[ { "id": "alzheimer-apoe4-microglia-ldam-r1/H1", "run": "alzheimer-apoe4-microglia-ldam-r1", "disease": "AD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "APOE4/4 vs APOE3/3 microglial pseudobulk: >=2/4 LDAM markers up AND >=2/3 DAM2 markers down (FDR<0.05) at matched Braak (SEA-AD primary, Morabito replication).", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "The H1 decision rule required ≥2 LDAM markers upregulated and ≥2 DAM2 markers downregulated at FDR<0.05; neither criterion was met. H1 is therefore not supported.", "adjudication_note": "0/7 markers FDR<0.05; DAM2 trended UP. Tested only as binary APOE4 carrier (n=25) vs non-carrier (n=59) because CellxGene SEA-AD lacks e4/4 vs e3/3 genotype; bootstrap log2FC instead of DESeq2; Morabito replication impossible (no APOE column). Strict reading could call this NOT_TESTED_DATA (diluted proxy contrast). Knowledge-graph status = refuted.", "report_url": "/assets/reports/alzheimer-apoe4-microglia-ldam-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-apoe4-microglia-ldam-r1/H2", "run": "alzheimer-apoe4-microglia-ldam-r1", "disease": "AD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "Per-donor LDAM/DAM ratio positively associated with tau (Braak) after adjusting for amyloid; beta_tau>0, p<0.05, 95% CI excludes 0.", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "The partial regression coefficient for Braak stage was β_tau=+0.031 (95% bootstrap CI: −0.007 to +0.069; p=0.143; Fig. 4c)", "adjudication_note": "Report: 'H2 is therefore not supported.' Direction positive; plan rated H2 adequately powered (MDE r~0.29) but report says post hoc n~290 needed for observed r=0.162; age covariate dropped (categorical bins). Knowledge-graph last status = inconclusive.", "report_url": "/assets/reports/alzheimer-apoe4-microglia-ldam-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-apoe4-microglia-ldam-r1/H3", "run": "alzheimer-apoe4-microglia-ldam-r1", "disease": "AD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Monotonic APOE dose-response: LDAM score e3/3 < e3/4 < e4/4 and DAM2 e3/3 > e3/4 > e4/4 (Jonckheere-Terpstra, Braak-controlled).", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "Because the CellxGene object provides only binary carrier status, the test reduces to a two-group comparison equivalent to Mann-Whitney U.", "adjudication_note": "Three-genotype dose-response untestable (binary APOE4 only). Proxy 2-group, Braak-UNadjusted test: LDAM p=0.006 (Bonf. 0.012), DAM2 p=0.887. Report relabels this as 'exploratory, not pre-registered' although H3 is in the PLAN-stage hypothesis list. Knowledge-graph status = supported (discrepancy). If proxy counted as a test: at most PARTIALLY_SUPPORTED.", "report_url": "/assets/reports/alzheimer-apoe4-microglia-ldam-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-apoe4-microglia-ldam-r1/OTF1", "run": "alzheimer-apoe4-microglia-ldam-r1", "disease": "AD", "hypothesis_id": "OTF1", "origin": "on_the_fly", "hypothesis": "APOE expression itself is elevated in LDAM-state microglia in SEA-AD (APOE4 autocrine feedback loop).", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "upregulates APOE transcription.", "adjudication_note": "Raised in EXECUTE stage 2 (marked cheap to test); no later execute stage; data available but never run.", "report_url": "/assets/reports/alzheimer-apoe4-microglia-ldam-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-apoe4-microglia-ldam-r1/OTF2", "run": "alzheimer-apoe4-microglia-ldam-r1", "disease": "AD", "hypothesis_id": "OTF2", "origin": "on_the_fly", "hypothesis": "In e4/e4 homozygous donors (Synapse syn64410371 metadata) the LDAM/DAM2 shift is larger than in heterozygotes and the H1 rule would pass.", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "Accessing fine-grained ε4/4 vs ε3/3 homozygous genotype from the SEA-AD Synapse release (syn64410371) and re-running the H1 pseudobulk DE contrast", "adjudication_note": "Listed only as a next step; fine-grained genotype absent from the fetched CellxGene object and the Synapse metadata was never fetched.", "report_url": "/assets/reports/alzheimer-apoe4-microglia-ldam-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-apoe4-microglia-ldam-r1/OTF3", "run": "alzheimer-apoe4-microglia-ldam-r1", "disease": "AD", "hypothesis_id": "OTF3", "origin": "on_the_fly", "hypothesis": "A linear mixed model with categorical age bins as random effects would recover a significant beta_tau for H2 in the same 84 donors.", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "with the same 84 donors.", "adjudication_note": "Never run; data available.", "report_url": "/assets/reports/alzheimer-apoe4-microglia-ldam-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-gwas-snatac-celltype-r1/H1", "run": "alzheimer-gwas-snatac-celltype-r1", "disease": "AD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "Of top-75 AD GWAS loci, microglia-dominant snATAC fraction exceeds p0=0.25 (>=25 loci, binomial) AND SPI1 motif accessibility is the top predictor of microglial dominance.", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "Under that denominator, the observed proportion is 13/75=17.3%, and the binomial test against p₀=0.25 gives p≈0.87 (FAIL).", "adjudication_note": "Criterion 1 fails under pre-registered n=75 denominator (only 33/75 loci had any peak); among 33 testable loci 13 MG-dominant, binomial p=0.048 (post hoc conditioning). Criterion 2 (SPI1) untestable: JASPAR/FIMO unavailable, logistic proxy circular/non-convergent. OmiCairn stage 4 analysis labelled 'PARTIAL' and knowledge-graph status = supported (discrepancy; code review & report call it FAIL).", "report_url": "/campaign/runs/alzheimer-gwas-snatac-celltype-r1/report/", "report_kind": "html" }, { "id": "alzheimer-gwas-snatac-celltype-r1/H2", "run": "alzheimer-gwas-snatac-celltype-r1", "disease": "AD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "Microglial GWAS-overlapping peak accessibility peaks at DAM/mid-disease stage vs both homeostatic and late stages (both contrasts p<0.05, CI excl. 0).", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "GWAS-overlapping peak accessibility was not stage-dependent (early vs late Δ=−0.008, 95% CI −0.023 to 0.007, p=0.881), refuting H2.", "adjudication_note": "Late-stage numerically higher (opposite). DAM-marker Stage2>Stage1 contrast 'significant' but flagged by code review as bootstrap collapse at 3-5 donors/group. Only 20 Morabito donors (plan: underpowered, d>=1.45); SEA-AD fallback not run (Synapse auth). Knowledge-graph nodes: one inconclusive, one refuted.", "report_url": "/campaign/runs/alzheimer-gwas-snatac-celltype-r1/report/", "report_kind": "html" }, { "id": "alzheimer-gwas-snatac-celltype-r1/H3", "run": "alzheimer-gwas-snatac-celltype-r1", "disease": "AD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Exploratory: secondary compartment of GWAS loci in excitatory-neuron peaks; rank order microglia > excitatory neurons > oligodendrocytes ~ astrocytes.", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "Number of GWAS loci where each cell type is dominant (MG: 13, ASC: 7, EX: 3, ODC: 2; 8 below accessibility floor).", "adjudication_note": "UNCERTAIN: no pre-registered threshold and the planned chi-square/pairwise Fisher tests were never run; verdict is descriptive only (observed order MG>ASC>EX>ODC, EX not second). Defensible alternative: INCONCLUSIVE.", "report_url": "/campaign/runs/alzheimer-gwas-snatac-celltype-r1/report/", "report_kind": "html" }, { "id": "alzheimer-gwas-snatac-celltype-r1/OTF1", "run": "alzheimer-gwas-snatac-celltype-r1", "disease": "AD", "hypothesis_id": "OTF1", "origin": "on_the_fly", "hypothesis": "Proportion of microglia-dominant loci exceeds the mean proportion for non-microglial cell types.", "verdict": "Supported", "outcome": "supported", "outcome_class": "positive", "evidence_quote": "This CI excludes 0, supporting directional microglial enrichment among loci with detectable accessibility.", "adjudication_note": "Delta=0.273, 95% CI [0.071, 0.485], p=0.004, but only among 33/75 testable loci; report notes compositional non-independence and that the stricter permutation-null comparison is not significant (Delta=0.029, p=0.483).", "report_url": "/campaign/runs/alzheimer-gwas-snatac-celltype-r1/report/", "report_kind": "html" }, { "id": "alzheimer-gwas-snatac-celltype-r1/OTF2", "run": "alzheimer-gwas-snatac-celltype-r1", "disease": "AD", "hypothesis_id": "OTF2", "origin": "on_the_fly", "hypothesis": "GWAS-linked microglial circuits peak at late disease (Stage 5-6) rather than mid-disease (sustained late-inflammatory phenotype).", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "The SEA-AD atlas [9]—84 donors spanning the full severity spectrum with paired snATAC-seq and quantitative neuropathology—is the appropriate resource to resolve H2 definitively.", "adjudication_note": "Raised twice (stages 2 and 4). Morabito early-vs-late CI includes 0; SEA-AD snATAC blocked by Synapse authentication.", "report_url": "/campaign/runs/alzheimer-gwas-snatac-celltype-r1/report/", "report_kind": "html" }, { "id": "alzheimer-gwas-snatac-celltype-r1/OTF3", "run": "alzheimer-gwas-snatac-celltype-r1", "disease": "AD", "hypothesis_id": "OTF3", "origin": "on_the_fly", "hypothesis": "Fine-mapped credible sets (+/-5-50 kb) would recover more loci than lead-SNP overlap and may strengthen microglial enrichment.", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "**Use fine-mapped credible sets** from Bellenguez 2022 rather than lead SNPs.", "adjudication_note": "Run halted (orphaned) at claim-review stage 7 before any follow-up execute; credible sets are public.", "report_url": "/campaign/runs/alzheimer-gwas-snatac-celltype-r1/report/", "report_kind": "html" }, { "id": "alzheimer-ligrec-braak-breakdown-r1/H1", "run": "alzheimer-ligrec-braak-breakdown-r1", "disease": "AD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "C1Q-C3-CR3, SPP1 and CXCL10-CXCR3 are among the top-10 disrupted L-R axes in AD PFC, each with positive monotone Braak slope (p<0.05, CI excl. 0).", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "H1 therefore fails on all three pre-registered sub-criteria.", "adjudication_note": "Final EXECUTE stage 9: C3-ITGAM rank 257 (p=0.565), SPP1-ITGA9 rank 45 and DOWN, CXCL10-CXCR3 absent from CellChatDB. Braak-monotone component untestable (no Braak in GSE157827; binary AD-vs-NC only). Global donor-label permutation p=0.494; report calls it 'an underpowered null result, not a powered negative' -> some may prefer INCONCLUSIVE. Graph H1 nodes last status inconclusive; stage 9 graph update = refutes.", "report_url": "/assets/reports/alzheimer-ligrec-braak-breakdown-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-ligrec-braak-breakdown-r1/H2", "run": "alzheimer-ligrec-braak-breakdown-r1", "disease": "AD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "Genes of disrupted L-R pairs (Braak III-IV or AD-vs-control) are enriched in top-20 AD GWAS locus genes (hypergeometric p<0.05, OR CI excl. 1).", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "H2 as pre-registered (direct overlap) is therefore untestable with this resource", "adjudication_note": "OmiCairn/report label it NOT SUPPORTED (OR=0.0, CI [0, 3.59], p=1.0) but only 2 GWAS genes are in the 305-gene CellChatDB background, i.e. a structurally degenerate test; Braak III-IV stratum also unavailable. Alternative: INCONCLUSIVE. Graph = refuted.", "report_url": "/assets/reports/alzheimer-ligrec-braak-breakdown-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-ligrec-braak-breakdown-r1/H3", "run": "alzheimer-ligrec-braak-breakdown-r1", "disease": "AD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Exploratory: disrupted-axis intensity across EC, hippocampus, PFC tracks tau-spread order (Spearman rho>=0, p<0.05; needs SEA-AD multi-region).", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "could not be tested in this study because GSE157827 covers only PFC and the SEA-AD multi-region atlas (Synapse syn64410371; [19]) was not fetched for this analysis", "adjudication_note": "Single-region atlas; multi-region data never fetched.", "report_url": "/assets/reports/alzheimer-ligrec-braak-breakdown-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-ligrec-braak-breakdown-r1/OTF1", "run": "alzheimer-ligrec-braak-breakdown-r1", "disease": "AD", "hypothesis_id": "OTF1", "origin": "on_the_fly", "hypothesis": "LAMA2->integrin (microglia->astrocyte) disruption reflects pericellular-matrix change and tracks Braak stage as microglia shift to DAM.", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "this should be tested in SEA-AD where continuous neuropathology scores are available", "adjudication_note": "Needs Braak-resolved data; SEA-AD never