Comparison of Artificial Intelligence based approaches to cell function prediction

Predicting Retinal Pigment Epithelium (RPE) cell functions in stem cell implants using non-invasive bright field microscopy imaging is a critical task for clinical deployment of stem cell therapies. Such cell function predictions can be carried out using Artificial Intelligence (AI) based models. In this paper we used Traditional Machine Learning (TML) and Deep Learning (DL) based AI models for cell function prediction tasks. TML models depend on feature engineering and DL models perform feature engineering automatically but have higher modeling complexity. This work aims at exploring the tradeoffs between three approaches using TML and DL based models for RPE cell function prediction from microscopy images and at understanding the accuracy relationship between pixel-, cell feature-, and implant label-level accuracies of models. Among the three compared approaches to cell function prediction, the direct approach to cell function prediction from images is slightly more accurate in comparison to indirect approaches using intermediate segmentation and/or feature engineering steps. We also evaluated accuracy variations with respect to model selections (five TML models and two DL models) and model configurations (with and without transfer learning). Finally, we quantified the relationships between segmentation accuracy and the number of samples used for training a model, segmentation accuracy and cell feature error, and cell feature error and accuracy of implant labels. We concluded that for the RPE cell data set, there is a monotonic relationship between the number of training samples and image segmentation accuracy, and between segmentation accuracy and cell feature error, but there is no such a relationship between segmentation accuracy and accuracy of RPE implant labels.

[1]  Xiujuan Lei,et al.  Random walk based method to identify essential proteins by integrating network topology and biological characteristics , 2019, Knowl. Based Syst..

[2]  ByoungChul Ko,et al.  Cell image classification based on ensemble features and random forest , 2011 .

[3]  Andrew Zisserman,et al.  Microscopy cell counting and detection with fully convolutional regression networks , 2018, Comput. methods Biomech. Biomed. Eng. Imaging Vis..

[4]  Reyer Zwiggelaar,et al.  Unsupervised Cell Nuclei Segmentation Based on Morphology and Adaptive Active Contour Modelling , 2013, ICIAR.

[5]  Kaiming He,et al.  Faster R-CNN: Towards Real-Time Object Detection with Region Proposal Networks , 2015, IEEE Transactions on Pattern Analysis and Machine Intelligence.

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

[7]  Ali Selman Aydin,et al.  CNN Based Yeast Cell Segmentation in Multi-modal Fluorescent Microscopy Data , 2017, 2017 IEEE Conference on Computer Vision and Pattern Recognition Workshops (CVPRW).

[8]  Allan Hanbury,et al.  Metrics for evaluating 3D medical image segmentation: analysis, selection, and tool , 2015, BMC Medical Imaging.

[9]  Bo Zhang,et al.  Neuron Segmentation Based on CNN with Semi-Supervised Regularization , 2016, 2016 IEEE Conference on Computer Vision and Pattern Recognition Workshops (CVPRW).

[10]  Karl Rohr,et al.  Comparison of segmentation methods for tissue microscopy images of glioblastoma cells , 2018, 2018 IEEE 15th International Symposium on Biomedical Imaging (ISBI 2018).

[11]  Q. Zou,et al.  Deep learning in omics: a survey and guideline , 2018, Briefings in functional genomics.

[12]  Mirabela Rusu,et al.  A deep learning-based algorithm for 2-D cell segmentation in microscopy images , 2018, BMC Bioinformatics.

[13]  Peter Bajcsy,et al.  Web Microanalysis of Big Image Data , 2018 .

[14]  David R Williams,et al.  Automated segmentation of retinal pigment epithelium cells in fluorescence adaptive optics images. , 2013, Journal of the Optical Society of America. A, Optics, image science, and vision.

[15]  Chandra Kambhamettu,et al.  DeepXScope: Segmenting Microscopy Images with a Deep Neural Network , 2017, 2017 IEEE Conference on Computer Vision and Pattern Recognition Workshops (CVPRW).

[16]  Ian H. Witten,et al.  The WEKA data mining software: an update , 2009, SKDD.

[17]  Michalis E. Zervakis,et al.  Detection and segmentation of drusen deposits on human retina: Potential in the diagnosis of age-related macular degeneration , 2003, Medical Image Anal..

