Context based mixture model for cell phase identification in automated fluorescence microscopy - PubMed (original) (raw)

Context based mixture model for cell phase identification in automated fluorescence microscopy

Meng Wang et al. BMC Bioinformatics. 2007.

Abstract

Background: Automated identification of cell cycle phases of individual live cells in a large population captured via automated fluorescence microscopy technique is important for cancer drug discovery and cell cycle studies. Time-lapse fluorescence microscopy images provide an important method to study the cell cycle process under different conditions of perturbation. Existing methods are limited in dealing with such time-lapse data sets while manual analysis is not feasible. This paper presents statistical data analysis and statistical pattern recognition to perform this task.

Results: The data is generated from Hela H2B GFP cells imaged during a 2-day period with images acquired 15 minutes apart using an automated time-lapse fluorescence microscopy. The patterns are described with four kinds of features, including twelve general features, Haralick texture features, Zernike moment features, and wavelet features. To generate a new set of features with more discriminate power, the commonly used feature reduction techniques are used, which include Principle Component Analysis (PCA), Linear Discriminant Analysis (LDA), Maximum Margin Criterion (MMC), Stepwise Discriminate Analysis based Feature Selection (SDAFS), and Genetic Algorithm based Feature Selection (GAFS). Then, we propose a Context Based Mixture Model (CBMM) for dealing with the time-series cell sequence information and compare it to other traditional classifiers: Support Vector Machine (SVM), Neural Network (NN), and K-Nearest Neighbor (KNN). Being a standard practice in machine learning, we systematically compare the performance of a number of common feature reduction techniques and classifiers to select an optimal combination of a feature reduction technique and a classifier. A cellular database containing 100 manually labelled subsequence is built for evaluating the performance of the classifiers. The generalization error is estimated using the cross validation technique. The experimental results show that CBMM outperforms all other classifies in identifying prophase and has the best overall performance.

Conclusion: The application of feature reduction techniques can improve the prediction accuracy significantly. CBMM can effectively utilize the contextual information and has the best overall performance when combined with any of the previously mentioned feature reduction techniques.

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Figures

Figure 1

Figure 1

A gray level image of a population of cells showing only nuclei channel. The image shows the nuclei after image enhancements.

Figure 4

Figure 4

Changes in the appearance of a nucleus during cell mitosis. From (a) to (h) consecutive image subframes form a sequence showing nuclei size and shape changes during cell mitosis.

Figure 5

Figure 5

An example of Continuous Gaussian Mixture Hidden Markov Model. M = 4, R = 2, the prior probability of phases are π i, i = 1,2,3,4 which are ignored in this picture.

Figure 2

Figure 2

Charts of average precision and sensitivity by CBMM and SVM. Charts (A), (C) show the average precision and sensitivity of different classifiers; while (B), (D) show the precision and sensitivity of the prophase cell identified by different classifiers.

Figure 3

Figure 3

Charts of average precision and sensitivity by KNN and BPNN. Charts (A), (C) show the average precision and sensitivity of different classifiers; while (B), (D) show the precision and sensitivity of the prophase cell identified by different classifiers.

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