A novel method based on atomic force microscopy (AFM) working in Ringing mode (RM) to distinguish between two similar human colon epithelial cancer cell lines that exhibit different degrees of neoplastic aggressiveness is reported on. The classification accuracy in identifying the cell line based on the images of a single cell can be as high as 94% (the area under the receiver operating characteristic [ROC] curve is 0.99). Comparing the accuracy using the RM and the regular imaging channels, it is seen that the RM channels are responsible for the high accuracy. The cells are also studied with a traditional AFM indentation method, which gives information about cell mechanics and the pericellular coat. Although a statistically significant difference between the two cell lines is also seen in the indentation method, it provides the accuracy of identifying the cell line at the single‐cell level less than 68% (the area under the ROC curve is 0.73). Thus, AFM cell imaging is substantially more accurate in identifying the cell phenotype than the traditional AFM indentation method. All the obtained cell data are collected on fixed cells and analyzed using machine learning methods. The biophysical reasons for the observed classification are discussed.
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Identification of Geometrical Features of Cell Surface Responsible for Cancer Aggressiveness: Machine Learning Analysis of Atomic Force Microscopy Images of Human Colorectal Epithelial Cells
It has been recently demonstrated that atomic force microscopy (AFM) allows for the rather precise identification of malignancy in bladder and cervical cells. Furthermore, an example of human colorectal epithelial cells imaged in AFM Ringing mode has demonstrated the ability to distinguish cells with varying cancer aggressiveness with the help of machine learning (ML). The previously used ML methods analyzed the entire cell image. The problem with such an approach is the lack of information about which features of the cell surface are associated with a high degree of aggressiveness of the cells. Here we suggest a machine-learning approach to overcome this problem. Our approach identifies specific geometrical regions on the cell surface that are critical for classifying cells as highly or lowly aggressive. Such localization gives a path to colocalize the newly identified features with possible clustering of specific molecules identified via standard bio-fluorescence imaging. The biological interpretation of the obtained information is discussed.
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- Award ID(s):
- 2224708
- PAR ID:
- 10432191
- Date Published:
- Journal Name:
- Biomedicines
- Volume:
- 11
- Issue:
- 1
- ISSN:
- 2227-9059
- Page Range / eLocation ID:
- 191
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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