Campaign run · Parkinson's disease
parkinson-tcell-foothold-r1
The question is whether the transcriptomic footprint of the Ma-2025 T-cell signature (the genes co-expressed in the clonally expanded CD8+ population) can be detected in those four independent atlases, in a deconvolution-inferred T-cell or lymphocyte cluster, without TCR ground truth.
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Stopped before writing any hypotheses: a dry-run test, a launch superseded by an immediate relaunch, a usage limit or a process failure.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 Runs in this group are dry-run tests, launches superseded by an immediate relaunch, runs that hit a usage limit, or one process failure.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
Halted. The run recorded a final status of halted: it was closed without being marked done. A halted run can still have tested hypotheses and written a final report.
- Census class
Early stop. 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
Ma, J., Al-Dalahmah, O., Goldman, J.E., Sulzer, D., Sims, P.A. et al. (Nat Commun s41467-025-62478-3, 2025; PMC12322057) reported spatially resolved adaptive immunity in Parkinson's disease substantia nigra: combined snRNA-seq + 10x Visium + scTCR-seq across 44 donors (13 PD + 15 ctrl SN; 10 PD + 8 ctrl cingulate; 265,284 nuclei + 10 donors with Visium) identified clonally expanded CD8+ T cells whose TCRs share homology with α-synuclein peptides and which spatially co-localise with CD44+ reactive astrocytes in PD SN.
The Ma 2025 result depends on rare TCR-seq data, which the Kamath 2022 (GSE178265), Wang 2024 (GSE184950), Adams 2024 (GSE193688) and Fullard 2024 multi-region atlases do not have. The question is whether the transcriptomic footprint of the Ma-2025 T-cell signature (the genes co-expressed in the clonally expanded CD8+ population) can be detected in those four independent atlases, in a deconvolution-inferred T-cell or lymphocyte cluster, without TCR ground truth.
Hypotheses (pre-registered):
H1 (primary — transcriptomic footprint replicates in independent PD snRNA-seq atlases): The Ma 2025-defined T-cell signature (extracted from Supplementary Data of PMC12322057 — the top-50 differentially expressed genes in the clonally expanded CD8+ population vs. all other immune nuclei in PD SN) is scored per cell in T-cell / lymphocyte clusters of:
- Kamath 2022 (GSE178265) SNpc + caudate
- Wang 2024 (GSE184950) SNpc
- Adams 2024 (GSE193688) SN
- Fullard 2024 SNpc + M1 (CELLxGENE d5d0df8f-...) and tested for PD-vs-control per-donor pseudobulk differential at FDR<0.1. At least 3 of 4 atlases show log2FC > 0 in the T-cell-module score in the PD direction.
H2 (secondary — region specificity within multi-region atlas): Within the Fullard atlas (the only multi-region atlas in the panel), the T-cell-module signal is significantly higher in SNpc + cingulate-like cortical regions than in DMNX (Braak 1, vagal-driven, no expected adaptive immune component) or V1 (Braak 6, late-stage, no expected ongoing immune infiltration). Pre-registered ranking: SNpc > M1 > V1 ≈ DMNX. Spearman ρ on rank vs. signature score > 0.5, permutation p < 0.05.
H3 (secondary — T-cell-module × DA-loss covariation): At the donor level, in Kamath / Wang / Adams / Fullard atlases, the T-cell-module pseudobulk score is positively correlated with the AGTR1+ DA-loss score (computed identically to parkinson-da-vulnerability proposal): donors with more T-cell signal also have more vulnerable- DA loss. Spearman ρ > 0.3, permutation p < 0.05 in ≥ 2 of 4 atlases.
H4 (secondary — astrocyte co-localisation in spatial slabs): Where Visium-spatial data is available (Martirosyan A5, Ma 2025 itself), spatial spots scoring high for the T-cell module are also enriched for CD44+ / GFAP-high reactive astrocyte markers (Ma 2025's reported co-localisation), with Spearman ρ > 0.3 on per-spot z-scored module scores.
H5 (secondary — non-α-syn-homology bound — negative control): We pre-register a non-PD-relevant T-cell sub-signature (a generic exhaustion module: PDCD1, HAVCR2, LAG3, TOX, TIGIT) as a negative control. The exhaustion module should NOT show preferential PD enrichment (this signal is canonical to tumor immunology and PD T cells are not exhausted in the same way). A positive enrichment of the exhaustion module would suggest the H1 signal is a non-specific "T cell present" signal rather than a PD-specific clonally-expanded program.
A null result on H1 is informative: it would mean that without TCR-seq ground truth, the clonal-expansion signal in Ma 2025 is not detectable from gene expression alone — calling into question any retrospective inference of adaptive immunity from existing PD snRNA-seq atlases.
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.