3D Shape Modeling for Cell Nuclear Morphological Analysis and Classification

Alexandr A. Kalinin, Ari Allyn-Feuer, Alex Ade, Gordon-Victor Fon, Walter Meixner, David Dilworth, Syed S. Husain, Jeffrey R. de Wett, Gerald A. Higgins, Gen Zheng, Amy Creekmore, John W. Wiley (+6 others)
<span title="2018-09-12">2018</span> <i title="Springer Nature America, Inc"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/tnqhc2x2aneavcd3gx5h7mswhm" style="color: black;">Scientific Reports</a> </i> &nbsp;
Quantitative analysis of morphological changes in a cell nucleus is important for the understanding of nuclear architecture and its relationship with pathological conditions such as cancer. However, dimensionality of imaging data, together with a great variability of nuclear shapes, presents challenges for 3D morphological analysis. Thus, there is a compelling need for robust 3D nuclear morphometric techniques to carry out population-wide analysis. We propose a new approach that combines
more &raquo; ... g, analysis, and interpretation of morphometric characteristics of cell nuclei and nucleoli in 3D. We used robust surface reconstruction that allows accurate approximation of 3D object boundary. Then, we computed geometric morphological measures characterizing the form of cell nuclei and nucleoli. Using these features, we compared over 450 nuclei with about 1,000 nucleoli of epithelial and mesenchymal prostate cancer cells, as well as 1,000 nuclei with over 2,000 nucleoli from serum-starved and proliferating fibroblast cells. Classification of sets of 9 and 15 cells achieved accuracy of 95.4% and 98%, respectively, for prostate cancer cells, and 95% and 98% for fibroblast cells. To our knowledge, this is the first attempt to combine these methods for 3D nuclear shape modeling and morphometry into a highly parallel pipeline workflow for morphometric analysis of thousands of nuclei and nucleoli in 3D. Motivation. Cell nuclear morphology is regulated by complex underlying biological mechanisms related to cell differentiation, development, proliferation, and disease 1-3 . Changes in the nuclear form are associated with reorganization of chromatin architecture related to altered functional properties such as gene regulation and expression 1,3 . Moreover, many studies in mechanobiology show that geometric constraints and mechanical forces applied to a cell deform it and, conversely, affect nuclear and chromatin dynamics, as well as gene and pathway activation 4,5 . Thus, nuclear morphological quantification becomes of major relevance as studies of the reorganization of the chromatin and DNA architecture in the spatial and temporal framework, known as the 4D nucleome, emerge 6,7 . Cellular structures of interest in the context of the 4D nucleome include not only the nucleus itself, but also the nucleolus and nucleolar-associating domains, chromosome territories, topologically associating domains, lamina-associating domains, and loop domains in transcription factories 6, 8 . Furthermore, understanding these processes through quantitative analysis of morphological changes also has many medical implications, for example, in detection, understanding, and treatment of pathological conditions such as cancer 7-10 . While efforts have been made to develop cell and nuclear shape characteristics in 2D or pseudo-3D 11, 12 , several studies have demonstrated that 3D morphometric measures provide better results for nuclear shape description and discrimination 13-15 . However, 3D shape descriptors that permit robust morphological analysis and facilitate human interpretation are still under active investigation 16 . Additionally, the dimensionality and volume of
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1038/s41598-018-31924-2">doi:10.1038/s41598-018-31924-2</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/30209281">pmid:30209281</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC6135819/">pmcid:PMC6135819</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/kqrmkyfhdvffzcskzkjwenve5q">fatcat:kqrmkyfhdvffzcskzkjwenve5q</a> </span>
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