Methods and apparatus are provided for the analysis of images of cells and extraction biologically-significant shape-related features from the cell images. The extracted features may be correlated with particular conditions induced by biologically-active agents with which cells have been treated, thereby enabling the automated analysis of cells based on cell shape parameters. In particular, the invention provides methods for segmentation of cells in an image using a combination of a reference component image data and cell shape-indicative marker image data in a watershed technique. Further, the invention provides a skeletonization and skeleton analysis technique for extracting biologically-relevant features from cell shapes.