Project 196 (PPMI 1)

A study document can be found at https://ida.loni.usc.edu/download/files/study/4bb082de-fa77-40ce-9dc5-494ec7fc0a1f/file/ppmi/PPMI_Project_196_Methods_Explore_20221212.pdf.

Briefly, project 196 is a longitudinal Olink proteomics study of de-novo PD and non-genetic prodromal participants age 60 or older with RBD or hyposmia and DAT deficit, with repeat sampling over 4 years. Data from study 196 were downloaded, totaling 924 CSF samples and 1160 plasma samples. The data are provided in Olink NPX units, a normalized arbitrary unit derived from sequence counts. The Olink NPX calculation and QC process are described in a separate section for clarity. Project 196 documents describe the data generation occurred in two separate experimental batches more than one year apart, so a batch effect analysis using principal component analysis (PCA) was performed. A batch effect corresponding to the experimental batch was observed via PCA. The study design utilized bridging samples to allow for correction of batch effects. We noted 89 bridging samples in both CSF and plasma datasets. We performed a batch correction based on PLATEID, using the removeBatchEffect function in the limma package for R 4.0.3. We confirmed via PCA that this removed the experimental batch effect. After batch correction, NPX values for replicate bridging samples were averaged to avoid duplicates in downstream analysis. The dataset was then further filtered to include only samples in which DDC was detected, since a fraction of samples were missing data from the Olink Cardiometabolic panel which contains DDC. After merging the filtered and QC’d data with participant level metadata, there were 765 CSF samples from 257 participants, consisting of 180 PD, 439 HC, and 146 prodromal samples. There were 859 plasma samples from 274 participants, consisting of 193 PD, 439 HC, and 227 prodromal samples. These data were used for all downstream CSF and plasma analysis in PPMI. For analysis of baseline samples, there were 243 CSF samples (69 de novo PD, 130 HC, 44 prodromal) and 262 plasma samples (74 de novo PD, 130 HC, 58 prodromal).