Cell Nuclear Morphology Analysis Using 3D Shape Modeling, Machine Learning and Visual Analytics

Quantitative analysis of morphological changes in a cell nucleus is important for the understanding of nuclear architecture and its relationship with cell differentiation, development, proliferation, and disease. Changes in the nuclear form are associated with reorganization of chromatin architecture related to altered functional properties such as gene regulation and expression. Understanding these processes through quantitative analysis of morphological changes is important not only for investigating nuclear organization, but also has clinical implications, for example, in detection and treatment of pathological conditions such as cancer. While efforts have been made to characterize nuclear shapes in two or pseudo-three dimensions, several studies have demonstrated that three dimensional (3D) representations provide better nuclear shape description, in part due to the high variability of nuclear morphologies. 3D shape descriptors that permit robust morphological analysis and facilitate human interpretation are still under active investigation. A few methods have been proposed to classify nuclear morphologies in 3D, however, there is a lack of publicly available 3D data for the evaluation and comparison of such algorithms. There is a compelling need for robust 3D nuclear morphometric techniques to carry out population-wide analyses. In this work, we address a number of these existing limitations. First, we present a largest publicly available, to-date, 3D microscopy imaging dataset for cell nuclear morphology analysis and classification. We provide a detailed description of the image analysis protocol, from segmentation to baseline evaluation of a number of popular classification algorithms using 2D and 3D voxel-based morphometric measures. We proposed a specific cross-validation scheme that accounts for possible batch effects in data. Second, we propose a new technique that combines mathematical modeling, machine learning, and interpretation of morphometric characteristics of cell nuclei and nucleoli in 3D. Employing robust and smooth surface reconstruction methods to accurately approximate 3D object boundary enables the establishment of homologies between different biological shapes. Then, we compute geometric morphological measures characterizing the form of cell nuclei and nucleoli. We combine these methods into a highly parallel computational pipeline workflow for automated morphological analysis of thousands of nuclei and nucleoli in 3D. We also describe the use of visual analytics and deep learning techniques for the analysis of nuclear morphology data. Third, we evaluate proposed methods for 3D surface morphometric analysis of our data. We improved the performance of morphological classification between epithelial vs mesenchymal human prostate cancer cells compared to the previously reported results due to the more accurate shape representation and the use of combined nuclear and nucleolar morphometry. We confirmed previously reported relevant morphological characteristics, and also reported new features that can provide insight in the underlying biological mechanisms of pathology of prostate cancer. We also assessed nuclear morphology changes associated with chromatin remodeling in drug-induced cellular reprogramming. We computed temporal trajectories reflecting morphological differences in astroglial cell sub-populations administered with 2 different treatments vs controls. We described specific changes in nuclear morphology that are characteristic of chromatin re-organization under each treatment, which previously has been only tentatively hypothesized in literature. Our approach demonstrated high classification performance on each of 3 different cell lines and reported the most salient morphometric characteristics. We conclude with the discussion of the potential impact of method development in nuclear morphology analysis on clinical decision-making and fundamental investigation of 3D nuclear architecture. We consider some open problems and future trends in this field.PHDBioinformaticsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/147598/1/akalinin_1.pd

Deep Learning for Automatic Pneumonia Detection

Pneumonia is the leading cause of death among young children and one of the top mortality causes worldwide. The pneumonia detection is usually performed through examine of chest X-ray radiograph by highly-trained specialists. This process is tedious and often leads to a disagreement between radiologists. Computer-aided diagnosis systems showed the potential for improving diagnostic accuracy. In this work, we develop the computational approach for pneumonia regions detection based on single-shot detectors, squeeze-and-excitation deep convolution neural networks, augmentations and multi-task learning. The proposed approach was evaluated in the context of the Radiological Society of North America Pneumonia Detection Challenge, achieving one of the best results in the challenge.Comment: to appear in CVPR 2020 Workshops proceeding

FPGA Implementation of Convolutional Neural Networks with Fixed-Point Calculations

Neural network-based methods for image processing are becoming widely used in practical applications. Modern neural networks are computationally expensive and require specialized hardware, such as graphics processing units. Since such hardware is not always available in real life applications, there is a compelling need for the design of neural networks for mobile devices. Mobile neural networks typically have reduced number of parameters and require a relatively small number of arithmetic operations. However, they usually still are executed at the software level and use floating-point calculations. The use of mobile networks without further optimization may not provide sufficient performance when high processing speed is required, for example, in real-time video processing (30 frames per second). In this study, we suggest optimizations to speed up computations in order to efficiently use already trained neural networks on a mobile device. Specifically, we propose an approach for speeding up neural networks by moving computation from software to hardware and by using fixed-point calculations instead of floating-point. We propose a number of methods for neural network architecture design to improve the performance with fixed-point calculations. We also show an example of how existing datasets can be modified and adapted for the recognition task in hand. Finally, we present the design and the implementation of a floating-point gate array-based device to solve the practical problem of real-time handwritten digit classification from mobile camera video feed

Angiodysplasia Detection and Localization Using Deep Convolutional Neural Networks

