy protection; a central parameter server is used to communicate between clients. This central server distributes the parameters to each client and collects the updated parameters from clients. FedAvg is mostly studied in centralized fashions, which requires massive communication between server and clients in each communication. Moreover, attacking the central server can break the whole system's privacy. In this paper, we study the decentralized FedAvg with momentum (DFedAvgM), which is implemented on clients that are connected by an undirected graph. In DFedAvgM, all clients perform stochastic gradient descent with momentum and communicate with their neighbors only. To further reduce the communication cost, we also consider the quantized DFedAvgM. We prove convergence of the (quantized) DFedAvgM under trivial assumptions; the convergence rate can be improved when the loss function satisfies the P\L property. Finally, we numerically verify the efficacy of DFedAvgM.

T. Sun, D. Li, B. Wang. “Stability and Generalization of the Decentralized Stochastic Gradient Descent,” Subtitled “arXiv preprint arXiv:2102.01302,” 2021.


The stability and generalization of stochastic gradient-based methods provide valuable insights into understanding the algorithmic performance of machine learning models. As the main workhorse for deep learning, stochastic gradient descent has received a considerable amount of studies. Nevertheless, the community paid little attention to its decentralized variants. In this paper, we provide a novel formulation of the decentralized stochastic gradient descent. Leveraging this formulation together with (non) convex optimization theory, we establish the first stability and generalization guarantees for the decentralized stochastic gradient descent. Our theoretical results are built on top of a few common and mild assumptions and reveal that the decentralization deteriorates the stability of SGD for the first time. We verify our theoretical findings by using a variety of decentralized settings and benchmark machine learning models.

W. Tao, R. Bhalodia, R. Whitaker. “A Gaussian Process Model for Unsupervised Analysis of High Dimensional Shape Data,” In Machine Learning in Medical Imaging, Springer International Publishing, pp. 356--365. 2021.
DOI: 10.1007/978-3-030-87589-3_37


Applications of medical image analysis are often faced with the challenge of modelling high-dimensional data with relatively few samples. In many settings, normal or healthy samples are prevalent while pathological samples are rarer, highly diverse, and/or difficult to model. In such cases, a robust model of the normal population in the high-dimensional space can be useful for characterizing pathologies. In this context, there is utility in hybrid models, such as probabilistic PCA, which learns a low-dimensional model, commensurates with the available data, and combines it with a generic, isotropic noise model for the remaining dimensions. However, the isotropic noise model ignores the inherent correlations that are evident in so many high-dimensional data sets associated with images and shapes in medicine. This paper describes a method for estimating a Gaussian model for collections of images or shapes that exhibit underlying correlations, e.g., in the form of smoothness. The proposed method incorporates a Gaussian-process noise model within a generative formulation. For optimization, we derive a novel expectation maximization (EM) algorithm. We demonstrate the efficacy of the method on synthetic examples and on anatomical shape data.

J. D. Tate, W. W. Good, N. Zemzemi, M. Boonstra, P. van Dam, D. H. Brooks, A. Narayan, R. S. MacLeod. “Uncertainty Quantification of the Effects of Segmentation Variability in ECGI,” In Functional Imaging and Modeling of the Heart, Springer International Publishing, pp. 515--522. 2021.
DOI: 10.1007/978-3-030-78710-3_49


Despite advances in many of the techniques used in Electrocardiographic Imaging (ECGI), uncertainty remains insufficiently quantified for many aspects of the pipeline. The effect of geometric uncertainty, particularly due to segmentation variability, may be the least explored to date. We use statistical shape modeling and uncertainty quantification (UQ) to compute the effect of segmentation variability on ECGI solutions. The shape model was made with Shapeworks from nine segmentations of the same patient and incorporated into an ECGI pipeline. We computed uncertainty of the pericardial potentials and local activation times (LATs) using polynomial chaos expansion (PCE) implemented in UncertainSCI. Uncertainty in pericardial potentials from segmentation variation mirrored areas of high variability in the shape model, near the base of the heart and the right ventricular outflow tract, and that ECGI was less sensitive to uncertainty in the posterior region of the heart. Subsequently LAT calculations could vary dramatically due to segmentation variability, with a standard deviation as high as 126ms, yet mainly in regions with low conduction velocity. Our shape modeling and UQ pipeline presented possible uncertainty in ECGI due to segmentation variability and can be used by researchers to reduce said uncertainty or mitigate its effects. The demonstrated use of statistical shape modeling and UQ can also be extended to other types of modeling pipelines.

M. Thorpe, B. Wang. “Robust Certification for Laplace Learning on Geometric Graphs,” Subtitled “arXiv preprint arXiv:2104.10837,” 2021.


Graph Laplacian (GL)-based semi-supervised learning is one of the most used approaches for classifying nodes in a graph. Understanding and certifying the adversarial robustness of machine learning (ML) algorithms has attracted large amounts of attention from different research communities due to its crucial importance in many security-critical applied domains. There is great interest in the theoretical certification of adversarial robustness for popular ML algorithms. In this paper, we provide the first adversarial robust certification for the GL classifier. More precisely we quantitatively bound the difference in the classification accuracy of the GL classifier before and after an adversarial attack. Numerically, we validate our theoretical certification results and show that leveraging existing adversarial defenses for the -nearest neighbor classifier can remarkably improve the robustness of the GL classifier.

J. P. Torres, Z. Lin, M. Watkins, P. F. Salcedo, R. P. Baskin, S. Elhabian, H. Safavi-Hemami, D. Taylor, J. Tun, G. P. Concepcion, N. Saguil, A. A. Yanagihara, Y. Fang, J. R. McArthur, H. Tae, R. K. Finol-Urdaneta, B. D. Özpolat, B. M. Olivera, E. W. Schmidt. “Small-molecule mimicry hunting strategy in the imperial cone snail, Conus imperialis,” In Science Advances, Vol. 7, No. 11, American Association for the Advancement of Science, 2021.


Venomous animals hunt using bioactive peptides, but relatively little is known about venom small molecules and the resulting complex hunting behaviors. Here, we explored the specialized metabolites from the venom of the worm-hunting cone snail, Conus imperialis. Using the model polychaete worm Platynereis dumerilii, we demonstrate that C. imperialis venom contains small molecules that mimic natural polychaete mating pheromones, evoking the mating phenotype in worms. The specialized metabolites from different cone snails are species-specific and structurally diverse, suggesting that the cones may adopt many different prey-hunting strategies enabled by small molecules. Predators sometimes attract prey using the prey’s own pheromones, in a strategy known as aggressive mimicry. Instead, C. imperialis uses metabolically stable mimics of those pheromones, indicating that, in biological mimicry, even the molecules themselves may be disguised, providing a twist on fake news in chemical ecology.