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1. Instance Segmentation of Neural Cells

   Yi, J. ; Wu, P. ; Jiang, M. ; Hoeppner, D. J. ; Metaxas, D. ( September 2018 , ECCV 2018 workshop)

   Instance segmentation of neural cells plays an important role in brain study. However, this task is challenging due to the special shapes and behaviors of neural cells. Existing methods are not precise enough to capture their tiny structures, e.g., filopodia and lamellipodia, which are critical to the understanding of cell interaction and behavior. To this end, we propose a novel deep multi-task learning model to jointly detect and segment neural cells instance-wise. Our method is built upon SSD, with ResNet101 as the backbone to achieve both high detection accuracy and fast speed. Furthermore, unlike existing works which tend to produce wavy and inaccurate boundaries, we embed a deconvolution module into SSD to better capture details. Experiments on a dataset of neural cell microscopic images show that our method is able to achieve better per- formance in terms of accuracy and efficiency, comparing favorably with current state-of-the-art methods. 

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2. PIXEL-WISE NEURAL CELL INSTANCE SEGMENTATION

   Yi, J. ; Wu, P. ; Hoeppner, D. J. ; Metaxas, D. ( April 2018 , 2018 IEEE 15th International Symposium on Biomedical Imaging (ISBI 2018))

   Accurate cell instance segmentation plays an important role in the study of neural cell interactions, which are critical for understanding the development of brain. These interactions are performed through the filopodia and lamellipodia of neural cells, which are extremely tiny structures and as a result render most existing instance segmentation methods powerless to precisely capture them. To solve this issue, in this paper we present a novel hierarchical neural network comprising object detection and segmentation modules. Compared to previous work, our model is able to efficiently share and make full use of the information at different levels between the two modules. Our method is simple yet powerful, and experimental results show that it captures the contours of neural cells, especially the filopodia and lamellipodia, with high accuracy, and outperforms recent state of the art by a large margin. 

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3. An intrinsically interpretable neural network architecture for sequence-to-function learning

   https://doi.org/10.1093/bioinformatics/btad271  

   Balcı, Ali Tuğrul ; Ebeid, Mark Maher ; Benos, Panayiotis V. ; Kostka, Dennis ; Chikina, Maria ( June 2023 , Bioinformatics)

   Sequence-based deep learning approaches have been shown to predict a multitude of functional genomic readouts, including regions of open chromatin and RNA expression of genes. However, a major limitation of current methods is that model interpretation relies on computationally demanding post hoc analyses, and even then, one can often not explain the internal mechanics of highly parameterized models. Here, we introduce a deep learning architecture called totally interpretable sequence-to-function model (tiSFM). tiSFM improves upon the performance of standard multilayer convolutional models while using fewer parameters. Additionally, while tiSFM is itself technically a multilayer neural network, internal model parameters are intrinsically interpretable in terms of relevant sequence motifs.

   We analyze published open chromatin measurements across hematopoietic lineage cell-types and demonstrate that tiSFM outperforms a state-of-the-art convolutional neural network model custom-tailored to this dataset. We also show that it correctly identifies context-specific activities of transcription factors with known roles in hematopoietic differentiation, including Pax5 and Ebf1 for B-cells, and Rorc for innate lymphoid cells. tiSFM’s model parameters have biologically meaningful interpretations, and we show the utility of our approach on a complex task of predicting the change in epigenetic state as a function of developmental transition.

   The source code, including scripts for the analysis of key findings, can be found at https://github.com/boooooogey/ATAConv, implemented in Python.

    

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4. CONTEXT-REFINED NEURAL CELL INSTANCE SEGMENTATION

   Yi, J. ; Wu, P. ; Huang, Q. ; Qu, H. ; Hoeppner, D. J. ; Metaxas, D. ( April 2019 , 2019 IEEE 16th International Symposium on Biomedical Imaging (ISBI 2019))

   Neural cell instance segmentation serves as a valuable tool for the study of neural cell behaviors. In general, the instance segmentation methods compute the region of interest (ROI) through a detection module, where the segmentation is sub- sequently performed. To precisely segment the neural cells, especially their tiny and slender structures, existing work em- ploys a u-net structure to preserve the low-level details and encode the high-level semantics. However, such method is insufficient for differentiating the adjacent cells when large parts of them are included in the same cropped ROI. To solve this problem, we propose a context-refined neural cell instance segmentation model that learns to suppress the back- ground information. In particular, we employ a light-weight context refinement module to recalibrate the deep features and focus the model exclusively on the target cell within each cropped ROI. The proposed model is efficient and accurate, and experimental results demonstrate its superiority com- pared to the state-of-the-arts. 

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5. A hierarchical convolutional neural network for mitosis detection in phase-contrast microscopy images

   https://doi.org/10.1007/978-3-319-46723-8_79  

   Mao, Yunxiang ; Yin, Zhaozheng ( October 2016 , MICCAI 2016: Medical Image Computing and Computer-Assisted Intervention – MICCAI 2016)

   We propose a Hierarchical Convolution Neural Network (HCNN) for mitosis event detection in time-lapse phase contrast microscopy. Our method contains two stages: first,we extract candidate spatial-temporal patch sequences in the input image sequences which potentially contain mitosis events. Then,we identify if each patch sequence contains mitosis event or not using a hieratical convolutional neural network. In the experiments,we validate the design of our proposed architecture and evaluate the mitosis event detection performance. Our method achieves 99.1% precision and 97.2% recall in very challenging image sequences of multipolar-shaped C3H10T1/2 mesenchymal stem cells and outperforms other state-of-the-art methods. Furthermore,the proposed method does not depend on hand-crafted feature design or cell tracking. It can be straightforwardly adapted to event detection of other different cell types. 

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