fetched.", "report_url": "/assets/reports/alzheimer-ligrec-braak-breakdown-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-ligrec-braak-breakdown-r1/OTF2", "run": "alzheimer-ligrec-braak-breakdown-r1", "disease": "AD", "hypothesis_id": "OTF2", "origin": "on_the_fly", "hypothesis": "JAM2->ITGB1 (endothelial->excitatory neuron) elevation reflects Braak-dependent BBB breakdown.", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "in a multi-donor dataset with both BBB markers and Braak staging", "adjudication_note": "No Braak-staged dataset used; JAM2->ITGB1 only nominal p=0.021 uncorrected in GSE157827.", "report_url": "/assets/reports/alzheimer-ligrec-braak-breakdown-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-ligrec-braak-breakdown-r1/OTF3", "run": "alzheimer-ligrec-braak-breakdown-r1", "disease": "AD", "hypothesis_id": "OTF3", "origin": "on_the_fly", "hypothesis": "Reformulated H2: NicheNet downstream targets of top disrupted L-R pairs are enriched in GWAS-locus regulatory modules.", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "This reformulation of H2 is the principal actionable next step.", "adjudication_note": "Never run (different framework needed); data available.", "report_url": "/assets/reports/alzheimer-ligrec-braak-breakdown-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-ligrec-braak-breakdown-r1/OTF4", "run": "alzheimer-ligrec-braak-breakdown-r1", "disease": "AD", "hypothesis_id": "OTF4", "origin": "on_the_fly", "hypothesis": "Relative ranking of ECM vs complement/SPP1 axes is real (Delta=0.662, p=0.001) but absolute disruption needs larger n (SEA-AD).", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "SEA-AD with n > 400 donors would test this definitively.", "adjudication_note": "Present only in an EXECUTE-stage graph update (not merged into the knowledge graph); larger cohort never fetched.", "report_url": "/assets/reports/alzheimer-ligrec-braak-breakdown-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-ligrec-braak-breakdown-r1/OTF5", "run": "alzheimer-ligrec-braak-breakdown-r1", "disease": "AD", "hypothesis_id": "OTF5", "origin": "on_the_fly", "hypothesis": "MDK->ALK (endothelial->endothelial, log2FC -1.90) is a novel AD-associated loss of vascular neuroprotective signalling.", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "MDK is a heparin-binding growth factor with neuroprotective roles", "adjudication_note": "Only in stage 9 graph-update record (not in knowledge graph); flagged cheap to test, never followed up.", "report_url": "/assets/reports/alzheimer-ligrec-braak-breakdown-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-ligrec-braak-breakdown-r1/OTF6", "run": "alzheimer-ligrec-braak-breakdown-r1", "disease": "AD", "hypothesis_id": "OTF6", "origin": "on_the_fly", "hypothesis": "SEMA5A->PLXNA3/PLXNA1 (microglia->astrocyte/neuron) reduction reflects axon-guidance disruption contributing to synaptic pruning deficits.", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "Semaphorin 5A is implicated in neural circuit refinement", "adjudication_note": "Only in stage 9 graph-update record (not in knowledge graph); never followed up.", "report_url": "/assets/reports/alzheimer-ligrec-braak-breakdown-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-rorb-ec-vulnerability-r1/H1", "run": "alzheimer-rorb-ec-vulnerability-r1", "disease": "AD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "RORB+ vs RORB- EC excitatory neurons: CACNA1C or CACNA1D up AND CALB1 or PVALB down (BH-FDR<0.05), sign reproduced in second atlas.", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "**H1 verdict: NOT SUPPORTED.** No gene reaches BH-FDR < 0.05.", "adjudication_note": "Latest (008, GSE147528 primary, 2,009 RORB+ cells/10 donors): CACNA1C/D opposite sign, CIs include 0; PVALB log2FC -1.18 CI excludes 0 but FDR 0.865 (t-test NaN issue). Report calls it a powered negative. Atlas roles swapped vs plan (GSE138852 had only 16 RORB+ cells).", "report_url": "/assets/reports/alzheimer-rorb-ec-vulnerability-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-rorb-ec-vulnerability-r1/H2", "run": "alzheimer-rorb-ec-vulnerability-r1", "disease": "AD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "ISR module score in RORB+ EC neurons increases with Braak stage (slope>0, p<0.05, CI excl. 0), preceding RORB+ loss.", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "failing the pre-registered H2 criterion of a positive slope at p < 0.05", "adjudication_note": "Slope -0.006/Braak (CI [-0.018, +0.002], p=0.213), opposite direction; n=10 donors, Braak 0/2/6 only (plan: borderline power).", "report_url": "/assets/reports/alzheimer-rorb-ec-vulnerability-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-rorb-ec-vulnerability-r1/H3", "run": "alzheimer-rorb-ec-vulnerability-r1", "disease": "AD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Exploratory: one vulnerability program (excitability, ISR/proteostasis, mitochondrial) separates RORB+ from RORB- more strongly than others (Cohen's d, >0.3 SD).", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "An exploratory excitability gene module score is positive in direction (d = +0.269) but spans zero at the donor level of inference (approximate CI [−0.362, +0.900])", "adjudication_note": "Excitability had the largest |d| but below the 0.3 SD benchmark; cell-level bootstrap CIs anti-conservative, donor-level CI spans 0. Knowledge-graph node ('excitability module higher') = supported (discrepancy).", "report_url": "/assets/reports/alzheimer-rorb-ec-vulnerability-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-rorb-ec-vulnerability-r1/H4", "run": "alzheimer-rorb-ec-vulnerability-r1", "disease": "AD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "Exploratory: RORB+ EC excitatory subcluster recoverable at Leiden 0.6-1.2 in both GSE138852 and GSE147528 with >80% consistent assignment.", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "This is a **Tier-A negative finding**: the primary atlas does not contain enough RORB+ neurons for valid pseudobulk DE", "adjudication_note": "GSE138852: 16 RORB+ nuclei, 1/6 pools >=5 cells (pre-registered Tier-A negative). Leiden resolution sweep never run (OMP crash); threshold-based annotation used. Knowledge-graph status = refuted.", "report_url": "/assets/reports/alzheimer-rorb-ec-vulnerability-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-rorb-ec-vulnerability-r1/OTF1", "run": "alzheimer-rorb-ec-vulnerability-r1", "disease": "AD", "hypothesis_id": "OTF1", "origin": "on_the_fly", "hypothesis": "ISR module is LOWER in RORB+ than RORB- EC neurons (at all Braak stages), counter to the ISR-driven vulnerability model.", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "The ISR module score was lower in RORB+ than RORB- neurons (d = −0.056, cell-level CI [−0.100, −0.008]; approximate donor-level CI [−0.678, +0.566]; Fig. 5a)", "adjudication_note": "Knowledge-graph status = supported (cell-level CI); donor-level CI spans 0. 'At all Braak stages' not tested stage-stratified.", "report_url": "/assets/reports/alzheimer-rorb-ec-vulnerability-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-rorb-ec-vulnerability-r1/OTF2", "run": "alzheimer-rorb-ec-vulnerability-r1", "disease": "AD", "hypothesis_id": "OTF2", "origin": "on_the_fly", "hypothesis": "Re-analysis restricted to GSE147528 (2,009 RORB+ cells) will have power for H1; test whether CACNA1C/D reach FDR<0.05 there.", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "CACNA1C and CACNA1D show small NEGATIVE log2FC (opposite the H1 prediction of upregulation in RORB+).", "adjudication_note": "Acted on in EXECUTE stage 8 (atlas switch); CACNA1C/D FDR=1.00.", "report_url": "/assets/reports/alzheimer-rorb-ec-vulnerability-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-rorb-ec-vulnerability-r1/OTF3", "run": "alzheimer-rorb-ec-vulnerability-r1", "disease": "AD", "hypothesis_id": "OTF3", "origin": "on_the_fly", "hypothesis": "Elevated excitability module in RORB+ neurons is driven by non-calcium genes (SCN1A, SCN8A, HCN1).", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "per-gene identification of driver genes within the module has not been performed", "adjudication_note": "Data available; not run.", "report_url": "/assets/reports/alzheimer-rorb-ec-vulnerability-r1.pdf", "report_kind": "pdf" }, { "id": "alzheimer-rorb-ec-vulnerability-r1/OTF4", "run": "alzheimer-rorb-ec-vulnerability-r1", "disease": "AD", "hypothesis_id": "OTF4", "origin": "on_the_fly", "hypothesis": "PVALB downregulation in RORB+ neurons (log2FC -1.18) reaches BH-FDR<0.05 under pydeseq2.", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "For the pseudobulk DE, use pydeseq2 (once OMP issues are resolved) which handles sparse genes more robustly than the simple t-test.", "adjudication_note": "Technical: pydeseq2 not run because of native OMP/BLAS library crashes on the analysis platform.", "report_url": "/assets/reports/alzheimer-rorb-ec-vulnerability-r1.pdf", "report_kind": "pdf" }, { "id": "ideate-parkinson-mechanism-r2/H1", "run": "ideate-parkinson-mechanism-r2", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "Lysosomal-convergence score log2(LRRK2)-log2(GBA1) identifies the most PD-depleted DA subtype in Kamath 2022 SN atlas (AUROC>=0.70, CI>0.5, beats random pair).", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "H1 is INCONCLUSIVE because the Kamath 2022 SN snRNA-seq (GSE178265, approximately 400,000 nuclei) requires dbGaP controlled-access approval", "adjudication_note": "dbGaP controlled access; only descriptive surrogate (GSE184950, 4 samples), AUROC never computed.", "report_url": "/assets/reports/ideate-parkinson-mechanism-r2.pdf", "report_kind": "pdf" }, { "id": "ideate-parkinson-mechanism-r2/H2", "run": "ideate-parkinson-mechanism-r2", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "TFEB targets (LAMP2A, CTSD, CTSB, ATP6AP1, MCOLN1) >=4/5 down with gene-set FDR<=0.10 in BOTH GBA1-N370S and LRRK2-G2019S iPSC-DA vs isogenic controls (+synergy arm).", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "The primary analysis could not be executed as pre-registered because none of the five TFEB target genes appear in the NanoString NS_HS_NEUROPATH_V1.0 panel of GSE167335", "adjudication_note": "Report/analysis label 'NOT SUPPORTED' and graph = refuted, but this rests on a post-hoc V-ATPase surrogate (8/9 up, donor-level permutation p=0.333, N=2 donors). GBA1-N370S arm blocked (no isogenic dataset); synergy arm untestable.", "report_url": "/assets/reports/ideate-parkinson-mechanism-r2.pdf", "report_kind": "pdf" }, { "id": "ideate-parkinson-mechanism-r2/H3", "run": "ideate-parkinson-mechanism-r2", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "TFEB-target composite correlates with alpha-syn protein (proteomics) in iPSC-DA (Spearman r>0.40, perm p<0.05) (+ pharmacological reversal arm).", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "H3 is BLOCKED: no matched iPSC-DA RNA-seq + lysosomal proteomics dataset with simultaneous measurement of both modalities was accessible.", "adjudication_note": "Reversal arm also untested (no treatment data).", "report_url": "/assets/reports/ideate-parkinson-mechanism-r2.pdf", "report_kind": "pdf" }, { "id": "ideate-parkinson-mechanism-r2/OTF1", "run": "ideate-parkinson-mechanism-r2", "disease": "PD", "hypothesis_id": "OTF1", "origin": "on_the_fly", "hypothesis": "LRRK2-G2019S iPSC-DA neurons show compensatory upregulation of V-ATPase subunit genes (partially reversed by MLi-2).", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "this design is fundamentally underpowered for significance testing.", "adjudication_note": "8/9 genes up, mean log2FC +0.485 (CI -0.454 to 1.471), exact donor permutation p=0.333 = minimum achievable at N=2+2. The knowledge-graph node marked supported came from the pseudo-replicated stage 3 analysis; the latest stage 8 node = inconclusive. MLi-2 reversal part never testable (no data).", "report_url": "/assets/reports/ideate-parkinson-mechanism-r2.pdf", "report_kind": "pdf" }, { "id": "ideate-parkinson-mechanism-r2/OTF2", "run": "ideate-parkinson-mechanism-r2", "disease": "PD", "hypothesis_id": "OTF2", "origin": "on_the_fly", "hypothesis": "GBA1-N370S cells (exhausted compensation) show V-ATPase DOWNregulation, distinguishing two phases of lysosomal dysfunction.", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "The GBA1 N370S arm of H2 could not be tested: no GBA1 N370S isogenic iPSC-DA RNA-seq dataset was found in accessible GEO deposits", "adjudication_note": "", "report_url": "/assets/reports/ideate-parkinson-mechanism-r2.pdf", "report_kind": "pdf" }, { "id": "ideate-parkinson-mechanism-r2/OTF3", "run": "ideate-parkinson-mechanism-r2", "disease": "PD", "hypothesis_id": "OTF3", "origin": "on_the_fly", "hypothesis": "N=2 donors/group NanoString cannot reach significance; a properly powered test needs N>=5 donors with whole-transcriptome LRRK2-G2019S iPSC-DA