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Ovarian cancer survival depends strongly on the time of diagnosis. Detection at stage 1 must be the goal of liquid biopsies for ovarian cancer detection. We report the development and validation of graphene-based optical nanobiosensors (G-NBSs) that quantify the activities of a panel of proteases, which were selected to provide a crowd response that is specific for ovarian cancer. These G-NBSs consist of few-layer explosion graphene featuring a hydrophilic coating, which is linked to fluorescently labeled highly selective consensus sequences for the proteases of interest, as well as a fluorescent dye. The panel of G-NBSs showed statistically significant differences in protease activities when comparing localized (early-stage) ovarian cancer with both metastatic (late-stage) and healthy control groups. A hierarchical framework integrated with active learning (AL) as a prediction and analysis tool for early-stage detection of ovarian cancer was implemented, which obtained an overall accuracy score of 94.5%, with both a sensitivity and specificity of 0.94.