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Deep Fish: Deep Learning-Based Classification of Zebrafish Deformation for High-Throughput Screening
Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0002-5129-530X
Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.ORCID iD: 0000-0002-4139-7003
2017 (English)In: Journal of Biomolecular Screening, ISSN 1087-0571, E-ISSN 1552-454X, Vol. 22, no 1, p. 102-107Article in journal (Refereed) Published
Abstract [en]

Zebrafish (Danio rerio) is an important vertebrate model organism in biomedical research, especially suitable for morphological screening due to its transparent body during early development. Deep learning has emerged as a dominant paradigm for data analysis and found a number of applications in computer vision and image analysis. Here we demonstrate the potential of a deep learning approach for accurate high-throughput classification of whole-body zebrafish deformations in multifish microwell plates. Deep learning uses the raw image data as an input, without the need of expert knowledge for feature design or optimization of the segmentation parameters. We trained the deep learning classifier on as few as 84 images (before data augmentation) and achieved a classification accuracy of 92.8% on an unseen test data set that is comparable to the previous state of the art (95%) based on user-specified segmentation and deformation metrics. Ablation studies by digitally removing whole fish or parts of the fish from the images revealed that the classifier learned discriminative features from the image foreground, and we observed that the deformations of the head region, rather than the visually apparent bent tail, were more important for good classification performance.

Place, publisher, year, edition, pages
2017. Vol. 22, no 1, p. 102-107
National Category
Signal Processing
Research subject
Computerized Image Processing
Identifiers
URN: urn:nbn:se:uu:diva-309535DOI: 10.1177/1087057116667894ISI: 000394206000012PubMedID: 27613194OAI: oai:DiVA.org:uu-309535DiVA, id: diva2:1051990
Funder
Swedish Research Council, 2012-4968eSSENCE - An eScience CollaborationAvailable from: 2016-12-05 Created: 2016-12-05 Last updated: 2017-11-17
In thesis
1. Deep Neural Networks and Image Analysis for Quantitative Microscopy
Open this publication in new window or tab >>Deep Neural Networks and Image Analysis for Quantitative Microscopy
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Understanding biology paves the way for discovering drugs targeting deadly diseases like cancer, and microscopy imaging is one of the most informative ways to study biology. However, analysis of large numbers of samples is often required to draw statistically verifiable conclusions. Automated approaches for analysis of microscopy image data makes it possible to handle large data sets, and at the same time reduce the risk of bias. Quantitative microscopy refers to computational methods for extracting measurements from microscopy images, enabling detection and comparison of subtle changes in morphology or behavior induced by varying experimental conditions. This thesis covers computational methods for segmentation and classification of biological samples imaged by microscopy.

Recent increase in computational power has enabled the development of deep neural networks (DNNs) that perform well in solving real world problems. This thesis compares classical image analysis algorithms for segmentation of bacteria cells and introduces a novel method that combines classical image analysis and DNNs for improved cell segmentation and detection of rare phenotypes. This thesis also demonstrates a novel DNN for segmentation of clusters of cells (spheroid), with varying sizes, shapes and textures imaged by phase contrast microscopy. DNNs typically require large amounts of training data. This problem is addressed by proposing an automated approach for creating ground truths by utilizing multiple imaging modalities and classical image analysis. The resulting DNNs are applied to segment unstained cells from bright field microscopy images. In DNNs, it is often difficult to understand what image features have the largest influence on the final classification results. This is addressed in an experiment where DNNs are applied to classify zebrafish embryos based on phenotypic changes induced by drug treatment. The response of the trained DNN is tested by ablation studies, which revealed that the networks do not necessarily learn the features most obvious at visual examination. Finally, DNNs are explored for classification of cervical and oral cell samples collected for cancer screening. Initial results show that the DNNs can respond to very subtle malignancy associated changes. All the presented methods are developed using open-source tools and validated on real microscopy images.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. p. 85
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1566
Keywords
Deep neural networks, convolutional neural networks, image analysis, quantitative microscopy, bright-field microscopy
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering Signal Processing
Research subject
Computerized Image Processing
Identifiers
urn:nbn:se:uu:diva-329834 (URN)978-91-513-0080-1 (ISBN)
Public defence
2017-11-10, 2446, ITC, Lägerhyddsvägen 2, Hus 2, Uppsala, 10:15 (English)
Opponent
Supervisors
Funder
Swedish Research Council, 2012-4968EU, European Research Council, 682810eSSENCE - An eScience Collaboration
Available from: 2017-10-17 Created: 2017-09-21 Last updated: 2018-03-08

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Ishaq, OmerSadanandan, Sajith KecherilWählby, Carolina

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