data.", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "N ≥ 5 independent biological replicates at the donor level is necessary", "adjudication_note": "Methodological/future-data statement; no suitable dataset fetched.", "report_url": "/assets/reports/ideate-parkinson-mechanism-r2.pdf", "report_kind": "pdf" }, { "id": "neurodeg-microglia-convergence-r1/H1", "run": "neurodeg-microglia-convergence-r1", "disease": "CROSS", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "Microglial LDAM module (LGALS3, CD9, GPNMB, NPC2) significantly elevated in EACH of AD, DLB and PDD vs NCI in GSE303823 (shared cross-dementia feature).", "verdict": "Partially supported", "outcome": "partial", "outcome_class": "positive (partial)", "evidence_quote": "Per the pre-registered decision rule, this outcome is classified as **partial sharing (DLB+PDD)**", "adjudication_note": "DLB g=1.55 & PDD g=2.64 (FDR 0.014); AD g=1.20 FDR 0.343 (n=4 vs 4, cannot reach FDR without perfect separation). Pre-specified DAM2 dissociation control failed (DAM2 co-elevated), weakening LDAM specificity. Graph per-arm nodes: DLB/PDD supported, AD inconclusive.", "report_url": "/campaign/runs/neurodeg-microglia-convergence-r1/report/", "report_kind": "html" }, { "id": "neurodeg-microglia-convergence-r1/H2", "run": "neurodeg-microglia-convergence-r1", "disease": "CROSS", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "H1 call reproduced by two orthogonal methods: (a) Leiden LDAM-like subcluster compositional shift (scCODA); (b) AUCell per-donor scores.", "verdict": "Partially supported", "outcome": "partial", "outcome_class": "positive (partial)", "evidence_quote": "The H2a result, as reported, is best understood as a threshold-sensitivity restatement of H1 rather than independent corroboration.", "adjudication_note": "OmiCairn verdict 'corroborates' (rule formally met) but H2a was a semi-circular threshold proxy (no Leiden/scCODA; 29-gene extraction) and AUCell reached FDR<0.05 for no disease, AD sign discordant. Alternative: INCONCLUSIVE.", "report_url": "/campaign/runs/neurodeg-microglia-convergence-r1/report/", "report_kind": "html" }, { "id": "neurodeg-microglia-convergence-r1/H3", "run": "neurodeg-microglia-convergence-r1", "disease": "CROSS", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "LDAM signature locked on GSE303823 transfers without refitting to held-out SEA-AD DLPFC and separates high vs low Braak donors (AUC CI lower bound >0.5).", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "Per the pre-registration, a CI spanning 0.5 constitutes a null outcome", "adjudication_note": "AUC=0.60, CI [0.45, 0.76], p=0.093, n=80 (68 high / 12 low pathology); report notes class imbalance means 'not powered evidence of absence'. Knowledge-graph status = inconclusive.", "report_url": "/campaign/runs/neurodeg-microglia-convergence-r1/report/", "report_kind": "html" }, { "id": "neurodeg-microglia-convergence-r1/H4", "run": "neurodeg-microglia-convergence-r1", "disease": "CROSS", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "LGALS3/GPNMB lipid-droplet sub-program enriched in APOE4 carriers in GSE303823 (replicating SEA-AD JT p=0.006), with SEA-AD MTG replication.", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "The APOE4-LDAM association is not replicated in this independent analysis (Fig. 4b–c).", "adjudication_note": "GSE303823 arm UNTESTABLE (no APOE metadata) -> that arm is NOT_TESTED_DATA; verdict rests on the pre-registered SEA-AD MTG arm: MWU p=0.150, r=-0.20 (opposite). Note SEA-AD MTG is the same object as the prior finding, not an independent cohort.", "report_url": "/campaign/runs/neurodeg-microglia-convergence-r1/report/", "report_kind": "html" }, { "id": "neurodeg-microglia-convergence-r1/H5", "run": "neurodeg-microglia-convergence-r1", "disease": "CROSS", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Negative control: ECM-integrin (LAMA2/COL4A2->ITGAV/ITGA6/ITGB8) disruption is AD-specific (AD g<0 FDR<0.05; DLB/PDD CIs include 0).", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "H5 verdict is **inconclusive**: neither the expected AD-specific disruption nor a shared-disruption pattern was detected.", "adjudication_note": "All contrasts near zero (FDR=1.0); no cell-type annotation, 29-gene extraction.", "report_url": "/campaign/runs/neurodeg-microglia-convergence-r1/report/", "report_kind": "html" }, { "id": "neurodeg-microglia-convergence-r1/H6", "run": "neurodeg-microglia-convergence-r1", "disease": "CROSS", "hypothesis_id": "H6", "origin": "plan", "hypothesis": "Sensitivity decomposition: H1 effect not driven by microglial proportion, survives covariates (PMI/age/sex), marker-set and resolution perturbation.", "verdict": "Partially supported", "outcome": "partial", "outcome_class": "positive (partial)", "evidence_quote": "preserved DLB elevation (g=1.87, 95% CI [1.33, 3.79]) but rendered PDD statistically ambiguous (g=0.84, 95% CI [−0.11, 2.20])", "adjudication_note": "Proportion adjustment and threshold sweep robust (DLB, PDD), but PDD attenuated with 6-gene set and PMI/age/sex covariate adjustment not feasible (absent metadata).", "report_url": "/campaign/runs/neurodeg-microglia-convergence-r1/report/", "report_kind": "html" }, { "id": "parkinson-asyn-propagation-r1/H1", "run": "parkinson-asyn-propagation-r1", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "SNCA-weighted SIR (model B) recovers Braak rank order of t_peak across 5 regions (Spearman rho>=0.70, bootstrap CI lower bound >0).", "verdict": "Supported", "outcome": "supported", "outcome_class": "positive", "evidence_quote": "Pre-registered threshold: ρ ≥ 0.70 with CI excluding 0. Both criteria met. **H1 is supported.**", "adjudication_note": "rho=1.000, degenerate CI [1,1], perm p=0.0083. Caveat: literature-fallback (murine) connectivity, connectome-only model A also rho=1.0 (ceiling). Superseded sibling run parkinson-asyn-propagation-r2 with Allen connectivity found H1 NOT SUPPORTED. This run never reached write/review.", "report_url": null, "report_kind": null }, { "id": "parkinson-asyn-propagation-r1/H2", "run": "parkinson-asyn-propagation-r1", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "Removing SNCA weighting (model A) degrades rho by >=0.30 vs model B (paired bootstrap CI excl. 0).", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "Δρ(B − A) = 0.000 (95% CI [0.000, 0.000]; p_directional = 0.998)", "adjudication_note": "Both models at ceiling.", "report_url": null, "report_kind": null }, { "id": "parkinson-asyn-propagation-r1/H3", "run": "parkinson-asyn-propagation-r1", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Within PFC, model predicts excitatory neurons reach infection threshold first; model top-3 overlaps >=2 with LAMDA pSyn-enriched top-3.", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "Vocabulary mismatch (pSyn+ TrueID format not matching profile index barcodes) forced use of all 48,702 profile rows, biasing LAMDA top-3 toward abundant cell types", "adjudication_note": "OmiCairn: NOT SUPPORTED (overlap 0, EN ranked 3rd). But LAMDA side is an all-spots proxy, and model PFC top-3 contains DMNX_Neu/GPI_Neu (annotation artefact, judged uninterpretable in sibling run parkinson-asyn-propagation-r2). Strict reading: NOT_SUPPORTED.", "report_url": null, "report_kind": null }, { "id": "parkinson-asyn-propagation-r1/H4", "run": "parkinson-asyn-propagation-r1", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "Ablating DMNX->GPi edge shifts predicted rank of at least one region by >1 position.", "verdict": "Supported", "outcome": "supported", "outcome_class": "positive", "evidence_quote": "Maximum rank shift = 3 > pre-registered threshold of > 1.", "adjudication_note": "Deterministic model result under literature-fallback connectivity; reversed (0 shift) in sibling run parkinson-asyn-propagation-r2 with Allen connectivity.", "report_url": null, "report_kind": null }, { "id": "parkinson-asyn-propagation-r1/H5", "run": "parkinson-asyn-propagation-r1", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Model-family comparison: rank connectome-only (A), SNCA-weighted (B, primary), cell-autonomous (C) by Braak rho.", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "Models A and B tie at ρ = 1.000; Model C achieves ρ = 0.400.", "adjudication_note": "Descriptive; A=B at ceiling, B-C Delta 0.601 CI [0, 2] p=0.336.", "report_url": null, "report_kind": null }, { "id": "parkinson-asyn-propagation-r2/H1", "run": "parkinson-asyn-propagation-r2", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "SNCA-weighted SIR (model B) recovers proxy Braak rank order [1,3,5,5,6] of t_peak across 5 regions (rho>=0.7, bootstrap CI lower bound >0).", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "not meeting the pre-registered criterion that requires CI exclusion of zero", "adjudication_note": "Latest EXECUTE stage 19: rho=0.711 (meets point threshold), CI [-0.304, 1.000], perm p=0.094; n=5 regions, plan conceded ~50-65% power -> borderline INCONCLUSIVE.", "report_url": "/assets/reports/parkinson-asyn-propagation-r2.pdf", "report_kind": "pdf" }, { "id": "parkinson-asyn-propagation-r2/H2", "run": "parkinson-asyn-propagation-r2", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "Removing SNCA weighting (model A, connectome-only) degrades rho by >=0.3 relative to model B.", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "the observed Δρ is negative and the CI does not exclude zero. H2 is NOT SUPPORTED.", "adjudication_note": "Delta rho(B-A) = -0.207 (CI -1.304 to 0.913); connectome-only A outperforms B (0.918; 1.000 when independently optimised, post hoc).", "report_url": "/assets/reports/parkinson-asyn-propagation-r2.pdf", "report_kind": "pdf" }, { "id": "parkinson-asyn-propagation-r2/H3", "run": "parkinson-asyn-propagation-r2", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Within PFC (cingulate proxy) excitatory L5/6 neurons reach infection threshold first; model top-3 overlaps >=2 with LAMDA Lewy-burdened top-3 (Fisher p<0.05).", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "H3 is not biologically interpretable; the following analysis is reported for pre-registration completeness only.", "adjudication_note": "OmiCairn headline 'H3 is NOT SUPPORTED' (overlap 0, Fisher p=1.0), but report itself deems it uninterpretable (DMNX_Neu/GPI_Neu annotation artefacts in PFC; sub-SIR never reached threshold).", "report_url": "/assets/reports/parkinson-asyn-propagation-r2.pdf", "report_kind": "pdf" }, { "id": "parkinson-asyn-propagation-r2/H4", "run": "parkinson-asyn-propagation-r2", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "Ablating DMNX->GPi edge shifts peak-time rank by >1 position for >=1 region.", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "Zero rank displacement (max |Δrank| = 0) was observed across all five regions after removing the DMNX→GPi edge (Fig. 5a).", "adjudication_note": "", "report_url": "/assets/reports/parkinson-asyn-propagation-r2.pdf", "report_kind": "pdf" }, { "id": "parkinson-asyn-propagation-r2/H5", "run": "parkinson-asyn-propagation-r2", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Model-family comparison: connectome-only (A), SNCA-weighted (B, primary), cell-autonomous (C) ranked by Braak rho; A or C beating B reported as-is.", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "The three model variants ranked as: Model A (ρ = 0.918, CI [0.745, 1.000]) > Model B (ρ = 0.711, CI [−0.304, 1.000]) > Model C (ρ undefined; Fig. 5b,c,d).", "adjudication_note": "UNCERTAIN mapping: H5 is descriptive ('always reportable'); verdict reflects that the primary model B did not rank best (inversion). Pairwise Delta CIs include 0; alternative INCONCLUSIVE.", "report_url": "/assets/reports/parkinson-asyn-propagation-r2.pdf", "report_kind": "pdf" }, { "id": "parkinson-cellchat-immune-axis-r1/H1", "run": "parkinson-cellchat-immune-axis-r1", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": ">=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.", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "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.", "report_url": null, "report_kind": null }, { "id": "parkinson-cellchat-immune-axis-r1/H2", "run": "parkinson-cellchat-immune-axis-r1", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "Shared L-R pairs enriched for Hong 2025 28 MR-implicated immune genes (BH q<0.05, hypergeometric).", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "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.", "report_url": null, "report_kind": null }, { "id": "parkinson-cellchat-immune-axis-r1/H3", "run": "parkinson-cellchat-immune-axis-r1", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Per-donor peripheral CD8+T MR-gene score rank-correlates with brain T-cell module score (Spearman rho>0.3, p<0.05).", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "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).", "report_url": null, "report_kind": null }, { "id": "parkinson-cellchat-immune-axis-r1/H4", "run": "parkinson-cellchat-immune-axis-r1", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "Direction-specificity control: reverse-direction inference yields fewer shared pairs and permutation p>=0.05.", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "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.", "report_url": null, "report_kind": null }, { "id": "parkinson-cellchat-immune-axis-r1/H5", "run": "parkinson-cellchat-immune-axis-r1", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Method-consensus robustness: LIANA consensus shared-pair count within +/-2 of CellPhoneDB, NATMI, scTalk counts.", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "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.", "report_url": null, "report_kind": null }, { "id": "parkinson-cellchat-immune-axis-r3/H1", "run": "parkinson-cellchat-immune-axis-r3", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": ">=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", "verdict": "Supported", "outcome": "supported", "outcome_class": "positive", "evidence_quote": "**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.", "report_url": "/assets/reports/parkinson-cellchat-immune-axis-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-cellchat-immune-axis-r3/H2", "run": "parkinson-cellchat-immune-axis-r3", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "Ligands/receptors of shared pairs enriched (q<0.05) among 28 Hong 2025 MR-implicated immune genes", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "**Decision: H2 NOT SUPPORTED (p = 0.346).