Virus Particle Detection by Convolutional Neural Network in Transmission Electron Microscopy Images

A new computational method for the detection of virus particles in transmission electron microscopy (TEM) images is presented. Our approach is to use a convolutional neural network that transforms a TEM image to a probabilistic map that indicates where virus particles exist in the image. Our proposed approach automatically and simultaneously learns both discriminative features and classifier for virus particle detection by machine learning, in contrast to existing methods that are based on handcrafted features that yield many false positives and require several postprocessing steps. The detection performance of the proposed method was assessed against a dataset of TEM images containing feline calicivirus particles and compared with several existing detection methods, and the state-of-the-art performance of the developed method for detecting virus was demonstrated. Since our method is based on supervised learning that requires both the input images and their corresponding annotations, it is basically used for detection of already-known viruses. However, the method is highly flexible, and the convolutional networks can adapt themselves to any virus particles by learning automatically from an annotated dataset.

[1]  P. Roingeard Viral detection by electron microscopy: past, present and future , 2008, Biology of the cell.

[2]  Bogdan J. Matuszewski,et al.  Hierarchical iterative Bayesian approach to automatic recognition of biological viruses in electron microscope images , 2001, Proceedings 2001 International Conference on Image Processing (Cat. No.01CH37205).

[3]  Maria da Conceição M. Sangreman Proenca,et al.  Automatic Virus Particle Selection—The Entropy Approach , 2013, IEEE Transactions on Image Processing.

[4]  Luca Maria Gambardella,et al.  Mitosis Detection in Breast Cancer Histology Images with Deep Neural Networks , 2013, MICCAI.

[5]  D. Sano,et al.  New tools for the study and direct surveillance of viral pathogens in water , 2008, Current Opinion in Biotechnology.

[6]  Nitish Srivastava,et al.  Dropout: a simple way to prevent neural networks from overfitting , 2014, J. Mach. Learn. Res..

[7]  Nitish Srivastava,et al.  Improving neural networks by preventing co-adaptation of feature detectors , 2012, ArXiv.

[8]  R. Glaeser,et al.  Review: automatic particle detection in electron microscopy. , 2001, Journal of structural biology.

[9]  Simon Haykin,et al.  GradientBased Learning Applied to Document Recognition , 2001 .

[10]  Doane Fw Virus morphology as an aid for rapid diagnosis. , 1980 .

[11]  Christopher Joseph Pal,et al.  Brain tumor segmentation with Deep Neural Networks , 2015, Medical Image Anal..

[12]  Xiaodong Gu,et al.  Towards dropout training for convolutional neural networks , 2015, Neural Networks.

[13]  Vinod Chandran,et al.  Identification of gastroenteric viruses by electron microscopy using higher order spectral features. , 2005, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[14]  Yann LeCun,et al.  Regularization of Neural Networks using DropConnect , 2013, ICML.

[15]  T S Baker,et al.  Identification of spherical virus particles in digitized images of entire electron micrographs. , 1997, Journal of structural biology.

[16]  G. Hall,et al.  A novel segmentation and classification method for identification of viruses in electron microscope images , 1997 .

[17]  Geoffrey E. Hinton,et al.  ImageNet classification with deep convolutional neural networks , 2012, Commun. ACM.

[18]  Yoshua Bengio,et al.  Gradient-based learning applied to document recognition , 1998, Proc. IEEE.

[19]  Emmanuelle Gouillart,et al.  scikit-image: image processing in Python , 2014, PeerJ.

[20]  J. Schramlová,et al.  The role of electron microscopy in the rapid diagnosis of viral infections — review , 2010, Folia Microbiologica.

[21]  Daisuke Sano,et al.  Microfluidic Quantitative PCR for Simultaneous Quantification of Multiple Viruses in Environmental Water Samples , 2014, Applied and Environmental Microbiology.

[22]  Luca Maria Gambardella,et al.  Deep Neural Networks Segment Neuronal Membranes in Electron Microscopy Images , 2012, NIPS.

[23]  Ida-Maria Sintorn,et al.  Virus Texture Analysis Using Local Binary Patterns and Radial Density Profiles , 2011, CIARP.

[24]  Molecular epidemiology of noroviruses detected in Nepalese children with acute diarrhea between 2005 and 2011: increase and predominance of minor genotype GII.13. , 2015, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[25]  Sergey Ioffe,et al.  Batch Normalization: Accelerating Deep Network Training by Reducing Internal Covariate Shift , 2015, ICML.

[26]  C. Söderberg-Nauclér,et al.  Identification and classification of human cytomegalovirus capsids in textured electron micrographs using deformed template matching , 2006, Virology Journal.

[27]  G. Borgefors,et al.  Segmentation of virus particle candidates in transmission electron microscopy images , 2012, Journal of microscopy.

[28]  Gunilla Borgefors,et al.  A refined circular template matching method for classification of human cytomegalovirus capsids in TEM images , 2004, Comput. Methods Programs Biomed..

[29]  Gaël Varoquaux,et al.  Scikit-learn: Machine Learning in Python , 2011, J. Mach. Learn. Res..