Abstract
Interphase chromosomes are organized into discrete chromosome territories (CTs) that may occupy preferred sub-nuclear positions. While chromosome size and gene density appear to influence positioning, the biophysical mechanisms behind CT localization, especially the relationship between morphology and positioning, remain obscure. One reason for this has been the difficulty in imaging, segmenting, and analyzing structures with variable or imprecise boundaries. This prompted us to develop a novel approach, based on the two-dimensional (2D) wavelet-transform modulus maxima (WTMM) method, adapted to perform objective and rigorous CT segmentation from nuclear background. The wavelet transform acts as a mathematical microscope to characterize spatial image information over a continuous range of size scales. This multiresolution nature, combined with full objectivity of the formalism, makes it more accurate than intensity-based segmentation algorithms and more appropriate than manual intervention. Using the WTMM method in combination with numerical simulation models, we show that CTs have a highly nonspherical 3D morphology, that CT positioning is nonrandom, and favors heterologous CT groupings. We discuss potential relationships between morphology, positioning, chromosomal function, and instability.
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Supplemental Figure 1
Representation of an x–z view of the simulated nucleus used for both random models. Both poles of the nucleus have been flattened, by the slide and the cover slip respectively. This representation is obtained by taking the intersection between a sphere and two intersecting planes. The distance between the two planes is 3/4 the diameter of the sphere. (GIF 37.1 KB)
Supplemental Figure 2
Top row: First-order wavelet filtering of a pure (white) noise image shown in (A) at three increasing scales (B, C, and D), showing that no correlated structure appears. Bottom row: Same as above, but with the noisy image taken from main text Figure 5G with a ‘hidden’ cell nucleus with two chromosome territories, showing that the CT structure clearly appears at larger scales (H) and then can be followed across scales (G, F), thus illustrating how the WTMM method can detect such hidden objects through its multiresolution analysis (main text Figure 5). (GIF 506 KB)
Supplemental Figure 3
Example of a chromosome 15 image (A) for which the first-order wavelet algorithm failed to detect the lower left CT but the third-order wavelet algorithm succeeded (B). (GIF 30 KB)
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Khalil, A., Grant, J.L., Caddle, L.B. et al. Chromosome territories have a highly nonspherical morphology and nonrandom positioning. Chromosome Res 15, 899–916 (2007). https://doi.org/10.1007/s10577-007-1172-8
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DOI: https://doi.org/10.1007/s10577-007-1172-8