**", "adjudication_note": "Only 18 genes; run notes low power (OR=2.56, CI 0.058-18.0).", "report_url": "/assets/reports/parkinson-cellchat-immune-axis-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-cellchat-immune-axis-r3/H3", "run": "parkinson-cellchat-immune-axis-r3", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Per-donor peripheral signature scores correlate with brain T-cell module scores (peripheral-foreshadow)", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "**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.", "report_url": "/assets/reports/parkinson-cellchat-immune-axis-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-cellchat-immune-axis-r3/H4", "run": "parkinson-cellchat-immune-axis-r3", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "Reverse direction (monocyte->CD8+T, microglia->CD8+T) does NOT reach H1 threshold (<5 pairs, perm p>=0.05): direction-specificity", "verdict": "Supported", "outcome": "supported", "outcome_class": "positive", "evidence_quote": "\"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.", "report_url": "/assets/reports/parkinson-cellchat-immune-axis-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-cellchat-immune-axis-r3/H5", "run": "parkinson-cellchat-immune-axis-r3", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Per-method shared-pair counts (CellPhoneDB, NATMI, scTalk, CellChat, Connectome) within +/-2 of LIANA consensus", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "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.", "report_url": "/assets/reports/parkinson-cellchat-immune-axis-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-celloracle-ko-r1/H1", "run": "parkinson-celloracle-ko-r1", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "Mean cosine between in-silico KO shift (10 GWAS genes) and PD-minus-control DA shift >0.30 with permutation p<0.01", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "**H1 verdict: NOT SUPPORTED at the pre-registered threshold** (threshold = cosine > 0.30). The mean cosine of 0.025 does not reach 0.30.", "adjudication_note": "Permutation component met (p=0.001 vs null mean -0.135) but cosine CI [-0.067,0.114] includes 0; residualized delta p=0.43. CellOracle not run (velocyto build failure) - expression-stratification proxy; DMNX_Neu fallback instead of SNpc. Could arguably be PARTIALLY_SUPPORTED (one of two rule components met).", "report_url": "/assets/reports/parkinson-celloracle-ko-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-celloracle-ko-r1/H2", "run": "parkinson-celloracle-ko-r1", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "Per-gene KO alignment correlates with fine-mapping PIP (Spearman rho>0.4, p<0.05; n=10)", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "**H2 NOT SUPPORTED** (ρ threshold = 0.4, p threshold < 0.05).", "adjudication_note": "rho=0.042; pre-flagged ~30% power.", "report_url": "/assets/reports/parkinson-celloracle-ko-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-celloracle-ko-r1/H3", "run": "parkinson-celloracle-ko-r1", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "LRRK2-KO top-100 predicted targets enriched for Hemedan 2024 prodromal module (BH q<0.05)", "verdict": "Supported", "outcome": "supported", "outcome_class": "positive", "evidence_quote": "**H3 SUPPORTED** (q < 0.05). LRRK2-KO predicted targets are significantly enriched in the Hemedan 2024 Boolean-PD prodromal regulatory module (FDR q = 0.007, FE = 4.7×).", "adjudication_note": "Overlap is 5 genes (SNCA, LRRK2, GAK, CTSB, SCARB2) in an 11-gene HVG-restricted module; overlapping genes are themselves GWAS/KO genes (possible circularity). Proxy KO method, not CellOracle.", "report_url": "/assets/reports/parkinson-celloracle-ko-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-celloracle-ko-r1/H4a", "run": "parkinson-celloracle-ko-r1", "disease": "PD", "hypothesis_id": "H4a", "origin": "plan", "hypothesis": "SNCA-KO predicts protective shift: cosine with PD-vs-ctrl vector >0, permutation p<0.05", "verdict": "Supported", "outcome": "supported", "outcome_class": "positive", "evidence_quote": "- **SNCA-KO**: cosine = +0.235, permutation p = 0.001 (one-tailed: cosine ≥ 0.235 in null). **H4a SUPPORTED**", "adjudication_note": "Literal rule met. Interpretive incoherence: positive cosine means KO shifts TOWARD the PD state, yet text calls it 'protective'.", "report_url": "/assets/reports/parkinson-celloracle-ko-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-celloracle-ko-r1/H4b", "run": "parkinson-celloracle-ko-r1", "disease": "PD", "hypothesis_id": "H4b", "origin": "plan", "hypothesis": "HBB-KO negative control predicts null shift (|cosine|<0.1)", "verdict": "Supported", "outcome": "supported", "outcome_class": "positive", "evidence_quote": "- **HBB-KO**: |cosine| = 0.032 < 0.1 threshold. **H4b SUPPORTED**", "adjudication_note": "Report notes residualized HBB cosine rises to 0.236; raw (primary) value used.", "report_url": "/assets/reports/parkinson-celloracle-ko-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-celloracle-ko-r1/H5", "run": "parkinson-celloracle-ko-r1", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "H1 mean cosine changes <=0.1 between Adams-derived ATAC base-GRN and Zenodo midbrain reference base-GRN", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "The Zenodo midbrain reference base-GRN comparison was not executed (CellOracle package unavailable due to velocyto build failure; Zenodo download was not attempted).", "adjudication_note": "Surrogate raw-vs-residualized comparison gave |delta|=0.118 (>0.1); report reports H5 'not formally supported' on the surrogate.", "report_url": "/assets/reports/parkinson-celloracle-ko-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-da-vulnerability-r4/H1", "run": "parkinson-da-vulnerability-r4", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "AGTR1+ DA fraction depleted in PD (log2FC in [-2.6,-0.95], BH-FDR<0.05) in all 3 replication atlases (Wang, Adams, Fullard SNpc)", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "adams_2024,0.9761754643911956,-0.9433853104864593,2.6413861241359333,0.8454192090937935,1.0,3,10,91,2703,False,False,-1.6", "adjudication_note": "Formal rule failed (0/2 atlases pass; Adams log2FC +0.98, Wang 0.0, FDR=1.0) but only 3 PD vs 10 ctrl (Adams, young+aged ctrl pooled) and 5 vs 4 (Wang) donors vs planned 14/8 and 23/9; Fullard never fetched. Severely underpowered; no analysis summary written. Strict reading would be NOT_SUPPORTED.", "report_url": null, "report_kind": null }, { "id": "parkinson-da-vulnerability-r4/H2", "run": "parkinson-da-vulnerability-r4", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "TP53 and NR2F2 modules upregulated in residual AGTR1+ DA cells (BH-FDR<0.05) in >=2/3 atlases", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "adams_2024,tp53,-0.887683905934536,,,0.1393939393939394,0.1393939393939394,False,194", "adjudication_note": "Only Adams evaluable (Wang/Fullard no values); >=2-atlas rule cannot be satisfied; underpowered.", "report_url": null, "report_kind": null }, { "id": "parkinson-da-vulnerability-r4/H3", "run": "parkinson-da-vulnerability-r4", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Locked consensus AGTR1+ panel stratifies PD vs ctrl in blind Martirosyan 2024 (AUC>=0.75, CI lower >0.5)", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "ERROR loading Martirosyan count table: could not convert string to float: 'MIR1302-2HG'", "adjudication_note": "Data were downloaded; failure was a parsing bug (results record labels it fetch_failed).", "report_url": null, "report_kind": null }, { "id": "parkinson-da-vulnerability-r4/H4", "run": "parkinson-da-vulnerability-r4", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "H1 depletion sign and FDR pass stable across >=4/6 Leiden resolutions in each atlas where H1 holds", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "\"atlases_stable_ge4_resolutions\": 0", "adjudication_note": "Conditional on H1 holding, which it did not; Adams FDR fails at all resolutions (and resolution-scan log2FC ~-0.55 disagrees in sign with primary +0.98); AGTR1+ not found in Wang at any resolution.", "report_url": null, "report_kind": null }, { "id": "parkinson-da-vulnerability-r4/H5", "run": "parkinson-da-vulnerability-r4", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Per-donor decomposition: AGTR1+ within-DA fraction (layer c) dominates signal reduction vs total nuclei / DA fraction", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "adams_2024,0.09759000729485331,0.7511151158040675,0.04879500364742666,0.8742219227185322,0.26911285945377744,0.373950482581387,0.34203517720054455,0.2526683107916884", "adjudication_note": "Descriptive; no layer significant in either atlas (all p>0.25); no dominance statement was written.", "report_url": null, "report_kind": null }, { "id": "parkinson-da-vulnerability-r5/H1", "run": "parkinson-da-vulnerability-r5", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "Kamath AGTR1+ DA subtype recovers and is depleted in PD (log2FC in [-2.6,-0.95], BH-FDR<0.05) in Wang, Adams and Fullard SNpc", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "The AGTR1+ cluster was not recoverable in either atlas (replication rate 0.0/2, 95% Wilson CI [0.0%, 65.8%], permutation p=1.0)", "adjudication_note": "Formal rule failed (report frames as 'pre-registered null') but attributes failure to DA yield: 52 and 27 DA cells, Adams 2 PD donors, Fullard SNpc absent. Strict reading would be NOT_SUPPORTED.", "report_url": "/assets/reports/parkinson-da-vulnerability-r5.pdf", "report_kind": "pdf" }, { "id": "parkinson-da-vulnerability-r5/H2", "run": "parkinson-da-vulnerability-r5", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "TP53 and NR2F2 stress modules upregulated in residual AGTR1+ DA cells (BH-FDR<0.05) in >=2/3 atlases", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "H2 cannot be formally evaluated because no AGTR1+ subcluster was recovered in either atlas (Fig. 4).", "adjudication_note": "Only a TP53 proxy on all DA cells (FDR 0.190); NR2F2 gene set not cached. Report labels H2 'inconclusive'.", "report_url": "/assets/reports/parkinson-da-vulnerability-r5.pdf", "report_kind": "pdf" }, { "id": "parkinson-da-vulnerability-r5/H3", "run": "parkinson-da-vulnerability-r5", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Locked consensus AGTR1+ panel classifies Martirosyan 2024 PD vs ctrl donors with AUC>=0.75, CI lower >0.5", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "The ROC AUC was 0.419 (95% bootstrap CI 0.217–0.644; Wilcoxon p=0.471; Fig. 5), falling below the pre-registered threshold of 0.75", "adjudication_note": "Panel derived from atlases with only 27-52 DA cells.", "report_url": "/assets/reports/parkinson-da-vulnerability-r5.pdf", "report_kind": "pdf" }, { "id": "parkinson-da-vulnerability-r5/H4", "run": "parkinson-da-vulnerability-r5", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "H1 sign and FDR stable across >=4/6 Leiden resolutions within each atlas that passed H1", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "(0 stable resolutions in both atlases; Fig. 2)", "adjudication_note": "Conditional