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• Multidimensional features were useful in separating pathological HFOs from physiological ones. • Machine learning classifier based on these features could well distinguish two types of HFOs. • The classification performance is robust among patients with different neuroimage finds and surgical outcomes. High-frequency oscillations (HFOs) are an efficient indicator to locate the epileptogenic zone (EZ). However, physiological HFOs produced in the normal brain region may interfere with EZ localization. The present study aimed to build a machine learning-based classifier to distinguish the properties of each HFO event based on features in different domains. HFOs were detected in focal epilepsy patients from two different hospitals who underwent stereoelectroencephalography and subsequent resection surgery. Subsequently, 37 features in four different domains (time, frequency and time-frequency, entropy-based and nonlinear) were extracted for each HFO. After extraction, a fast correlation-based filter (FCBF) algorithm was applied for feature selection. The machine learning classifier was trained on the feature matrix with and without FCBF and then tested on the data set from patients in another hospital. A dataset was compiled, consisting of 89,844 pathological HFOs and 23,613 physiological HFOs from 17 patients assigned to the training dataset. Additionally, 12,695 pathological HFOs and 5,599 physiological HFOs from 9 patients were assigned to the testing dataset. Four features (ripple band power, arithmetic mean, Petrosian fractal dimension and zero crossings) were obtained for classifier training after FCBF. The classifier showed an area under the curve (AUC) of 0.95/0.98 for FCBF/no FCBF features in the training dataset and AUC of 0.82/0.90 for FCBF/no FCBF features in the testing dataset. Our findings indicated that the classifier utilizing all features demonstrated superior performance compared to the one relying on FCBF-processed features. Our classifier could reliably differentiate pathological HFOs from physiological ones, which could promote the development of HFOs in EZ localization. [ABSTRACT FROM AUTHOR]