Accurate detection and localization for angiodysplasia lesions is an important problem in early stage diagnostics of gastrointestinal bleeding and anemia. Gold-standard for angiodysplasia detection and localization is performed using wireless capsule endoscopy. This pill-like device is able to produce thousand of high enough resolution images during one passage through gastrointestinal tract. In this paper we present our winning solution for MICCAI 2017 Endoscopic Vision SubChallenge: Angiodysplasia Detection and Localization its further improvements over the state-of-the-art results using several novel deep neural network architectures. It address the binary segmentation problem, where every pixel in an image is labeled as an angiodysplasia lesions or background. Then, we analyze connected component of each predicted mask. Based on the analysis we developed a classifier that predict angiodysplasia lesions (binary variable) and a detector for their localization (center of a component). In this setting, our approach outperforms other methods in every task subcategory for angiodysplasia detection and localization thereby providing state-of-the-art results for these problems. The source code for our solution is made publicly available at https://github.com/ternaus/angiodysplasia-segmentatioComment: 12 pages, 6 figure

Determining specific power loss in joint area of laminated magnetic core

This paper discusses the method of analysis of specific power loss in the joint area of steel laminated core. The method is based on comparison of power loss data obtained from the tests of a circular shape magnetic core. Initially, the core build using uncut (solid) lamination sheets was tested to obtain the loss reference values. Then the laminations were cut onto four sections, and the core was tested again to obtain the loss increase associated with the implemented joint area. The test readings were processed to separate losses due to tangential and normal fluxes in the laminates. The processed data represented as relative p.u. values of increase in specific power loss have been extended to conduct an analysis of a rectangular magnetic core made using anisotropic, grain-oriented silicon electrical steel. The results demonstrated that the power loss produced by the normal magnetic flux dominates in the structure of total power loss in the rectangular core (approx. 85%). The proposed approach utilises the septation of losses produced by tangential and normal fluxes; it can be applied for the analysis of loss in the joint areas of magnetic cores of various power transformers

Analysis and experiential verification of power loss in joint area of laminated transformer core

This paper discusses the processes of power loss development in the joint area of the laminated transformer core due to eddy currents produced by the normal magnetic flux. Normal magnetic flux is directed in perpendicular to the plane of the laminations and the dominating factor in the power loss formation in the joint area. The analytical approach was verified by a set of tests where two experimental setups have been employed to investigate power loss in the laminations under various conditions. The tests provided data on the power loss produced by the normal flux in relation to the lamination width and lamination overlap length. It was shown that the power loss in the joint area significantly depends on the lamination width and is independent of lamination overlap

Hypothesis: Caco‐2 cell rotational 3D mechanogenomic turing patterns have clinical implications to colon crypts

Colon crypts are recognized as a mechanical and biochemical Turing patterning model. Colon epithelial Caco‐2 cell monolayer demonstrated 2D Turing patterns via force analysis of apical tight junction live cell imaging which illuminated actomyosin meshwork linking the actomyosin network of individual cells. Actomyosin forces act in a mechanobiological manner that alters cell/nucleus/tissue morphology. We observed the rotational motion of the nucleus in Caco‐2 cells that appears to be driven by actomyosin during the formation of a differentiated confluent epithelium. Single‐ to multi‐cell ring/torus‐shaped genomes were observed prior to complex fractal Turing patterns extending from a rotating torus centre in a spiral pattern consistent with a gene morphogen motif. These features may contribute to the well‐described differentiation from stem cells at the crypt base to the luminal colon epithelium along the crypt axis. This observation may be useful to study the role of mechanogenomic processes and the underlying molecular mechanisms as determinants of cellular and tissue architecture in space and time, which is the focal point of the 4D nucleome initiative. Mathematical and bioengineer modelling of gene circuits and cell shapes may provide a powerful algorithm that will contribute to future precision medicine relevant to a number of common medical disorders.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146665/1/jcmm13853.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146665/2/jcmm13853_am.pd

Reproducible image-based profiling with Pycytominer

Technological advances in high-throughput microscopy have facilitated the acquisition of cell images at a rapid pace, and data pipelines can now extract and process thousands of image-based features from microscopy images. These features represent valuable single-cell phenotypes that contain information about cell state and biological processes. The use of these features for biological discovery is known as image-based or morphological profiling. However, these raw features need processing before use and image-based profiling lacks scalable and reproducible open-source software. Inconsistent processing across studies makes it difficult to compare datasets and processing steps, further delaying the development of optimal pipelines, methods, and analyses. To address these issues, we present Pycytominer, an open-source software package with a vibrant community that establishes an image-based profiling standard. Pycytominer has a simple, user-friendly Application Programming Interface (API) that implements image-based profiling functions for processing high-dimensional morphological features extracted from microscopy images of cells. Establishing Pycytominer as a standard image-based profiling toolkit ensures consistent data processing pipelines with data provenance, therefore minimizing potential inconsistencies and enabling researchers to confidently derive accurate conclusions and discover novel insights from their data, thus driving progress in our field.Comment: 13 pages, 4 figure