on H1 passing; no atlas passed, so robustness of a non-existent effect is undefined.", "report_url": "/assets/reports/parkinson-da-vulnerability-r5.pdf", "report_kind": "pdf" }, { "id": "parkinson-da-vulnerability-r5/H5", "run": "parkinson-da-vulnerability-r5", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Decomposition of DA loss: AGTR1+-within-DA fraction (component c) is the dominant driver vs total nuclei/DA fraction", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "the dominant component of PD-vs-control DA-related change was component b — the DA-cluster fraction within total nuclei — with log2FC=−1.325 (95% CI −3.313 to −0.605)", "adjudication_note": "Descriptive; component b dominant in both atlases, component c CI spans zero; very low cell counts.", "report_url": "/assets/reports/parkinson-da-vulnerability-r5.pdf", "report_kind": "pdf" }, { "id": "parkinson-foundation-embedding-r1/H1", "run": "parkinson-foundation-embedding-r1", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "Donor-level LOO AUC: best FM (Geneformer/scGPT) beats log-CPM-PCA-LR by dAUC>=0.05 (CI>0, DeLong p<0.05) with AUC>0.75 (Wang 2024)", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "", "adjudication_note": "Run halted mid-execute (no active process; likely superseded by a relaunch) (Geneformer embedding still running); successive EXECUTE stages results/ directories empty; no results record. Hypotheses taken from latest plan the PLAN-stage hypothesis list.", "report_url": null, "report_kind": null }, { "id": "parkinson-foundation-embedding-r1/H2", "run": "parkinson-foundation-embedding-r1", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "Leiden on Geneformer embeddings recovers an AGTR1-high cluster (>=1.5x, silhouette>=0.10) in Wang PD donors", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "", "adjudication_note": "Run halted mid-execute (no active process; likely superseded by a relaunch) (Geneformer embedding still running); successive EXECUTE stages results/ directories empty; no results record.", "report_url": null, "report_kind": null }, { "id": "parkinson-foundation-embedding-r1/H3", "run": "parkinson-foundation-embedding-r1", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Geneformer fine-tuned 1 epoch achieves held-out AUC>=0.7 on Adams; random-init transformer <=0.6", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "", "adjudication_note": "Run halted mid-execute (no active process; likely superseded by a relaunch) (Geneformer embedding still running); successive EXECUTE stages results/ directories empty; no results record.", "report_url": null, "report_kind": null }, { "id": "parkinson-foundation-embedding-r1/H4", "run": "parkinson-foundation-embedding-r1", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "dAUC stable within +/-0.05 across 5K/25K/50K nuclei-per-donor subsamples", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "", "adjudication_note": "Run halted mid-execute (no active process; likely superseded by a relaunch) (Geneformer embedding still running); successive EXECUTE stages results/ directories empty; no results record.", "report_url": null, "report_kind": null }, { "id": "parkinson-foundation-embedding-r1/H5", "run": "parkinson-foundation-embedding-r1", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Wang-fitted FM donor embeddings achieve zero-shot AUC>=0.65 (CI lower>=0.50) on Adams", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "", "adjudication_note": "Run halted mid-execute (no active process; likely superseded by a relaunch) (Geneformer embedding still running); successive EXECUTE stages results/ directories empty; no results record.", "report_url": null, "report_kind": null }, { "id": "parkinson-foundation-embedding-r4/H1", "run": "parkinson-foundation-embedding-r4", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "Geneformer-V2 or scGPT donor-level LOO AUC>0.75 AND dAUC>=0.05 over log-CPM-PCA-LR with DeLong p<0.05 (Fullard multi-region)", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "**H1 decision: NOT SUPPORTED.**", "adjudication_note": "GF AUC 0.775 vs baseline 0.749; dAUC +0.026 (CI -0.066 to +0.118, p=0.290). scGPT never run (package/weights missing, HF 401). Report itself notes ~19% power and 'more precisely described as inconclusive'.", "report_url": "/campaign/runs/parkinson-foundation-embedding-r4/report/", "report_kind": "html" }, { "id": "parkinson-foundation-embedding-r4/H2", "run": "parkinson-foundation-embedding-r4", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "AGTR1+ subcluster recovery in FM embeddings", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "Inapplicable: no dopaminergic neurons in the Fullard atlas.", "adjudication_note": "Declared inapplicable already at plan stage.", "report_url": "/campaign/runs/parkinson-foundation-embedding-r4/report/", "report_kind": "html" }, { "id": "parkinson-foundation-embedding-r4/H3", "run": "parkinson-foundation-embedding-r4", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Geneformer fine-tuned on Kamath SNpc generalises to Wang and Adams (AUC>=0.70) and beats from-scratch by >=0.10", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "Deferred: GSE178265 (Kamath) count matrix absent. H3 inapplicable in this iteration.", "adjudication_note": "", "report_url": "/campaign/runs/parkinson-foundation-embedding-r4/report/", "report_kind": "html" }, { "id": "parkinson-foundation-embedding-r4/H4", "run": "parkinson-foundation-embedding-r4", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "dAUC stable within +/-0.05 across 5K/25K/50K nuclei-per-donor subsamples", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "Pre-registered subsampling levels (5K/25K/50K cells/donor) were not feasible on CPU/MPS hardware. Evaluated at 25/50/100 cells/donor", "adjudication_note": "Compute-limited proxy at 25/50/100 cells (50-500x below plan); run/report declare H4 'STABLE' (range 0.044) on the proxy levels, all dAUC CIs span 0. Could be read as SUPPORTED-on-proxy.", "report_url": "/campaign/runs/parkinson-foundation-embedding-r4/report/", "report_kind": "html" }, { "id": "parkinson-foundation-embedding-r4/H5", "run": "parkinson-foundation-embedding-r4", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Fullard-trained FM embeddings zero-shot AUC>=0.65 with CI lower>=0.50 on BOTH Wang and Adams", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "| Geneformer (zero-shot) | 0.694 | [0.324, 1.000] | **MET** |", "adjudication_note": "DISCREPANCY: run/report say threshold MET, but pre-registered rule also requires CI lower bound >=0.50 (0.324 fails) on both atlases; Wang arm deferred (tar extraction pending); n=13 Adams. Baseline zero-shot AUC 0.944 exceeds GF. Strict reading would be NOT_SUPPORTED.", "report_url": "/campaign/runs/parkinson-foundation-embedding-r4/report/", "report_kind": "html" }, { "id": "parkinson-gut-brain-axis-r2/H1", "run": "parkinson-gut-brain-axis-r2", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": ">=15 KEGG modules shared between Wallen 2022 top-100 PD-enriched MetaCyc pathways and Fullard DMNX top-100 enriched modules, hypergeometric p<0.01", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "H1: k=3, hypergeometric_p=0.3533, permutation_p=0.361, expected=2.11", "adjudication_note": "Module universe only 131, Fullard side mapped to 6 modules.", "report_url": null, "report_kind": null }, { "id": "parkinson-gut-brain-axis-r2/H2", "run": "parkinson-gut-brain-axis-r2", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "7-gene vagal-afferent module DE in DMNX (FDR<0.05) AND anti-correlated with SCFA-producer depletion (rho<-0.3, perm p<0.05)", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "\"module_de_fdr\": 0.995650997579099,", "adjudication_note": "Correlation arm implemented as module-vs-disease-label Spearman, not vs SCFA abundance.", "report_url": null, "report_kind": null }, { "id": "parkinson-gut-brain-axis-r2/H3", "run": "parkinson-gut-brain-axis-r2", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "DMNX microglia upregulate TLR4/TLR2/CD14/NLRP3 module (FDR<0.05) AND correlate with Wallen LPS-producer abundance AND DMNX effect > SNpc, V1", "verdict": "Partially supported", "outcome": "partial", "outcome_class": "positive (partial)", "evidence_quote": "\"note\": \"SNpc/V1 microglia not streamed in this run to conserve memory; DMNX only\"", "adjudication_note": "Pipeline output 'SUPPORTED' (module FDR 0.011, z-corr perm p 0.012), but the 'cross-modality' correlation was computed between module score and disease label (code never uses LPS-producer signature) and spatial-specificity arm not run. Only DE component genuinely met. Re-run 093856 found FDR 0.514.", "report_url": null, "report_kind": null }, { "id": "parkinson-gut-brain-axis-r2/H4", "run": "parkinson-gut-brain-axis-r2", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "Storm 2025 MR-causal PD proteins (fallback: Hallqvist 2024 panel) over-represented in Wallen PD-enriched bacterial pathways (perm p<0.05)", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "H4: observed=0, expected=2.82, p=1", "adjudication_note": "Pre-registered Hallqvist 8-protein surrogate used.", "report_url": null, "report_kind": null }, { "id": "parkinson-gut-brain-axis-r2/H5", "run": "parkinson-gut-brain-axis-r2", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Negative-control modules (catecholamine, ferroptosis, cuproptosis) do NOT show H1-level alignment (<15 modules, p>=0.01)", "verdict": "Supported", "outcome": "supported", "outcome_class": "positive", "evidence_quote": "\"h5_verdict\": \"all_below_threshold\"", "adjudication_note": "Specificity control holds but is moot since H1 itself failed.", "report_url": null, "report_kind": null }, { "id": "parkinson-gut-brain-axis-r4/H1", "run": "parkinson-gut-brain-axis-r4", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": ">=15 bridging KEGG modules shared between Wallen 2022 top-100 MetaCyc pathways and Fullard DMNX top-100 enriched modules (131-module catalogue), hypergeometric p<0.01", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "Observed shared KEGG module count between K_w (33 Wallen-derived modules) and K_f (30 Fullard-derived modules) = 10, below the pre-registered threshold of 15.", "adjudication_note": "Hypergeometric p=0.175.", "report_url": "/assets/reports/parkinson-gut-brain-axis-r4.pdf", "report_kind": "pdf" }, { "id": "parkinson-gut-brain-axis-r4/H2", "run": "parkinson-gut-brain-axis-r4", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "7-gene vagal-afferent module DE in DMNX pseudobulk (FDR<0.05) AND anti-correlated with Wallen SCFA-producer abundance (rho<-0.3, perm p<0.05)", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "**H2 NOT SUPPORTED.** BH-FDR = 0.463 > 0.05.", "adjudication_note": "", "report_url": "/assets/reports/parkinson-gut-brain-axis-r4.pdf", "report_kind": "pdf" }, { "id": "parkinson-gut-brain-axis-r4/H3", "run": "parkinson-gut-brain-axis-r4", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "DMNX Micro_PVM TLR/LPS-response module up in PD (FDR<0.05) AND correlates with Wallen LPS-producer abundance", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "**H3 NOT SUPPORTED.** BH-FDR = 0.514 > 0.05.", "adjudication_note": "Cross-cohort correlation arm could not be formally tested (no shared donors).", "report_url": "/assets/reports/parkinson-gut-brain-axis-r4.pdf", "report_kind": "pdf" }, { "id": "parkinson-gut-brain-axis-r4/H4", "run": "parkinson-gut-brain-axis-r4", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "Hallqvist 2024 plasma proteins (pre-registered fallback for Storm 2025 MR) over-represented in Wallen PD-enriched pathway modules (perm p<0.05)", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "**H4 NOT SUPPORTED.** Permutation p = 0.373 > 0.05.", "adjudication_note": "", "report_url": "/assets/reports/parkinson-gut-brain-axis-r4.pdf", "report_kind": "pdf" }, { "id": "parkinson-gut-brain-axis-r4/H5", "run": "parkinson-gut-brain-axis-r4", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Negative-control modules (catecholamine, ferroptosis, cuproptosis) show no significant alignment (all hypergeometric p>=0.05)", "verdict": "Supported", "outcome": "supported", "outcome_class": "positive", "evidence_quote": "**H5 PASSED (all controls null).