Campaign run · Parkinson's disease

parkinson-multimodal-spatial-proteomics-r2

PDStopped before planningAttempt 2 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?

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Stopped before writing any hypotheses: a dry-run test, a launch superseded by an immediate relaunch, a usage limit or a process failure.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 Runs in this group are dry-run tests, launches superseded by an immediate relaunch, runs that hit a usage limit, or one process failure.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

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.