Campaign run · Parkinson's disease

parkinson-cellchat-immune-axis-r3

PDCompleted the pipelineAttempt 3 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?

2111

Supported 2
Not supported 1
Not testable (data) 1
Not tested (run did not execute) 1

Open the final report (PDF)This run in the hypothesis explorer

Status

How far it got: Completed the pipeline
Tested at least one hypothesis and reached the multi-agent review stage. This shows the run went through the whole pipeline, not that its work passed a quality bar.
Hypotheses: 5 nominated; 4 evaluated; 1 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: Success. 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-up in both PBMC CD8+T->monocyte (GSE223138) and brain CD8+T->microglia (Ma 2025 SN; fallback Fullard), permutation p<0.01	SupportedIn the explorer
Evidence (verbatim from the run outputs) H1 SUPPORTED: 9 L-R pairs are shared between PBMC CD8+T→monocyte and brain CD8+T→CNS macrophage PD-upregulated top-100 lists Adjudication note Rule met (9 pairs; p<1/10,000). Caveats: brain arm = Fullard non-SN fallback (no SN tissue); NATMI substituted for LIANA rank_aggregate (segmentation fault); 1,000 cells/donor subsample; hardcoded donor-disease fallback mapping.
H2Pre-registered	Ligands/receptors of shared pairs enriched (q<0.05) among 28 Hong 2025 MR-implicated immune genes	Not supportedIn the explorer
Evidence (verbatim from the run outputs) Decision: H2 NOT SUPPORTED (p = 0.346). Adjudication note Only 18 genes; run notes low power (OR=2.56, CI 0.058-18.0).
H3Pre-registered	Per-donor peripheral signature scores correlate with brain T-cell module scores (peripheral-foreshadow)	Not testableIn the explorer
Evidence (verbatim from the run outputs) Status: INAPPLICABLE. Per the scope stage (data profile), the parkinson-tcell-foothold cross-workspace results record contains only atlas-level summary statistics Adjudication note No per-donor brain vector available.
H4Pre-registered	Reverse direction (monocyte->CD8+T, microglia->CD8+T) does NOT reach H1 threshold (<5 pairs, perm p>=0.05): direction-specificity	SupportedIn the explorer
Evidence (verbatim from the run outputs) "H4_reverse_permutation_p": 0.0528, Adjudication note DISCREPANCY: pre-registered rule (reverse count <5 AND p>=0.05) is literally met (count=4, p=0.0528), but analysis/report label it 'BORDERLINE'/'inconclusive', apparently misreading the p>=0.05 clause. Substantively weak: reverse p is near-significant. Reviewer may prefer INCONCLUSIVE.
H5Pre-registered	Per-method shared-pair counts (CellPhoneDB, NATMI, scTalk, CellChat, Connectome) within +/-2 of LIANA consensus	Not runIn the explorer
Evidence (verbatim from the run outputs) All 5 H5 "method" counts use NATMI expr_prod columns with different sorting — not true independent methods. Adjudication note Run/report call H5 SUPPORTED (max deviation 0), but independent methods were never run (LIANA rank_aggregate segfault) — proxy-only, technical failure.

Final report

Title (as written by the system)

Nine concordant peripheral-brain CD8+ T cell ligand-receptor pairs in Parkinson's disease: a blood-as-foreshadow analysis

Main conclusion

Nine PD-upregulated CD8+ T to myeloid L-R pairs were shared between PBMC and non-SN brain axes (observed 9 vs null mean 1.39, Delta = 7.607, p < 1/10,000; H1 supported). MR-gene enrichment was not significant (H2: OR = 2.56, p = 0.346, underpowered). Direction-specificity was borderline (H4: reverse p = 0.053). H5 robustness was met, but the methods were not truly independent, and PD specificity remains unestablished.

Report titles are the system's own and can state a result more strongly than the report's verdicts support. Read the main conclusion and the verdicts with it. The main conclusion was written during release review and keeps the report's own numbers and verdicts.

The PDF is published exactly as released. It may call itself a “paper”, call the system's internal multi-agent review “peer review”, and cite internal stage folders by number.

Open the final report (PDF, 274 KB)

All 3 attempts at this topic

parkinson-cellchat-immune-axis-r1Planned, no test completed
parkinson-cellchat-immune-axis-r2Stopped before planning
parkinson-cellchat-immune-axis-r3Completed the pipeline Report

Attempts are numbered in launch order. A topic was relaunched when an earlier attempt stopped or was superseded.