**", "adjudication_note": "All p=1.0; specificity control moot given H1 null.", "report_url": "/assets/reports/parkinson-gut-brain-axis-r4.pdf", "report_kind": "pdf" }, { "id": "parkinson-lamda-multiregion-r2/H1", "run": "parkinson-lamda-multiregion-r2", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": ">=3 non-cortical (region x cell-type) combos show positive LAMDA enrichment in PD (BH-FDR<0.05, d>0.25) in Fullard atlas", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "", "adjudication_note": "Run halted mid-execute (no active process; likely superseded by a relaunch) while loading DMNX expression; EXECUTE-stage results empty, no results record.", "report_url": null, "report_kind": null }, { "id": "parkinson-lamda-multiregion-r2/H2", "run": "parkinson-lamda-multiregion-r2", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "LAMDA module score in PD follows Braak ordering DMNX>=SNpc>=GPi>=M1>=V1 (Spearman rho>0, perm p<0.05)", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "", "adjudication_note": "Run halted mid-execute (no active process; likely superseded by a relaunch) while loading DMNX expression; EXECUTE-stage results empty, no results record.", "report_url": null, "report_kind": null }, { "id": "parkinson-lamda-multiregion-r2/H3", "run": "parkinson-lamda-multiregion-r2", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "LAMDA higher in excitatory/projection neurons than inhibitory in >=2/5 regions (BH p<0.05, r>0.10)", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "", "adjudication_note": "Run halted mid-execute (no active process; likely superseded by a relaunch) while loading DMNX expression; EXECUTE-stage results empty, no results record.", "report_url": null, "report_kind": null }, { "id": "parkinson-lamda-multiregion-r2/H4", "run": "parkinson-lamda-multiregion-r2", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "LAMDA sub-program co-activation higher in cortex than subcortex (perm p<0.05)", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "", "adjudication_note": "Run halted mid-execute (no active process; likely superseded by a relaunch) while loading DMNX expression; EXECUTE-stage results empty, no results record.", "report_url": null, "report_kind": null }, { "id": "parkinson-lamda-multiregion-r2/H5", "run": "parkinson-lamda-multiregion-r2", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Orbitofrontal positive control: LAMDA higher in PD/PDD/DLB vs ctrl in Goralski CosMx (p<0.001)", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "", "adjudication_note": "Run halted mid-execute (no active process; likely superseded by a relaunch) while loading DMNX expression; EXECUTE-stage results empty, no results record.", "report_url": null, "report_kind": null }, { "id": "parkinson-lamda-multiregion-r3/H1", "run": "parkinson-lamda-multiregion-r3", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "LAMDA module generalises to non-cortical regions: >=3 non-cortical region x cell-type pairs with PD>ctrl at FDR<0.05 and Cohen's d>0.25 (Fullard atlas).", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "All effect sizes negative (PD < control). Primary count: 0/22 noncortical pairs (threshold >= 3).", "adjudication_note": "", "report_url": "/assets/reports/parkinson-lamda-multiregion-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-lamda-multiregion-r3/H2", "run": "parkinson-lamda-multiregion-r3", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "LAMDA enrichment in PD follows a Braak-stage regional gradient (region-ordered Spearman, permutation p<0.05).", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "Region-ordered Spearman rho = 0.500, one-sided permutation p = 0.825.", "adjudication_note": "", "report_url": "/assets/reports/parkinson-lamda-multiregion-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-lamda-multiregion-r3/H3", "run": "parkinson-lamda-multiregion-r3", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "LAMDA higher in EN vs IN in >=2/3 cortical regions AND in >=1 subcortical projection-neuron type (DMNX_Neu/GPI_Neu) vs background.", "verdict": "Partially supported", "outcome": "partial", "outcome_class": "positive (partial)", "evidence_quote": "**Result: CORTEX SUPPORTED; SUBCORTEX NOT SUPPORTED**", "adjudication_note": "Cortical arm met (d=0.87-1.12); subcortical arm (DMNX FDR=0.216, GPi FDR=0.811) failed, so the AND rule is not fully met. Report notes EN>IN tested in PD donors only and may hold in controls too (not disease-specific).", "report_url": "/assets/reports/parkinson-lamda-multiregion-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-lamda-multiregion-r3/H4", "run": "parkinson-lamda-multiregion-r3", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "LAMDA sub-programs (synaptic, mito, proteostasis, vesicle, immune) show cortical vs subcortical dissociation.", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "Max cortical vs subcortical Cohen's d difference: 0.171 (below 0.20 threshold).", "adjudication_note": "Executed test (correlation d-difference >0.20) deviates from the pre-registered LME 3-way interaction at FDR<0.05; results record lists sub-program genes with in_lamda_200=0.", "report_url": "/assets/reports/parkinson-lamda-multiregion-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-lamda-multiregion-r3/H5", "run": "parkinson-lamda-multiregion-r3", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Positive control: LAMDA higher in pSyn+ vs pSyn- CosMx cells of held-out Goralski orbitofrontal data (Wilcoxon p<0.001).", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "Orbitofrontal CosMx count matrix not present in Zenodo 10729767 deposit.", "adjudication_note": "", "report_url": "/assets/reports/parkinson-lamda-multiregion-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-lincs-reversal-r1/H1", "run": "parkinson-lincs-reversal-r1", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "Top-50 LINCS L1000 reversers of DMNX_Neu PD signature include >=5 compounds with prior PD-repositioning evidence (hypergeometric q<0.01).", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "contract: missing: results record, analysis summary, figure legends, analysis code, summary, completion flag", "adjudication_note": "Run halted: successive EXECUTE stages produced no results (stage 4 log ends in a connection error); run later closed as halted and superseded by parkinson-lincs-reversal-r4. Hypotheses from PLAN stage 2 (latest plan).", "report_url": null, "report_kind": null }, { "id": "parkinson-lincs-reversal-r1/H2", "run": "parkinson-lincs-reversal-r1", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": ">=2 of 5 pre-specified PD-relevant drug classes enriched in top-50 reversers (Fisher, BH q<0.05).", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "contract: missing: results record, analysis summary, figure legends, analysis code, summary, completion flag", "adjudication_note": "Run halted: successive EXECUTE stages produced no results (stage 4 log ends in a connection error); run later closed as halted and superseded by parkinson-lincs-reversal-r4. Hypotheses from PLAN stage 2 (latest plan).", "report_url": null, "report_kind": null }, { "id": "parkinson-lincs-reversal-r1/H3", "run": "parkinson-lincs-reversal-r1", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "DMNX_Neu vs Micro_PVM connectivity rankings poorly correlated (Pearson r<0.3, CI upper <0.3).", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "contract: missing: results record, analysis summary, figure legends, analysis code, summary, completion flag", "adjudication_note": "Run halted: successive EXECUTE stages produced no results (stage 4 log ends in a connection error); run later closed as halted and superseded by parkinson-lincs-reversal-r4. Hypotheses from PLAN stage 2 (latest plan).", "report_url": null, "report_kind": null }, { "id": "parkinson-lincs-reversal-r1/H4", "run": "parkinson-lincs-reversal-r1", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "Neuronal-cell-line L1000 subset top-50 has >=8 compounds with prior PD evidence, more than all-lines top-50.", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "contract: missing: results record, analysis summary, figure legends, analysis code, summary, completion flag", "adjudication_note": "Run halted: successive EXECUTE stages produced no results (stage 4 log ends in a connection error); run later closed as halted and superseded by parkinson-lincs-reversal-r4. Hypotheses from PLAN stage 2 (latest plan).", "report_url": null, "report_kind": null }, { "id": "parkinson-lincs-reversal-r1/H5", "run": "parkinson-lincs-reversal-r1", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Sanity gate: levodopa/ropinirole/pramipexole/rasagiline not in top-50 reversers.", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "contract: missing: results record, analysis summary, figure legends, analysis code, summary, completion flag", "adjudication_note": "Run halted: successive EXECUTE stages produced no results (stage 4 log ends in a connection error); run later closed as halted and superseded by parkinson-lincs-reversal-r4. Hypotheses from PLAN stage 2 (latest plan).", "report_url": null, "report_kind": null }, { "id": "parkinson-lincs-reversal-r4/H1", "run": "parkinson-lincs-reversal-r4", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": ">=5 of top-50 LINCS touchstone reversers of DMNX_Neu PD signature have prior PD repositioning evidence (hypergeometric p<0.01).", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "an uninterpretable null attributable to an underpowered evidence set (M = 33; minimum M ≈ 243 required for a testable H1)", "adjudication_note": "Formally fails the rule (k=0/50, q=1.0) and the run labels it 'NOT SUPPORTED'; but the evidence set was severely limited by CLUE API HTTP 401 (access) errors and H5 gate also failed (pre-reg: H1 not valid if H5 fails). Alternative reading: NOT_SUPPORTED.", "report_url": "/assets/reports/parkinson-lincs-reversal-r4.pdf", "report_kind": "pdf" }, { "id": "parkinson-lincs-reversal-r4/H2", "run": "parkinson-lincs-reversal-r4", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "Top-50 reversers enriched for >=2 of 5 PD-relevant drug classes (Fisher, BH q<0.05).", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "This result reflects a data-access limitation, not a biological finding, and H2 cannot be interpreted.", "adjudication_note": "Run labels 'NOT SUPPORTED', but MoA annotations were unavailable (CLUE API 401), so all classes had zero annotated members.", "report_url": "/assets/reports/parkinson-lincs-reversal-r4.pdf", "report_kind": "pdf" }, { "id": "parkinson-lincs-reversal-r4/H3", "run": "parkinson-lincs-reversal-r4", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "DMNX_Neu and Micro_PVM connectivity rankings poorly correlated (Pearson r<0.3 AND CI upper <0.3).", "verdict": "Supported", "outcome": "supported", "outcome_class": "positive", "evidence_quote": "The pre-registered threshold (r < 0.3 AND CI upper < 0.3) is satisfied: the 95% CI upper bound (0.172) is well below 0.3.", "adjudication_note": "r=0.133 [0.094,0.172]; computed on LINCS Level 2 data substituted for pre-registered Level 5 COMPZ; H5 sanity gate borderline-failed on same data.", "report_url": "/assets/reports/parkinson-lincs-reversal-r4.pdf", "report_kind": "pdf" }, { "id": "parkinson-lincs-reversal-r4/H4", "run": "parkinson-lincs-reversal-r4", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "Neuronal-cell-line subset top-50 has >=8 PD-evidence compounds and Fisher p<0.05 vs all-lines k1.", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "Neuronal-cell-line (NEU/NPC/FIBRNPC) top-50: k4 = 1; all-cell-lines top-50: k1 = 0. Fisher's exact p = 0.500", "adjudication_note": "Same M=33 evidence-set limitation as H1; could be read as INCONCLUSIVE.", "report_url": "/assets/reports/parkinson-lincs-reversal-r4.pdf", "report_kind": "pdf" }, { "id": "parkinson-lincs-reversal-r4/H5", "run": "parkinson-lincs-reversal-r4", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Sanity gate: ropinirole and pramipexole both above median connectivity (mimicking tail), not reversers.", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "**H5 Decision: FAIL (borderline).