Iterative pseudo balancing for stem cell microscopy image classification.

Many critical issues arise when training deep neural networks using limited biological datasets. These include overfitting, exploding/vanishing gradients and other inefficiencies which are exacerbated by class imbalances and can affect the overall accuracy of a model. There is a need to develop semi-supervised models that can reduce the need for large, balanced, manually annotated datasets so that researchers can easily employ neural networks for experimental analysis. In this work, Iterative Pseudo Balancing (IPB) is introduced to classify stem cell microscopy images while performing on the fly dataset balancing using a student-teacher meta-pseudo-label framework. In addition, multi-scale patches of multi-label images are incorporated into the network training to provide previously inaccessible image features with both local and global information for effective and efficient learning. The combination of these inputs is shown to increase the classification accuracy of the proposed deep neural network by 3[Formula: see text] over baseline, which is determined to be statistically significant. This work represents a novel use of pseudo-labeling for data limited settings, which are common in biological image datasets, and highlights the importance of the exhaustive use of available image features for improving performance of semi-supervised networks. The proposed methods can be used to reduce the need for expensive manual dataset annotation and in turn accelerate the pace of scientific research involving non-invasive cellular imaging.

Triplet-Net Classification of Contiguous Stem Cell Microscopy Images.

Cellular microscopy imaging is a common form of data acquisition for biological experimentation. Observation of gray-level morphological features allows for the inference of useful biological information such as cellular health and growth status. Cellular colonies can contain multiple cell types, making colony level classification very difficult. Additionally, cell types growing in a hierarchical, downstream fashion, can often look visually similar, although biologically distinct. In this paper, it is determined empirically that traditional deep Convolutional Neural Networks (CNN) and classical object recognition techniques are not sufficient to distinguish between these subtle visual differences, resulting in misclassifications. Instead, Triplet-net CNN learning is employed in a hierarchical classification scheme to improve the ability of the model to discern distinct, fine-grain features of two commonly confused morphological image-patch classes, namely Dense and Spread colonies. The Triplet-net method improves classification accuracy over a four-class deep neural network by  âˆ¼  3 %, a value that was determined to be statistically significant, as well as existing state-of-the-art image patch classification approaches and standard template matching. These findings allow for the accurate classification of multi-class cell colonies with contiguous boundaries, and increased reliability and efficiency of automated, high-throughput experimental quantification using non-invasive microscopy.

Generative Adversarial Networks for Morphological-Temporal Classification of Stem Cell Images.

Frequently, neural network training involving biological images suffers from a lack of data, resulting in inefficient network learning. This issue stems from limitations in terms of time, resources, and difficulty in cellular experimentation and data collection. For example, when performing experimental analysis, it may be necessary for the researcher to use most of their data for testing, as opposed to model training. Therefore, the goal of this paper is to perform dataset augmentation using generative adversarial networks (GAN) to increase the classification accuracy of deep convolutional neural networks (CNN) trained on induced pluripotent stem cell microscopy images. The main challenges are: 1. modeling complex data using GAN and 2. training neural networks on augmented datasets that contain generated data. To address these challenges, a temporally constrained, hierarchical classification scheme that exploits domain knowledge is employed for model learning. First, image patches of cell colonies from gray-scale microscopy images are generated using GAN, and then these images are added to the real dataset and used to address class imbalances at multiple stages of training. Overall, a 2% increase in both true positive rate and F1-score is observed using this method as compared to a straightforward, imbalanced classification network, with some greater improvements on a classwise basis. This work demonstrates that synergistic model design involving domain knowledge is key for biological image analysis and improves model learning in high-throughput scenarios.