Campaign run · Parkinson's disease

parkinson-cellchat-immune-axis-r1

PDPlanned, no test completedAttempt 1 of 3 at this topic

Do LIANA-py (CellChat-equivalent consensus) inferred ligand-receptor (L-R) communications between Hong 2025 peripheral-blood CD8+ T cells (GEO GSE223138) and Fullard brain microglia mirror — at the L-R pair level — the brain-internal CD8+T → microglia communications inferred by Ma 2025 (PMC12322057), thus identifying a "blood-as-foreshadow-of-brain" set of peripheral biomarker ligands?

Not tested (run did not execute) 5

This run in the hypothesis explorer

Status

How far it got: Planned, no test completed
Wrote pre-registered hypotheses with decision rules, but no hypothesis test was completed. Its hypotheses are listed as not tested (run did not execute).
Hypotheses: 5 nominated; 0 evaluated; 5 not tested because the run did not execute them.
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: 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

Hong 2025 (npj Parkinson's 11) reported 28 immune-cell-specific PD risk genes from OneK1K + IPDGC + GSE223138 multi-omic integration. Ma 2025 (Nat Commun 16) characterised brain-side CD8+ T-cell × microglia communications via SN scRNA + scTCR-seq. The two cell-type-communication signatures have not been compared at the L-R pair level. If peripheral L-Rs echo brain L-Rs, the peripheral signal could be used as a foreshadow blood biomarker; if they diverge, peripheral-blood-as-PD-biomarker biology is decoupled from the brain-immune axis. Either outcome is informative with strong biomarker implications.

Hypotheses (pre-registered):

H1 (primary — L-R pair concordance): ≥ 5 ligand-receptor pairs are inferred as PD-up-regulated in BOTH the peripheral CD8+T → blood-monocyte direction (Hong 2025) AND the brain CD8+T → microglia direction (Ma 2025), with concordant sign of dysregulation. Permutation null p < 0.01 (10,000 random L-R subsets).

H2 (secondary — Hong-MR-gene enrichment): The shared L-R pairs are enriched (q < 0.05 hypergeometric) for ligands or receptors whose genes appear on the Hong 2025 MR-implicated immune-gene list (FDFT1, CTSB, ARSA, HLA-DQA1, and 24 others reported in Hong 2025 Table 2).

H3 (secondary — peripheral-foreshadow correlation): A "peripheral CD8+T signature score" computed from Hong 2025 PBMC data using the 28 MR-implicated immune genes rank-correlates (Spearman ρ > 0.3, nominal p < 0.05) with the v1 parkinson-tcell-foothold per-donor brain T-cell-module score at the disease-stage level (early vs. late PD).

H4 (secondary — direction-specific dropout): Inferring CD8+T → monocyte (PBMC) and microglia → CD8+T (brain) — the reverse-direction pairs — should NOT show the same H1 enrichment (control: PD signals are in the CD8+T → myeloid direction, not the reverse).

H5 (secondary — method-consensus robustness): Repeat the L-R inference with three methods (CellPhoneDB, NATMI, scTalk) and confirm the H1 shared-pair count is within ±2 of the LIANA consensus result. (LIANA-py provides this consensus natively.)

Null payoff. If peripheral and brain L-R signatures diverge (H1: 0-3 shared pairs), peripheral-blood-as-PD-biomarker biology is decoupled from the brain-immune axis — informative, with strong implications for blood-test development.

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.

Hypotheses and verdicts

Each hypothesis was written with its decision rule before any analysis (or, for on-the-fly hypotheses, recorded during execution). AI adjudication agents applied that rule to the run's latest outputs and quoted the evidence verbatim. Where the data did not meet the rule, the verdict follows the data, even if the run's own label or report claimed support.

Each hypothesis as pre-registered (a condensed statement with its decision rule), the adjudicated verdict, the verbatim evidence and the adjudicator's note.
ID	Hypothesis and decision rule	Verdict
H1Pre-registered	>=5 L-R pairs PD-upregulated in both peripheral CD8+T->monocyte (GSE223138 PBMC) and brain CD8+T-like->CNS macrophage (Fullard 2024), permutation p<0.01.	Not runIn the explorer
Evidence (verbatim from the run outputs) API Error: The socket connection was closed unexpectedly. Adjudication note EXECUTE stage 3 terminated on a connection error before writing results (no results/analysis records); run halted and was never re-executed.
H2Pre-registered	Shared L-R pairs enriched for Hong 2025 28 MR-implicated immune genes (BH q<0.05, hypergeometric).	Not runIn the explorer
Evidence (verbatim from the run outputs) API Error: The socket connection was closed unexpectedly. Adjudication note EXECUTE stage 3 terminated on a connection error before writing results (no results/analysis records); run halted and was never re-executed.
H3Pre-registered	Per-donor peripheral CD8+T MR-gene score rank-correlates with brain T-cell module score (Spearman rho>0.3, p<0.05).	Not runIn the explorer
Evidence (verbatim from the run outputs) API Error: The socket connection was closed unexpectedly. Adjudication note EXECUTE stage 3 terminated on a connection error before writing results (no results/analysis records); run halted and was never re-executed. Plan already expected H3 likely INAPPLICABLE (no donor overlap between PBMC and post-mortem brain).
H4Pre-registered	Direction-specificity control: reverse-direction inference yields fewer shared pairs and permutation p>=0.05.	Not runIn the explorer
Evidence (verbatim from the run outputs) API Error: The socket connection was closed unexpectedly. Adjudication note EXECUTE stage 3 terminated on a connection error before writing results (no results/analysis records); run halted and was never re-executed.
H5Pre-registered	Method-consensus robustness: LIANA consensus shared-pair count within +/-2 of CellPhoneDB, NATMI, scTalk counts.	Not runIn the explorer
Evidence (verbatim from the run outputs) API Error: The socket connection was closed unexpectedly. Adjudication note EXECUTE stage 3 terminated on a connection error before writing results (no results/analysis records); run halted and was never re-executed.