**", "adjudication_note": "Ropinirole 47.8th percentile (<50th); pramipexole 53.6th; selegiline 87.2th.", "report_url": "/assets/reports/parkinson-lincs-reversal-r4.pdf", "report_kind": "pdf" }, { "id": "parkinson-metabolic-flux-sn-r1/H1", "run": "parkinson-metabolic-flux-sn-r1", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "Composite primary: iMAT/Recon3D DA-neuron PD glycolytic flux decrease (H1a ratio<0.9, CI excl 1) AND sign concordance with Supandi 2018 (H1b).", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "With n=2 PD, no meaningful bootstrap CI can be formed.", "adjudication_note": "Composite of H1a+H1b. Run labels H1 'NOT SUPPORTED' (ratio 1.000, CI [1.000,1.000]); Run executed with a 54-reaction minimal model, ATPM objective, and only 2 PD / 4 ctrl donors passing QC; review (stage 8) flagged ATPM objective as incapable of detecting glycolytic change and requested a re-execution, which (EXECUTE stage 9) did not produce the required outputs.", "report_url": "/assets/reports/parkinson-metabolic-flux-sn-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-metabolic-flux-sn-r1/H1a", "run": "parkinson-metabolic-flux-sn-r1", "disease": "PD", "hypothesis_id": "H1a", "origin": "plan", "hypothesis": "Bootstrap median PD/ctrl glycolytic flux ratio in DA neurons <0.9 with 95% CI excluding 1.0.", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "the null primary result provides empirical evidence that minimal-model approaches with small sample sizes are insufficient for detecting cell-type-specific PD metabolic flux changes", "adjudication_note": "Observed ratio 1.000 [1.000,1.000] fails the rule literally (run: NOT SUPPORTED), but result is a model-degeneracy/n=2 artefact. Alternative reading: NOT_SUPPORTED.", "report_url": "/assets/reports/parkinson-metabolic-flux-sn-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-metabolic-flux-sn-r1/H1b", "run": "parkinson-metabolic-flux-sn-r1", "disease": "PD", "hypothesis_id": "H1b", "origin": "plan", "hypothesis": "Per-reaction flux-change signs concordant with Supandi 2018 in >=70% of shared reactions (binomial p<0.01).", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "The directional labels tested by the binomial test are thus assigned to numerical noise rather than meaningful flux changes.", "adjudication_note": "Decision rule nominally met (15/18 = 83.3%, p=0.0038; run says CONFIRMED), but all glycolysis deviations are <=1e-11 (solver precision). Alternative reading: SUPPORTED (nominal).", "report_url": "/assets/reports/parkinson-metabolic-flux-sn-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-metabolic-flux-sn-r1/H2", "run": "parkinson-metabolic-flux-sn-r1", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "Top-10 TIMBR-predicted biomarker metabolites include >=4 replicated in Shao/Luo 2024 meta-analysis (hypergeometric q<0.05).", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "The p-value for 3/8 overlap against the 531-metabolite universe is 0.0083, but n_overlap = 3 < 4 required. H2 is not supported.", "adjudication_note": "TIMBR replaced by an iMAT exchange-flux surrogate (H2_SURROGATE).", "report_url": "/assets/reports/parkinson-metabolic-flux-sn-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-metabolic-flux-sn-r1/H3", "run": "parkinson-metabolic-flux-sn-r1", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Iron-metabolism reaction flux ratio in PD DA neurons >1.1 with CI excluding 1.0.", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "the inactivity is a model-architecture consequence, not a biological finding.", "adjudication_note": "All iron reactions ratio=0.000 (zero flux under ATPM objective); run labels NOT SUPPORTED. Alternative reading: NOT_SUPPORTED.", "report_url": "/assets/reports/parkinson-metabolic-flux-sn-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-metabolic-flux-sn-r1/H4", "run": "parkinson-metabolic-flux-sn-r1", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "Per-reaction flux-change direction concordant across contextualisation methods (max pairwise Spearman rho >=0.5).", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "The high ρ is consistent with both interpretations.", "adjudication_note": "Rule nominally met (iMAT vs E-Flux rho=0.944; run says CONFIRMED) but only 2 methods (no TIMBR) and report attributes high rho to bimodal model degeneracy. Alternative reading: SUPPORTED (nominal).", "report_url": "/assets/reports/parkinson-metabolic-flux-sn-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-metabolic-flux-sn-r1/H5", "run": "parkinson-metabolic-flux-sn-r1", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Glycolysis signal cell-type separation: compare DA neurons vs Fullard GPi neurons and Micro_PVM (descriptive).", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "\"fullard_access\": \"not_attempted\",", "adjudication_note": "Fullard atlas not attempted (no data-availability reason given); replaced by same-dataset PD vs PD+PDD sensitivity surrogate (H5_SURROGATE_da_only).", "report_url": "/assets/reports/parkinson-metabolic-flux-sn-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-multimodal-ppmi-trajectory-r1/H1", "run": "parkinson-multimodal-ppmi-trajectory-r1", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "GPLVM 1-D latent disease-time from PPMI published summary tables correlates with time-from-diagnosis (rho>0.6, CI lower>0.4, n>=50).", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "**H1 is INCONCLUSIVE.** The n < 50 requirement is not met because the fetched supplements do not contain per-visit longitudinal group-mean time series", "adjudication_note": "rho=0.430 [-0.459,0.953], n=10 (FactorAnalysis fallback; GPy unavailable). Literal rule (CI lower <0.2 => not supported) would give NOT_SUPPORTED; data limitation could also justify NOT_TESTED_DATA.", "report_url": "/assets/reports/parkinson-multimodal-ppmi-trajectory-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-multimodal-ppmi-trajectory-r1/H2", "run": "parkinson-multimodal-ppmi-trajectory-r1", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "Model trained without dMRI recovers free-water dMRI rank order (leave-dMRI-out rho>=0.4, CI lower>0).", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "H2 is formally unevaluable under the pre-registration rules", "adjudication_note": "Leave-dMRI-out rho=0.349 at n=10, CIs not estimable. Could also be read as NOT_TESTED_DATA.", "report_url": "/assets/reports/parkinson-multimodal-ppmi-trajectory-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-multimodal-ppmi-trajectory-r1/H3", "run": "parkinson-multimodal-ppmi-trajectory-r1", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "LRRK2-G2019S carriers show leftward-shifted disease-time vs sporadic PD at matched stage (d>0.5, p<0.0125).", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "**H3 verdict: NOT EVALUABLE.** Only one LRRK2 group-mean row was recovered.", "adjudication_note": "", "report_url": "/assets/reports/parkinson-multimodal-ppmi-trajectory-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-multimodal-ppmi-trajectory-r1/H4", "run": "parkinson-multimodal-ppmi-trajectory-r1", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "No single modality contributes >=70% of loading on the 1-D latent (multi-modal claim).", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "**H4 verdict: VIOLATED — proteomics accounts for ~100% of the FA loading.**", "adjudication_note": "Report attributes dominance to feature-count imbalance (31 proteomics features) at n=10, not biology.", "report_url": "/assets/reports/parkinson-multimodal-ppmi-trajectory-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-multimodal-ppmi-trajectory-r1/H5", "run": "parkinson-multimodal-ppmi-trajectory-r1", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Descriptive audit of machine-readability of 6 cited PPMI supplements (>=4/6 strong, 2-3/6 partial, <=1/6 negative).", "verdict": "Partially supported", "outcome": "partial", "outcome_class": "positive (partial)", "evidence_quote": "Summary: 3 machine-readable (a), 2 PDF-table (b), 1 unreachable (c).", "adjudication_note": "Descriptive/classificatory hypothesis; 3/6 falls in pre-specified 'partial' band. Additionally 0/6 contained per-visit longitudinal group means.", "report_url": "/assets/reports/parkinson-multimodal-ppmi-trajectory-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-multimodal-spatial-proteomics-r1/H1", "run": "parkinson-multimodal-spatial-proteomics-r1", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "MOFA+ on snRNA+Visium+proteomics yields >=1 factor with >5% variance in each modality AND PD-associated (Wilcoxon p<0.05).", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "contract: missing: completion flag", "adjudication_note": "Run halted in PLAN (PLAN stage 3 did not complete; no completion flag); never reached EXECUTE. Hypotheses from the PLAN-stage hypothesis list (unfinalised plan).", "report_url": null, "report_kind": null }, { "id": "parkinson-multimodal-spatial-proteomics-r1/H2", "run": "parkinson-multimodal-spatial-proteomics-r1", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "Removing proteomics drops the matched factor's Visium explained variance by >=30 pp (permutation p<0.05).", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "contract: missing: completion flag", "adjudication_note": "Run halted in PLAN (PLAN stage 3 did not complete; no completion flag); never reached EXECUTE. Hypotheses from the PLAN-stage hypothesis list (unfinalised plan).", "report_url": null, "report_kind": null }, { "id": "parkinson-multimodal-spatial-proteomics-r1/H3", "run": "parkinson-multimodal-spatial-proteomics-r1", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Top-100 H1-factor genes enriched for LAMDA and/or Hemedan Boolean-PD regulators (hypergeometric q<0.05).", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "contract: missing: completion flag", "adjudication_note": "Run halted in PLAN (PLAN stage 3 did not complete; no completion flag); never reached EXECUTE. Hypotheses from the PLAN-stage hypothesis list (unfinalised plan).", "report_url": null, "report_kind": null }, { "id": "parkinson-multimodal-spatial-proteomics-r1/H4", "run": "parkinson-multimodal-spatial-proteomics-r1", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "No single modality contributes >60% of H1-factor explained variance.", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "contract: missing: completion flag", "adjudication_note": "Run halted in PLAN (PLAN stage 3 did not complete; no completion flag); never reached EXECUTE. Hypotheses from the PLAN-stage hypothesis list (unfinalised plan).", "report_url": null, "report_kind": null }, { "id": "parkinson-multimodal-spatial-proteomics-r1/H5", "run": "parkinson-multimodal-spatial-proteomics-r1", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "No pairwise MOFA+ model recovers a factor with loading |r|>=0.7 to the H1 factor.", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "contract: missing: completion flag", "adjudication_note": "Run halted in PLAN (PLAN stage 3 did not complete; no completion flag); never reached EXECUTE. Hypotheses from the PLAN-stage hypothesis list (unfinalised plan).", "report_url": null, "report_kind": null }, { "id": "parkinson-multimodal-spatial-proteomics-r3/H1", "run": "parkinson-multimodal-spatial-proteomics-r3", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "3-modal MOFA+ (snRNA+spatial+proteomics) yields >=1 factor with R2>5% in all three modalities AND PD-associated (Wilcoxon p<0.05).", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "Strictly, H1 should be labelled NOT EVALUABLE rather than NOT SUPPORTED", "adjudication_note": "Run labels H1 'NOT SUPPORTED'; spatial (dbGaP-protected GeoMx) and proteomics (no processed table) unavailable; only a 1-modal snRNA surrogate was run (Factor 1 Wilcoxon p=0.948).", "report_url": "/assets/reports/parkinson-multimodal-spatial-proteomics-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-multimodal-spatial-proteomics-r3/H2", "run": "parkinson-multimodal-spatial-proteomics-r3", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "Proteomics ablation drops spatial R2 of matched factor by >=30 pp.", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "Requires spatial modality per-donor count matrices (Δ R²_spatial between 3-modal and 2-modal MOFA+). No per-donor GeoMx spatial data could be obtained", "adjudication_note": "", "report_url": "/assets/reports/parkinson-multimodal-spatial-proteomics-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-multimodal-spatial-proteomics-r3/H3", "run": "parkinson-multimodal-spatial-proteomics-r3", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Top-100 H1-factor genes enriched for LAMDA ∪ Hemedan (hypergeometric q<0.05); not evaluable if H1 null not rejected.", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "If H1₀ is not rejected, H3 is \"not evaluable.