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      Weighted average ensemble-based semantic segmentation in biological electron microscopy images

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          Abstract

          Semantic segmentation of electron microscopy images using deep learning methods is a valuable tool for the detailed analysis of organelles and cell structures. However, these methods require a large amount of labeled ground truth data that is often unavailable. To address this limitation, we present a weighted average ensemble model that can automatically segment biological structures in electron microscopy images when trained with only a small dataset. Thus, we exploit the fact that a combination of diverse base-learners is able to outperform one single segmentation model. Our experiments with seven different biological electron microscopy datasets demonstrate quantitative and qualitative improvements. We show that the Grad-CAM method can be used to interpret and verify the prediction of our model. Compared with a standard U-Net, the performance of our method is superior for all tested datasets. Furthermore, our model leverages a limited number of labeled training data to segment the electron microscopy images and therefore has a high potential for automated biological applications.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s00418-022-02148-3.

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          Most cited references35

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          A survey on Image Data Augmentation for Deep Learning

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            Convolutional Neural Networks for Medical Image Analysis: Full Training or Fine Tuning?

            Training a deep convolutional neural network (CNN) from scratch is difficult because it requires a large amount of labeled training data and a great deal of expertise to ensure proper convergence. A promising alternative is to fine-tune a CNN that has been pre-trained using, for instance, a large set of labeled natural images. However, the substantial differences between natural and medical images may advise against such knowledge transfer. In this paper, we seek to answer the following central question in the context of medical image analysis: Can the use of pre-trained deep CNNs with sufficient fine-tuning eliminate the need for training a deep CNN from scratch? To address this question, we considered four distinct medical imaging applications in three specialties (radiology, cardiology, and gastroenterology) involving classification, detection, and segmentation from three different imaging modalities, and investigated how the performance of deep CNNs trained from scratch compared with the pre-trained CNNs fine-tuned in a layer-wise manner. Our experiments consistently demonstrated that 1) the use of a pre-trained CNN with adequate fine-tuning outperformed or, in the worst case, performed as well as a CNN trained from scratch; 2) fine-tuned CNNs were more robust to the size of training sets than CNNs trained from scratch; 3) neither shallow tuning nor deep tuning was the optimal choice for a particular application; and 4) our layer-wise fine-tuning scheme could offer a practical way to reach the best performance for the application at hand based on the amount of available data.
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              Opportunities and obstacles for deep learning in biology and medicine

              Deep learning describes a class of machine learning algorithms that are capable of combining raw inputs into layers of intermediate features. These algorithms have recently shown impressive results across a variety of domains. Biology and medicine are data-rich disciplines, but the data are complex and often ill-understood. Hence, deep learning techniques may be particularly well suited to solve problems of these fields. We examine applications of deep learning to a variety of biomedical problems—patient classification, fundamental biological processes and treatment of patients—and discuss whether deep learning will be able to transform these tasks or if the biomedical sphere poses unique challenges. Following from an extensive literature review, we find that deep learning has yet to revolutionize biomedicine or definitively resolve any of the most pressing challenges in the field, but promising advances have been made on the prior state of the art. Even though improvements over previous baselines have been modest in general, the recent progress indicates that deep learning methods will provide valuable means for speeding up or aiding human investigation. Though progress has been made linking a specific neural network's prediction to input features, understanding how users should interpret these models to make testable hypotheses about the system under study remains an open challenge. Furthermore, the limited amount of labelled data for training presents problems in some domains, as do legal and privacy constraints on work with sensitive health records. Nonetheless, we foresee deep learning enabling changes at both bench and bedside with the potential to transform several areas of biology and medicine.
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                Author and article information

                Contributors
                kavitha.shaga-devan@uni-ulm.de
                Journal
                Histochem Cell Biol
                Histochem Cell Biol
                Histochemistry and Cell Biology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0948-6143
                1432-119X
                20 August 2022
                20 August 2022
                2022
                : 158
                : 5
                : 447-462
                Affiliations
                [1 ]GRID grid.6582.9, ISNI 0000 0004 1936 9748, Central Facility of Electron Microscopy, , Ulm University, ; Albert Einstein-Allee 11, 89081 Ulm, Germany
                [2 ]GRID grid.6582.9, ISNI 0000 0004 1936 9748, Medical Systems Biology, , Ulm University, ; Albert Einstein-Alee 11, 89081 Ulm, Germany
                [3 ]GRID grid.410712.1, ISNI 0000 0004 0473 882X, Institute of Virology, , Ulm University Medical Center, ; Albert Einstein-Allee 11, 89081 Ulm, Germany
                Author information
                http://orcid.org/0000-0003-0745-9167
                Article
                2148
                10.1007/s00418-022-02148-3
                9630254
                35988009
                e66e9651-89ad-4d74-9656-178ba24aa31d
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 8 August 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100008316, Baden-Württemberg Stiftung;
                Award ID: ABEM
                Funded by: Universität Ulm (1055)
                Categories
                Original Paper
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2022

                Cell biology
                artificial intelligence,deep learning,automated image analysis,electron microscopy,semantic segmentation,ensemble-based machine learning

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