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Rapid diagnosis and analysis of human keloid scar tissues in an automated manner are essential for understanding pathogenesis and formulating treatment solutions. Our aim is to resolve the features of the extracellular matrix in human keloid scar tissues automatically for accurate diagnosis with the aid of machine learning. Multiphoton microscopy was utilized to acquire images of collagen and elastin fibers. Morphological features, histogram, and gray-level co-occurrence matrix-based texture features were obtained to produce a total of 28 features. The minimum redundancy maximum relevancy feature selection approach was implemented to rank these features and establish feature subsets, each of which was employed to build a machine learning model through the tree-based pipeline optimization tool (TPOT). The feature importance ranking was obtained, and 28 feature subsets were acquired by incremental feature selection. The subset with the top 23 features was identified as the most accurate. Then stochastic gradient descent classifier optimized by the TPOT was generated with an accuracy of 96.15% in classifying normal, scar, and adjacent tissues. The area under curve of the classification results (scar versus normal and adjacent, normal versus scar and adjacent, and adjacent versus normal and scar) was 1.0, 1.0, and 0.99, respectively. The proposed approach has great potential for future dermatological clinical diagnosis and analysis and holds promise for the development of computer-aided systems to assist dermatologists in diagnosis and treatment. [ABSTRACT FROM AUTHOR]