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Confidence regions for a persistence diagram of a single image with one or more loops

  • *Corresponding author: Susan Glenn

    *Corresponding author: Susan Glenn 

Supported by NSF under Grant Number DMS 2038556, DMS 2337243, DMS 2245906; LANL under project number 20240479CR-IST; NIH under Grant Number RO1 GM052932.

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  • Topological data analysis (TDA) uses persistent homology to quantify loops and higher-dimensional holes in data, making it particularly relevant for examining the characteristics of images of cells in the field of cell biology. In the context of a cell injury, as time progresses, a wound in the form of a ring emerges in the cell image and then gradually vanishes. Performing statistical inference on this ring-like pattern in a single image is challenging due to the absence of repeated samples. In this paper, we develop a novel framework leveraging TDA to estimate underlying structures within an individual image and quantify associated uncertainties through confidence regions. Our proposed method partitions the image into the background and the damaged cell regions. Then, pixels within the affected cell region are used to establish confidence regions in the space of persistence diagrams (topological summary statistics). The proposed method establishes an estimate of a persistence diagram for an image that mitigates the bias of a traditional persistence diagram computation. A simulation study is conducted to evaluate the coverage probabilities of the proposed confidence regions in comparison to an alternative approach that is proposed in this paper. We also illustrate our methodology by a real-world example provided by biological cell repair.

    Mathematics Subject Classification: Primary: 62R40; Secondary: 62P10.

    Citation:

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  • Figure 1.  (A) Grey scale image of a protein ring formed around a wound where there was no toxin (control) injected into the cell. (B) Grey scale image of a protein ring formed around a wound where a toxin (C3) was injected into the cell

    Figure 2.  (A) Partitions of an underlying simulated pattern into background $ \mu_0 $, loop $ \mu_1 $, and interior of the loop $ \mu_{1*} $. (B) Partitions of the data image (observed) into into background, the loop, and the interior of the loop. Each $ Z^k $ denotes pixel intensity value for partition $ k = \{0,1,1*\} $ and each $ F_k $ is a distribution from which the pixel was drawn. (C) The simplicial complex $ \mathcal{K}_{3778} $ built on $ (\mathcal{M}^{\sigma})^{[3778,\infty)} $ contains one connected component and five loops; 3778 is the birth time of the true loop (loop number 1). (D) The simplicial complex $ \mathcal{K}_{3000} $ built on $ (\mathcal{M}^{\sigma})^{[3000,\infty)} $ contains five connected components and six loops. (E) The simplicial complex $ \mathcal{K}_{2512} $ built on $ (\mathcal{M}^{\sigma})^{[2512,\infty)} $ contains two connected components and no loops, where 2512 is the death time of the large loop born at $ \mathcal{K}_{3778} $

    Figure 3.  (A) The persistence diagram of the underlying pattern in Figure 2A which has only one loop (red triangle) and one connected component (black dots). (B) The persistence diagram of the data in Figure 2B with loops (red triangles) and connected components (black dots)

    Figure 4.  Illustration of simplicial complexes (purple) built on the upper-level sets at the birth time and death time of an image with a loop, with $ \mu_1 = 4000 $ and $ \mu_{1*} = 3000 $. (A) The simplicial complex $ \mathcal{K}_{b_j} = \mathcal{K}_{3597} $ at the birth of the loop where the black dot is the pixel with intensity value equal to 3597, which is the upper-level set threshold associated with the birth of the loop. The white rectangles indicate the pixels of $ \mathcal{M}^{\sigma}_1 $. (B) The simplicial complex $ \mathcal{K}_{d_j} = \mathcal{K}_{2593} $ at the death of the loop where the black dot is the pixel with intensity value equal to 2593, which is the upper-level set threshold associated with the death of the loop. The white rectangles, which indicate the pixels of $ \mathcal{M}^{\sigma}_{1*} $, appear light purple due to the overlaying two-simplices in $ \mathcal{K}_{d_j} $

    Figure 5.  Boxplots illustrating estimated birth (A) and death (B) times of loops using parTDA (red) and tTDA (blue), based on 100 iid images within each factor Level of loop thickness or dimensions. The true death and birth times are indicated by the horizontal solid black lines. The tTDA estimates have a strong negative bias with higher variability, while the proposed parTDA estimates appear to be unbiased with lower variability