[18]  Honglin Li,et al.  An improved sequence based prediction protocol for DNA-binding proteins using SVM and comprehensive feature analysis , 2012, BMC Bioinformatics.

[19]  Robert E. Schapire,et al.  Hierarchical multi-label prediction of gene function , 2006, Bioinform..

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

[21]  Wei Chen,et al.  Predicting protein structural classes for low-similarity sequences by evaluating different features , 2019, Knowl. Based Syst..

[22]  Andrew Zisserman,et al.  Very Deep Convolutional Networks for Large-Scale Image Recognition , 2014, ICLR.

[23]  Adnan Tufail,et al.  Phase 1 clinical study of an embryonic stem cell–derived retinal pigment epithelium patch in age-related macular degeneration , 2018, Nature Biotechnology.

[24]  A. Bird,et al.  Geographic atrophy: a histopathological assessment. , 2014, JAMA ophthalmology.

[25]  Adele P. Peskin,et al.  FogBank: a single cell segmentation across multiple cell lines and image modalities , 2014, BMC Bioinformatics.

[26]  Bo Wang,et al.  Machine Learning for Integrating Data in Biology and Medicine: Principles, Practice, and Opportunities , 2018, Inf. Fusion.

[27]  Olaf Strauss,et al.  The retinal pigment epithelium in visual function. , 2005, Physiological reviews.

[28]  Christoph Sommer,et al.  Machine learning in cell biology – teaching computers to recognize phenotypes , 2013, Journal of Cell Science.

[29]  M. E. Cuevas,et al.  Comparison of transepithelial resistance measurement techniques: Chopsticks vs. Endohm , 2017, Biological Procedures Online.

[30]  Mandy B. Esch,et al.  TEER Measurement Techniques for In Vitro Barrier Model Systems , 2015, Journal of laboratory automation.

[31]  Roberto Cipolla,et al.  SegNet: A Deep Convolutional Encoder-Decoder Architecture for Image Segmentation , 2015, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[32]  Li Fei-Fei,et al.  ImageNet: A large-scale hierarchical image database , 2009, CVPR.

[33]  Sean Ekins,et al.  Comparison of Deep Learning With Multiple Machine Learning Methods and Metrics Using Diverse Drug Discovery Data Sets. , 2017, Molecular pharmaceutics.

[34]  Ling Zhang,et al.  A deep learning based framework for accurate segmentation of cervical cytoplasm and nuclei , 2014, 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[35]  Kapil Bharti,et al.  Regenerating Retinal Pigment Epithelial Cells to Cure Blindness: A Road Towards Personalized Artificial Tissue , 2015, Current Stem Cell Reports.

[36]  Thomas Brox,et al.  U-Net: Convolutional Networks for Biomedical Image Segmentation , 2015, MICCAI.

[37]  Yoshua Bengio,et al.  How transferable are features in deep neural networks? , 2014, NIPS.

[38]  Nathan Hotaling,et al.  Clinical-grade stem cell–derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs , 2019, Science Translational Medicine.

[39]  Jelena Kovacevic,et al.  A multiresolution approach to automated classification of protein subcellular location images , 2007, BMC Bioinformatics.

[40]  Lovekesh Vig,et al.  Crowdsourcing for Chromosome Segmentation and Deep Classification , 2017, 2017 IEEE Conference on Computer Vision and Pattern Recognition Workshops (CVPRW).

[41]  J. Ambati,et al.  Mechanisms of Age-Related Macular Degeneration , 2012, Neuron.

[42]  Hai-Cheng Yi,et al.  A Deep Learning Framework for Robust and Accurate Prediction of ncRNA-Protein Interactions Using Evolutionary Information , 2018, Molecular therapy. Nucleic acids.

[43]  R.T. Smith,et al.  A hybrid segmentation approach for geographic atrophy in fundus auto-fluorescence images for diagnosis of age-related macular degeneration , 2007, 2007 29th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[44]  Nathan A Hotaling,et al.  Deep learning predicts function of live retinal pigment epithelium from quantitative microscopy. , 2019, The Journal of clinical investigation.