HAMIL: Hierarchical Aggregation-Based Multi-Instance Learning for Microscopy Image Classification

Multi-instance learning is common for computer vision tasks, especially in biomedical image processing. Traditional methods for multi-instance learning focus on designing feature aggregation methods and multi-instance classifiers, where the aggregation operation is performed either in feature extraction or learning phase. As deep neural networks (DNNs) achieve great success in image processing via automatic feature learning, certain feature aggregation mechanisms need to be incorporated into common DNN architecture for multi-instance learning. Moreover, flexibility and reliability are crucial considerations to deal with varying quality and number of instances. In this study, we propose a hierarchical aggregation network for multi-instance learning, called HAMIL. The hierarchical aggregation protocol enables feature fusion in a defined order, and the simple convolutional aggregation units lead to an efficient and flexible architecture. We assess the model performance on two microscopy image classification tasks, namely protein subcellular localization using immunofluorescence images and gene annotation using spatial gene expression images. The experimental results show that HAMIL outperforms the state-of-the-art feature aggregation methods and the existing models for addressing these two tasks. The visualization analyses also demonstrate the ability of HAMIL to focus on high-quality instances.

[1]  Ivan Laptev,et al.  Learning and Transferring Mid-level Image Representations Using Convolutional Neural Networks , 2014, 2014 IEEE Conference on Computer Vision and Pattern Recognition.

[2]  Qi Zhang,et al.  EM-DD: An Improved Multiple-Instance Learning Technique , 2001, NIPS.

[3]  Sethuraman Panchanathan,et al.  FlyExpress: visual mining of spatiotemporal patterns for genes and publications in Drosophila embryogenesis , 2011, Bioinform..

[4]  Dinggang Shen,et al.  Landmark‐based deep multi‐instance learning for brain disease diagnosis , 2018, Medical Image Anal..

[5]  Andrew Zisserman,et al.  Return of the Devil in the Details: Delving Deep into Convolutional Nets , 2014, BMVC.

[6]  Zhi-Hua Zhou,et al.  Neural Networks for Multi-Instance Learning , 2002 .

[7]  Xiu-Shen Wei,et al.  Scalable Algorithms for Multi-Instance Learning , 2017, IEEE Transactions on Neural Networks and Learning Systems.

[8]  Jian Sun,et al.  Deep Residual Learning for Image Recognition , 2015, 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[9]  G. Rubin,et al.  Global analysis of patterns of gene expression during Drosophila embryogenesis , 2007, Genome Biology.

[10]  Jitendra Jonnagaddala,et al.  Whole slide images based cancer survival prediction using attention guided deep multiple instance learning networks , 2020, Medical Image Anal..

[11]  Shuiwang Ji,et al.  Deep Convolutional Neural Networks for Multi-instance Multi-task Learning , 2015, 2015 IEEE International Conference on Data Mining.

[12]  Zhi-Hua Zhou,et al.  Multi-instance learning by treating instances as non-I.I.D. samples , 2008, ICML '09.

[13]  Geoffrey E. Hinton,et al.  Visualizing Data using t-SNE , 2008 .

[14]  M. Ashburner,et al.  Systematic determination of patterns of gene expression during Drosophila embryogenesis , 2002, Genome Biology.

[15]  Hong-Bin Shen,et al.  FlyIT: Drosophila Embryogenesis Image Annotation based on Image Tiling and Convolutional Neural Networks , 2019, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[16]  Chong-Wah Ngo,et al.  Evaluating bag-of-visual-words representations in scene classification , 2007, MIR '07.

[17]  Jun Wang,et al.  Solving the Multiple-Instance Problem: A Lazy Learning Approach , 2000, ICML.

[18]  Victor S. Lempitsky,et al.  Aggregating Deep Convolutional Features for Image Retrieval , 2015, ArXiv.

[19]  Bowen Zhou,et al.  Multiple instance learning with graph neural networks , 2019, ArXiv.

[20]  Thomas Hofmann,et al.  Support Vector Machines for Multiple-Instance Learning , 2002, NIPS.

[21]  Max Welling,et al.  Attention-based Deep Multiple Instance Learning , 2018, ICML.

[22]  Florent Perronnin,et al.  Large-scale image retrieval with compressed Fisher vectors , 2010, 2010 IEEE Computer Society Conference on Computer Vision and Pattern Recognition.

[23]  Cordelia Schmid,et al.  Aggregating local descriptors into a compact image representation , 2010, 2010 IEEE Computer Society Conference on Computer Vision and Pattern Recognition.

[24]  Stefan Carlsson,et al.  CNN Features Off-the-Shelf: An Astounding Baseline for Recognition , 2014, 2014 IEEE Conference on Computer Vision and Pattern Recognition Workshops.

[25]  Koen E. A. van de Sande,et al.  Selective Search for Object Recognition , 2013, International Journal of Computer Vision.

[26]  E. Lundberg,et al.  Towards a knowledge-based Human Protein Atlas , 2010, Nature Biotechnology.

[27]  James R. Foulds,et al.  A review of multi-instance learning assumptions , 2010, The Knowledge Engineering Review.

[28]  Dongqing Zhang,et al.  Neural Aggregation Network for Video Face Recognition , 2016, 2017 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[29]  Zhi-Hua Zhou,et al.  Improve Multi-Instance Neural Networks through Feature Selection , 2004, Neural Processing Letters.

[30]  Thomas Gärtner,et al.  Multi-Instance Kernels , 2002, ICML.

[31]  Yann Chevaleyre,et al.  Solving Multiple-Instance and Multiple-Part Learning Problems with Decision Trees and Rule Sets. Application to the Mutagenesis Problem , 2001, Canadian Conference on AI.

[32]  Jieping Ye,et al.  Drosophila Gene Expression Pattern Annotation through Multi-Instance Multi-Label Learning , 2009, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[33]  Brendan J. Frey,et al.  Classifying and segmenting microscopy images with deep multiple instance learning , 2015, Bioinform..

[34]  Subhransu Maji,et al.  Multi-view Convolutional Neural Networks for 3D Shape Recognition , 2015, 2015 IEEE International Conference on Computer Vision (ICCV).

[35]  Yee Whye Teh,et al.  Set Transformer , 2018, ICML.

[36]  Hong-Bin Shen,et al.  AnnoFly: annotating Drosophila embryonic images based on an attention-enhanced RNN model , 2019, Bioinform..

[37]  Zhi-Hua Zhou Multi-Instance Learning : A Survey , 2004 .

[38]  Hong-Bin Shen,et al.  ImPLoc: a multi-instance deep learning model for the prediction of protein subcellular localization based on immunohistochemistry images , 2019, Bioinform..

[39]  Wenyu Liu,et al.  Revisiting multiple instance neural networks , 2016, Pattern Recognit..

[40]  Ji Feng,et al.  Deep MIML Network , 2017, AAAI.

[41]  Jimmy Ba,et al.  Adam: A Method for Stochastic Optimization , 2014, ICLR.