Campaign run · Parkinson's disease
parkinson-plasma-prodromal-panel-r2
…reported that an 8-protein plasma panel (Granulin/GRN, MASP2, HSPA5/BiP, PTGDS, ICAM1, complement C3, DKK3, SERPING1) distinguishes individuals with isolated REM-sleep behaviour disorder (iRBD) who will convert to Parkinson's disease within 7 years from those who will not, with area under the curve up to 1.0 in their internal cohort.
Status
- How far it got
- Stopped before planning
Stopped before writing any hypotheses: a dry-run test, a launch superseded by an immediate relaunch, a usage limit or a process failure.
- Why it stopped
This run stopped before the planning stage for an operational reason, not a scientific one. Runs in this group are dry-run tests, launches superseded by an immediate relaunch, runs that hit a usage limit, or one process failure. The released data do not say which of these applies to an individual run. No run in the campaign stopped before planning because data were unavailable.
- Recorded status
Stopped without a final status. The run stopped without recording a final status.
- Census class
Partial. Census class is a label from an earlier, process-level census of the campaign. It does not map one-to-one onto the stages above. How the classes compare.
Research question
The sentence under the run id is quoted from this brief.
Full research brief given to the run
Hällqvist J., Bartl M., Dakna M., ..., Mollenhauer B., Trenkwalder C. (Nat Commun 15:4759, 2024; DOI 10.1038/s41467-024-48961-3; PMC11189460; PRIDE PXD046355) reported that an 8-protein plasma panel (Granulin/GRN, MASP2, HSPA5/BiP, PTGDS, ICAM1, complement C3, DKK3, SERPING1) distinguishes individuals with isolated REM-sleep behaviour disorder (iRBD) who will convert to Parkinson's disease within 7 years from those who will not, with area under the curve up to 1.0 in their internal cohort.
The result is rare in PD biomarker literature: a small, interpretable panel measured by LC-MS/MS DIA in real plasma from a longitudinal prodromal cohort (DeNoPa + Oxford Discovery). It has not been formally replicated on the deposited MS spectra by an independent analysis pipeline, and the cross-platform generalisability (LC-MS/MS → other quantification) has not been established with deposited public data only.
This OmiCairn run formally tests:
H1 (primary — re-analysis of the deposited MS spectra replicates the 8-protein panel's predictive performance): Re-processing PXD046355 spectra with a from-scratch DIA-NN / Spectronaut-equivalent pipeline (DIA-NN 1.9.2 or Skyline) → protein-level intensities → log-transform + quantile normalisation → 5-fold cross-validated logistic regression with the 8 published proteins as features, labels = iRBD-converter vs. iRBD-non-converter at 7-year follow-up. Primary success = 5-fold CV AUC ≥ 0.85 (the published Hällqvist 7-year AUC is ≈ 1.0; we allow margin for spectra → intensity pipeline divergence).
H2 (secondary — individual-protein hazard ratios reproduce): Each of the 8 proteins, modeled univariately in a Cox proportional-hazards model on time-to-conversion, shows the same sign of hazard ratio as published (Hällqvist Supplementary Table 3). Concordance metric = 8/8 sign agreement; loose acceptance = ≥ 6/8.
H3 (secondary — panel beats clinical-only baseline): Adding the 8-protein panel to a clinical-baseline Cox model (age + sex + MoCA + UPSIT) improves time-dependent AUC at 5 years by ΔAUC > 0.05 with paired bootstrap CI excluding 0. The clinical baseline serves as the Venet-style floor.
H4 (secondary — out-of-cohort signature alignment to UK Biobank Olink): Of the 8 panel proteins, 6 are on the UK Biobank Olink Explore 1536 panel. We test whether the directionality (HR sign) reported for these 6 proteins in the Gan/You 2025 UKB Olink incident-PD analysis (Nat Aging 5:642) matches the Hällqvist signs. Concordance = 6/6 expected; loose acceptance ≥ 4/6 with binomial p < 0.05 vs. chance 0.5.
H5 (secondary — sub-panel decomposition): Decompose the 8-panel into 3 functional sub-panels: (a) inflammation / complement: ICAM1, C3, SERPING1 (b) proteostasis: HSPA5, GRN (c) lipid / cell signaling: PTGDS, DKK3, MASP2 Test whether any single sub-panel achieves AUC > 0.75 on its own — i.e., is the predictive signal carried by one of three functional axes or distributed?
A negative-leaning result on H1 (cross-pipeline AUC < 0.7) would be a major methodological caveat for the field and would imply that quantitative biomarker panels are sensitive to MS pipeline choice — itself an informative finding given the rapid uptake of the Hällqvist panel in trial design.
The research question comes from the topic's current research brief. All attempts at a topic share it; earlier attempts may have started from an earlier wording.