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We analyzed clinical progression data (\u22655 years) of individuals with de novo PD using machine learning and deep learning, to characterize individuals\u2019 phenotypic progression trajectories for PD subtyping. We discovered three pace subtypes of PD exhibiting distinct progression patterns: the Inching Pace subtype (PD-I) with mild baseline severity and mild progression speed; the Moderate Pace subtype (PD-M) with mild baseline severity but advancing at a moderate progression rate; and the Rapid Pace subtype (PD-R) with the most rapid symptom progression rate. We found cerebrospinal fluid P-tau\/\u03b1-synuclein ratio and atrophy in certain brain regions as potential markers of these subtypes. Analyses of genetic and transcriptomic profiles with network-based approaches identified molecular modules associated with each subtype. For instance, the PD-R-specific module suggested <jats:italic>STAT3<\/jats:italic>, <jats:italic>FYN<\/jats:italic>, <jats:italic>BECN1<\/jats:italic>, <jats:italic>APOA1<\/jats:italic>, <jats:italic>NEDD4<\/jats:italic>, and <jats:italic>GATA2<\/jats:italic> as potential driver genes of PD-R. It also suggested neuroinflammation, oxidative stress, metabolism, PI3K\/AKT, and angiogenesis pathways as potential drivers for rapid PD progression (i.e., PD-R). Moreover, we identified repurposable drug candidates by targeting these subtype-specific molecular modules using network-based approach and cell line drug-gene signature data. We further estimated their treatment effects using two large-scale real-world patient databases; the real-world evidence we gained highlighted the potential of metformin in ameliorating PD progression. 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