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Figure 1.

Process flow diagram for the proposed approach.

A preprocessing step is used to remove the background and uniform the light intensity conditions, then the segmentation process takes place with a two-dimensional version of the Enhanced Interaction Model. The resulting binary image is then enhanced through a cascade of morphological operators. Different colonies are then processed through a Watershed transform which returns as output the segmentation for each colony in the image.

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Figure 2.

Segmentation process.

(a): original image, (b): background subtraction. (c): colony segmentation, (d, e): orientation matching. (f): output image. Segmentation, identification and other outputs are shown overimposed on the original image (for a description see Figure 3).

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Figure 2 Expand

Table 1.

Table of the parameters adopted for the analysis.

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Table 1 Expand

Figure 3.

Segmentation examples.

(a, b, c): original images. (d, e, f): segmented colonies and identified spotted cells. Colonies are segmented with different colors: in each one the central blue star point is the centroid while small green circles identify marked cells; the segment from the centroid to the marked cell defines the normalization path, whose value is shown next to the small circle.

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Figure 4.

Distribution for the statistical analysis on the Zscan4-marked ES colony image set.

Distribution related to the distances from the centroid compared to the null case distribution, with a statistical difference p-value of with significance level .

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Figure 5.

Diagrams for the statistical analysis on the Zscan4-marked cells mutual distances.

Distribution related to the mutual distances compared to the null case distribution, with a p-value of with significance level .

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Figure 5 Expand

Figure 6.

Fluorescence images.

Union processing of two channels for the fluorescence microscopy images (this is from the 40 nanog-marked colony image set). (a): DAPI channel (blue), (b): Nanog channel (green), (c): resulting image; it was preprocessed so the colors were similar to those in the Zscan4 set so that the algorithm could be applied immediately.

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Figure 7.

Diagrams for the statistical analysis on the EndoA-marked ES colony image set.

Distribution related to the distances from the centroid compared to the null case distribution, with a statistical difference p-value of with significance level .

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Figure 7 Expand

Figure 8.

Diagrams for the statistical analysis on the EndoA-marked cell mutual distances.

Distribution related to the mutual distances compared to the null case distribution, with a p-value of with significance level .

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Figure 8 Expand

Figure 9.

Diagrams for the statistical analysis on the Nanog-marked ES colony image set.

Distribution related to the distances from the centroid compared to the null case distribution, with a statistical difference p-value of with significance level .

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Figure 9 Expand

Figure 10.

Diagrams for the statistical analysis on the Pou5f1-marked ES colony image set.

Distribution related to the distances from the centroid compared to the null case distribution, with a statistical difference p-value of with significance level .

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Figure 10 Expand