    Figure 6.  Confidence regions and coverage before (misclassified) and after (corrected) Algorithm 2 has been applied. The misclassified segmentation $ \hat e $ has six pixels incorrectly classified. (A) Confidence regions for 100 images at noise level $ \sigma = \{50,100,300 \} $ are shown using $ \hat e $ (misclassified) and $ \hat e_{\text{new}} $ (corrected). The green dots indicate the true death and birth time location. (B) The coverage of the 95% confidence regions for $ \sigma = \{10, 50,100,200,300 \} $ for misclassified (red) and corrected (blue) segmentations, using 100 iid images

    Figure 7.  death and birth estimates (A) and confidence regions (B) of 100 images across four noise levels, $ \sigma = \{50,150,250,350 \} $. (A) Point estimates for $ (\mu_{1*}, \mu_1) $ using tTDA (triangle) and parTDA (asterisk), estimates of $ (\tilde \mu_{1*}, \tilde \mu_1) $ using sTDA (plus), and the true death and birth time of the manifold (black circle). (B) The $ 95 $% confidence regions for $ (\mu_{1*}, \mu_1) $ using parTDA and $ (\tilde \mu_{1*}, \tilde \mu_1) $ using sTDA

    Figure 8.  (A) An example of simulated images with multiple loops. (B) The confidence regions for the first two most persistent loops (blue and red) where the green points are the death and birth times of the true loops

    Figure 9.  (A) The top row displays the images for the control cell $ \mathcal{M}^{\text{control}}_t $ and the bottom row is the images for the C3 cell $ \mathcal{M}^{\text{C3}}_t $. The columns represent different time points, $ t_1 $, $ t_{10} $, $ t_{20} $, and $ t_{30} $. (B) Image of $ \mathcal{M}^{\text{C3}}_{t_{15}} $ segmented by $ e^{\text{C3}}_{15} $ where the black lines are the edges

    Figure 10.  Estimated persistences of the C3 and Control cell images from $ t = \{t_8,\ldots,t_{28}\} $. (A) The parTDA death and birth times are shown on the persistence diagram along with confidence regions for both the C3 cell (right) and the Control cell (left). The black line is the diagonal line $ b = d $. (B) Persistence is plotted over time for the C3 cell (solid line with points) and the Control cell (dashed line with triangles) using parTDA (red), sTDA (purple), and tTDA (light blue)

