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By conducting the differential analysis for de novo patients and for the entire cohort of PD patients, with the described additional filtering and covariate adjustments, we identified the set of shared significant differential metabolites with the same direction of the change in these two analyses as the set of high-confidence PD-associated metabolites, whose alterations are both independent of treatment effects (as confirmed by the de novo differential analysis) and robust across a large sample size (as confirmed by the analysis of the entire PD dataset)

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