Campaign run · Parkinson's disease

parkinson-multimodal-spatial-proteomics-r1

PDPlanned, no test completedAttempt 1 of 3 at this topic

Does a MOFA+ (Multi-Omics-Factor-Analysis) joint embedding of three modalities of PD substantia-nigra data — Martirosyan 2024 snRNA-seq + Visium (GSE243639), Ma 2025 GeoMx spatial (PMC12322057), and Zhu 2024 LC-MS/MS DLPFC proteomics (PRIDE PXD030142) — reveal factor(s) that ONLY appear when all three modalities are jointly modelled, and that are unrecoverable from any pairwise integration?

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

Multi-modal integration has become a default expectation in PD research, but the value-add of going from 2-modal to 3-modal is rarely tested with a clean ablation. Pairwise integrations in PD exist: snRNA × Visium (Martirosyan 2024); snRNA × proteomics (Zhu 2024); spatial × CosMx (Goralski 2024). Joint 3-modal MOFA+ on PD-SN has not been published. This OmiCairn run pre-registers the ablation that asks whether the third modality is necessary or decorative.

Hypotheses (pre-registered):

H1 (primary — all-modalities factor exists): ≥ 1 MOFA+ factor explains > 5% variance in EACH of the three modalities simultaneously, AND is associated with PD diagnosis (per-donor-group Wilcoxon p < 0.05). Pre-registered name: "all-modalities factor".

H2 (secondary — proteomics necessity ablation): Removing the proteomics modality and re-fitting MOFA+ produces a closest-matching factor (max absolute loading correlation with the H1 factor) whose explained variance in the spatial modality drops by ≥ 30 percentage points. Proteomics is NECESSARY for the joint factor, not nice-to-have.

H3 (secondary — top-loaded gene enrichment): Top-100 loaded genes of the all-modalities factor are enriched (q < 0.05 hypergeometric) for the union of: Goralski 2024 LAMDA cortical signature genes, AND Hemedan 2024 Boolean-PD "key-regulator" gene list.

H4 (secondary — modality-balance check): No single modality contributes > 60% of the explained variance summed across the H1 factor (otherwise the "all-modalities" label is misleading).

H5 (secondary — pairwise comparison): Repeat the analysis with three pairwise MOFA+ models — (snRNA + Visium), (snRNA + proteomics), (Visium + proteomics). Test whether any pairwise model recovers a factor with ≥ 0.7 absolute loading correlation to the H1 3-modal factor. If yes, the 3-modal claim is weaker than headline. If no, 3-modal is necessary.

Null payoff. A null all-modalities factor (H1: no factor >5% variance in all three modalities, or no PD association) means PD SN biology is dominated by the strongest single modality (probably snRNA-seq) and multi-omics doesn't add. Canonical ablation answer the field has been asking.

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	MOFA+ on snRNA+Visium+proteomics yields >=1 factor with >5% variance in each modality AND PD-associated (Wilcoxon p<0.05).	Not runIn the explorer
H2Pre-registered	Removing proteomics drops the matched factor's Visium explained variance by >=30 pp (permutation p<0.05).	Not runIn the explorer
H3Pre-registered	Top-100 H1-factor genes enriched for LAMDA and/or Hemedan Boolean-PD regulators (hypergeometric q<0.05).	Not runIn the explorer
H4Pre-registered	No single modality contributes >60% of H1-factor explained variance.	Not runIn the explorer
H5Pre-registered	No pairwise MOFA+ model recovers a factor with loading \|r\|>=0.7 to the H1 factor.	Not runIn the explorer