    Algorithm 1 Localizing the death and birth times $ (d_j,b_j) $
    1: Input: $ df\; := \;(x, y, Z[x,y]) $ of image $ \mathcal{M}^{\sigma} $ where $ Z[x,y] $ is pixel intensity; partitions $ \mathcal{G}_k $ for $ k=\{0,1,1*\} $, death and birth times from $ \mathcal{P}(M^{\sigma})\; := \;\{(d_1, b_1), \ldots, (d_{\beta_1}, b_{\beta_1})\} $.
    2: Output: $ (d_j, b_j) $ matched to $ (\mathcal{G}_{1*}, \mathcal{G}_{1}) $
    3: Define: $ df_k =\{(x,y,Z[x,y]) \in \mathcal{G}_k\} $, $ k=\{0,1,1*\} $; out$ _d=\emptyset $; out$ _b=\emptyset $; out$ =\emptyset $
    4: for l in 1:$ \beta_1 $ do
    5:     Step 1: Find $ df_k $ where $ Z(x,y)=d_l $     ▷Identify pixel location of $ d_l $ in $ \mathcal{G} $
    6:     if $ k=1* $ then out$ _d\leftarrow $ out$ _d\cup l $              ▷ Only keep index $ l $ for $ d_l \in \mathcal{G}_{1*} $
    7:     end if
    8:     Step 2: Find $ df_k $ where $ Z(x,y)=b_l $    ▷Identify pixel location of $ b_l $ in $ \mathcal{G} $
    9:     if $ k=1 $ out$ _b\leftarrow $ out$ _b\cup l $                          ▷Only keep index $ l $ for $ b_l \in \mathcal{G}_{1} $
    10:   end if
    11:   Step 3: Calculate out$ \leftarrow $out$ _d \cap $ out$ _b $
    12:   if length($ out $)==2 $ (d_l,b_l)=(d_j,b_j) $    ▷ If $ b_l \in \mathcal{G}_{1} $ and $ d_l \in \mathcal{G}_{1*} $ loop is matched
    13:        Stop                                                 ▷Match found, stop algorithm
    14:   end if
    15: end for
    16: return out
     | Show Table
    DownLoad: CSV
    Algorithm 2 Remove Misclassified Pixels from Partition ($ \mathcal{G}_1 $, $ \mathcal{G}_{1*} $)
    Input: edge set $ \hat{e} $; image $ \mathcal{M}^{\sigma} $; partitions $ \mathcal{\hat G}_1 $ and $ \mathcal{\hat G}_{1*} $; $ c $=pixel side length
    Output: new edge set $ \hat{e}^{\text{new}} $
    Define: $ \mathcal{\hat M}^{\sigma}_i=\{Z^i(x,y)_l : (x,y)_l \in \mathcal{\hat G}_i \} $, $ L_i=| \mathcal{\hat M}^{\sigma}_i|, $ $ P(Z^i(x,y) \leq q^i_{1})=0.25 $, $ P(Z^i(x,y) \leq q^i_{3})=0.75 $ for $ i=\{1,1*\} $; outlier$ _i=\emptyset $; outlier.idx$ _i=\emptyset $; dist()=Euclidean distance; $ e_1=\emptyset $
    for i in $ \{1,1*\} $ do
        for l in $ 1:L_i $ do ▷ Check if $ Z^i(x,y)_l $ is an outlier and neighbors an edge in $ \mathcal{\hat G}_i $
            if $ \left( (Z^i(x,y)_l > q^i_{3}+1.5(q^i_{3}-q^i_{1})) \mid (Z^i(x,y)_l < q^i_{1}-1.5(q^i_{3}-q^i_{1}))\right) $ & $ \left(\exists (\tilde x, \tilde y) \in \hat e\; s.t.\; \text{dist}((x,y)_l,(\tilde x, \tilde y)) \leq \sqrt{2}c \right) $ then $ \text{ outlier}_i\leftarrow \text{outlier}_i \cup Z^i(x,y)_l $, outlier.idx$ _i \leftarrow \text{outlier.idx}_i \cup l $
            end if
        end for
    end for
    Calculate $ \hat \mu_1=\mathcal{\hat M}^{\sigma}_1 \setminus $outlier$ _1 $ and $ \hat \mu_{1*}=\mathcal{\hat M}^{\sigma}_{1*} \setminus $outlier$ _{1*} $   ▷Calculate means without outliers
    for i in $ \{1,1*\} $ do
        for l in outlier.px$ _i $ do
            if $ \vert Z^i(x,y)_l-\hat \mu_i \vert \geq \vert Z^i(x,y)_l-\hat \mu_{i^c} \vert $ then     ▷ $ i^c $ is the complement in $ \{1,1*\} $ for $ i $ $ e_1\leftarrow e_1 \cup (x,y)_l $ ▷ only add $ (x,y)_l $ to new edge set $ e_1 $ if $ Z^i(x,y)_l $ is closer to $ \hat \mu_{i^c} $
            end if
        end for
    end for
    $ \hat e^{\text{new}} = \hat e \cup e_1 $
    return $ \hat e^{\text{new}} $
     | Show Table
    DownLoad: CSV

    Table 1.  Simulations results of a noisy loop for sTDA (rows 1-4) and parTDA (rows 5-8). The average confidence region area and standard errors (SE) are displayed for each noise level, based on 100 iid images in each setting. The fourth column is the percent coverage of the 95% confidence regions, and corresponding SEs

    Method Noise Level Average confidence region area (SE) Average coverage percentage (SE)
    sTDA 50 1390574 (5553.5) 100 (0)
    150 1460183 (9529.5) 100 (0)
    250 1577603 (14139.8) 100 (0)
    350 1746974 (28184.4) 100 (0)
    parTDA 50 122.9 (0.683) 94.7 (0.2)
    150 1099.3 (7.732) 95.3 (0.2)
    250 3057.2 (18.359) 94.6 (0.2)
    350 5980.2(30.602) 94.9 (0.3)
     | Show Table
    DownLoad: CSV

    Table 2.  Time results (in minutes) for applying sTDA and parTDA to an image with one loop where the segmentation includes segmenting the image and checking if any pixels are misclassified in the edge set using Algorithm 2

    Method Estimates Confidence Regions Segmentation Total
    sTDA 0.02 4.04 N/A 4.06
    parTDA 0.03 0.039 0.07 0.14
     | Show Table
    DownLoad: CSV
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