\"", "adjudication_note": "Discrepancy: run/report report H3 SUPPORTED (q_BH=5.07e-9) but on a 1-modal surrogate Factor 1 that captures DA cell-type composition, not the pre-registered H1 factor; per pre-reg H3 is not evaluable. Also k/OR differ between analysis summary (k=12, OR=10.6) and report (k=13, OR=11.7). Alternative reading: SUPPORTED (proxy).", "report_url": "/assets/reports/parkinson-multimodal-spatial-proteomics-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-multimodal-spatial-proteomics-r3/H4", "run": "parkinson-multimodal-spatial-proteomics-r3", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "No single modality contributes >60% of H1-factor explained variance.", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "Requires all three modalities to compute per-modality variance fractions. With only snRNA-seq, the fraction is trivially 100% snRNA-seq.", "adjudication_note": "", "report_url": "/assets/reports/parkinson-multimodal-spatial-proteomics-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-multimodal-spatial-proteomics-r3/H5", "run": "parkinson-multimodal-spatial-proteomics-r3", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "No pairwise MOFA+ model recovers factor with |r|>=0.70 to the H1 factor.", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "Requires pairwise MOFA+ models with spatial and proteomics modalities.", "adjudication_note": "", "report_url": "/assets/reports/parkinson-multimodal-spatial-proteomics-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-plasma-prodromal-panel-r3/H1", "run": "parkinson-plasma-prodromal-panel-r3", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "Re-processing PXD046355 with DIA-NN + locked 8-protein LR yields 5-fold CV AUC >=0.85 for iRBD converter vs non-converter.", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "**H1 (primary) BLOCKED**: DIA-NN 1.9.2 is Linux-only and unavailable on [the analysis platform]; PRIDE PXD046355 API returns empty file listing", "adjudication_note": "Blocked by raw-spectra inaccessibility and missing converter labels (also a tool/platform limitation).", "report_url": "/campaign/runs/parkinson-plasma-prodromal-panel-r3/report/", "report_kind": "html" }, { "id": "parkinson-plasma-prodromal-panel-r3/H2", "run": "parkinson-plasma-prodromal-panel-r3", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "Per-protein univariate Cox HR signs match Hällqvist 2024 published HR directions (binomial).", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "Hällqvist 2024 did not report Cox regression — the analysis used SVM and OPLS-DA, so there are no published Cox HRs to compare against.", "adjudication_note": "", "report_url": "/campaign/runs/parkinson-plasma-prodromal-panel-r3/report/", "report_kind": "html" }, { "id": "parkinson-plasma-prodromal-panel-r3/H3", "run": "parkinson-plasma-prodromal-panel-r3", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Adding the 8-protein panel to clinical baseline improves 5-yr time-dependent AUC by >0.05 (CI excludes 0).", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "Both H2 and H3 are blocked pending raw data access.", "adjudication_note": "", "report_url": "/campaign/runs/parkinson-plasma-prodromal-panel-r3/report/", "report_kind": "html" }, { "id": "parkinson-plasma-prodromal-panel-r3/H4", "run": "parkinson-plasma-prodromal-panel-r3", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "HR directions of 6 overlapping panel proteins match between Hällqvist (LC-MS) and Gan 2025 UKB Olink (>=4/6).", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "- **H4 is NOT SUPPORTED** (pre-registered threshold: ≥4/6 with p < 0.05)", "adjudication_note": "3/6 concordant, p=0.656. Hällqvist side used PD-vs-HC signed p-values (Figure_03) as a proxy for conversion HRs, which were not published; alternative reading NOT_TESTED_DATA.", "report_url": "/campaign/runs/parkinson-plasma-prodromal-panel-r3/report/", "report_kind": "html" }, { "id": "parkinson-plasma-prodromal-panel-r3/H5", "run": "parkinson-plasma-prodromal-panel-r3", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Functional sub-panels (inflammation, proteostasis, lipid) tested in 5-fold CV; any sub-panel AUC>0.75 = dominant.", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "H5 requires per-sample protein intensities for the 72 iRBD samples to compute sub-panel AUCs, blocked by the same DIA-NN/PRIDE dependency as H1.", "adjudication_note": "", "report_url": "/campaign/runs/parkinson-plasma-prodromal-panel-r3/report/", "report_kind": "html" }, { "id": "parkinson-plasma-prodromal-panel-r4/H1", "run": "parkinson-plasma-prodromal-panel-r4", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "Locked 8-protein LR on PXD046355 (DIA-NN or MOESM4 fallback) achieves 5-fold CV AUC >=0.85 for iRBD converter vs non-converter.", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "**Result: NOT SUPPORTED under the pre-registered label protocol. However, a post-hoc clean-negative sensitivity analysis recovers AUC = 0.925", "adjudication_note": "Primary AUC=0.554 [0.437,0.678] fails the rule (run: NOT SUPPORTED), but labels were inferred from MonthsSinceBaseline and contaminated (40 future converters in non-converter class); confirmed labels unavailable. Alternative reading: NOT_SUPPORTED.", "report_url": "/assets/reports/parkinson-plasma-prodromal-panel-r4.pdf", "report_kind": "pdf" }, { "id": "parkinson-plasma-prodromal-panel-r4/H2", "run": "parkinson-plasma-prodromal-panel-r4", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "Univariate Cox HR signs of 8 panel proteins match Hällqvist Supp Table 3 conversion HR signs (>=6/8 with binomial p<0.05).", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "**Result: 6/8 concordant (75%) — SURROGATE ANALYSIS, not primary H2.**", "adjudication_note": "Reference Cox HRs not published; SVM coefficients used as surrogate (6/8, p=0.145, which would fail even loose acceptance). Pre-reg declared H2 'blocked' in this case. Alternative reading: NOT_SUPPORTED.", "report_url": "/assets/reports/parkinson-plasma-prodromal-panel-r4.pdf", "report_kind": "pdf" }, { "id": "parkinson-plasma-prodromal-panel-r4/H3", "run": "parkinson-plasma-prodromal-panel-r4", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Panel adds ΔAUC>0.05 over clinical-only (age, sex, MoCA, UPSIT) Cox model, CI lower >0.", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "The SDRF clinical covariates (age, sex, MoCA, UPSIT) are not available in the MOESM4 supplementary data.", "adjudication_note": "", "report_url": "/assets/reports/parkinson-plasma-prodromal-panel-r4.pdf", "report_kind": "pdf" }, { "id": "parkinson-plasma-prodromal-panel-r4/H4", "run": "parkinson-plasma-prodromal-panel-r4", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "HR directions of 6 UKB-Olink-overlapping proteins concordant between Hällqvist iRBD conversion and Gan 2025 UKB incident PD (>=4/6, p<0.05).", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "**Result: NOT SUPPORTED (1/6 concordant, 17%).**", "adjudication_note": "Hällqvist-side HRs are the run's own Cox HRs from label-contaminated MOESM4 data (published conversion HRs unavailable).", "report_url": "/assets/reports/parkinson-plasma-prodromal-panel-r4.pdf", "report_kind": "pdf" }, { "id": "parkinson-plasma-prodromal-panel-r4/H5", "run": "parkinson-plasma-prodromal-panel-r4", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "At least one functional sub-panel achieves 5-fold CV AUC >0.75 (failure if all <=0.60).", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "**Result: NOT SUPPORTED (no sub-panel exceeds AUC = 0.75).**", "adjudication_note": "Sub-panel AUCs 0.596/0.590/0.457; same label-contamination caveat as H1 applies.", "report_url": "/assets/reports/parkinson-plasma-prodromal-panel-r4.pdf", "report_kind": "pdf" }, { "id": "parkinson-prs-portability-r1/H1", "run": "parkinson-prs-portability-r1", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "EUR 1000G LDpred-funct PRS liability-R2 within ±0.05 of Saffie-Awad 2025 EUR benchmark (AUC 0.621), bootstrap equivalence test", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "\"reasons\": \"contract: missing: results record, analysis summary, figure legends, analysis code, summary, completion flag\"", "adjudication_note": "Run halted at EXECUTE stage 3 (required stage outputs missing; no results record in successive EXECUTE stages); hypothesis never tested.", "report_url": null, "report_kind": null }, { "id": "parkinson-prs-portability-r1/H2", "run": "parkinson-prs-portability-r1", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "EAS/EUR ancestry-decay ratio within ±0.10 of Saffie-Awad ratio 0.931", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "\"reasons\": \"contract: missing: results record, analysis summary, figure legends, analysis code, summary, completion flag\"", "adjudication_note": "Run halted at EXECUTE stage 3 (required stage outputs missing; no results record in successive EXECUTE stages); hypothesis never tested.", "report_url": null, "report_kind": null }, { "id": "parkinson-prs-portability-r1/H3", "run": "parkinson-prs-portability-r1", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Storm 2025 protein-MR overlay adds ΔR2 >= 0.01 in EUR", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "\"reasons\": \"contract: missing: results record, analysis summary, figure legends, analysis code, summary, completion flag\"", "adjudication_note": "Run halted at EXECUTE stage 3 (required stage outputs missing; no results record in successive EXECUTE stages); hypothesis never tested.", "report_url": null, "report_kind": null }, { "id": "parkinson-prs-portability-r1/H4", "run": "parkinson-prs-portability-r1", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "Kim 2024 multi-ancestry PRS not worse than Nalls 2019 EUR-only PRS in EUR (DeLong p>0.10, Kim>=Nalls)", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "\"reasons\": \"contract: missing: results record, analysis summary, figure legends, analysis code, summary, completion flag\"", "adjudication_note": "Run halted at EXECUTE stage 3 (required stage outputs missing; no results record in successive EXECUTE stages); hypothesis never tested.", "report_url": null, "report_kind": null }, { "id": "parkinson-prs-portability-r1/H5", "run": "parkinson-prs-portability-r1", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Bootstrap AUC-equivalent CI width >0.15 for at least one sub-population with n<200", "verdict": "Not tested (run did not execute)", "outcome": "not_run", "outcome_class": "not tested", "evidence_quote": "\"reasons\": \"contract: missing: results record, analysis summary, figure legends, analysis code, summary, completion flag\"", "adjudication_note": "Run halted at EXECUTE stage 3 (required stage outputs missing; no results record in successive EXECUTE stages); hypothesis never tested.", "report_url": null, "report_kind": null }, { "id": "parkinson-prs-portability-r3/H1", "run": "parkinson-prs-portability-r3", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "EUR 1000G analytical PRS liability-R2 (Kim 2024, LDpred) within ±0.05 of Saffie-Awad 2025 EUR benchmark (AUC 0.621)", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "[EUR] R²_obs=0.062550 | R²_L=0.026740 | AUC=0.5467 | 95% CI=[0.5440, 0.5501]", "adjudication_note": "Latest stage EXECUTE stage 9 (liftover + all-chrom AFs fixed) gives AUC 0.547 vs benchmark 0.621 (deviation_auc -0.074349); EXECUTE stage 4 and reviewed report also REJECTED (AUC 0.548, -0.073). Stage 9 lacks analysis summary/completion flag (stage incomplete) but results record is complete.", "report_url": "/assets/reports/parkinson-prs-portability-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-prs-portability-r3/H2", "run": "parkinson-prs-portability-r3", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "EAS/EUR analytical AUC ratio within ±0.10 of Saffie-Awad ratio 0.931", "verdict": "Supported", "outcome": "supported", "outcome_class": "positive", "evidence_quote": "\"ratio_eas_over_eur\": 0.992253,", "adjudication_note": "Rule met formally (deviation +0.061 within ±0.10), but ratio CI [0.984, 1.000] excludes 0.931 and EAS= 0.01", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "The Storm 2025 (Brain 148:2412) supplementary pQTL-instrumented gene list is not available in `storm_2025_pd_targets.json` (empty array). H3 cannot be evaluated.", "adjudication_note": "DEFERRED in stages 4 and 9 (recorded H3 verdict: DEFERRED).", "report_url": "/assets/reports/parkinson-prs-portability-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-prs-portability-r3/H4", "run": "parkinson-prs-portability-r3", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "Multi-ancestry Kim 2024 PRS not significantly outperformed by EUR-only Nalls 2019 PRS in EUR stratum", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "[EUR] R²_obs=0.092491 | R²_L=0.039539 | AUC=0.5570 | 95% CI=[0.5539, 0.5608]", "adjudication_note": "DISCREPANCY: stage 9 code labels H4 SUPPORTED, but with corrected Nalls N_eff (145177) Nalls AUC 0.557 > Kim 0.547; results record delta_kim2024_vs_nalls2019 = -0.01032, CI [-0.014894, -0.005571] (Nalls significantly better) -> pre-registered REJECTED condition; reported delong_p=1.0 is the Kim>Nalls direction. Reviewed report (stage 4 data) said REVERSED, driven by an N_eff artefact. Analytical (label-free) AUCs; interpret cautiously.", "report_url": "/assets/reports/parkinson-prs-portability-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-prs-portability-r3/H5", "run": "parkinson-prs-portability-r3", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Bootstrap AUC CI width >0.15 for at least one ancestry with n<200 (CI honesty)", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "H5 is rejected — not because uncertainty is genuinely small, but because the chi-squared parametric bootstrap models uncertainty in a chi-squared sampling model", "adjudication_note": "Formal rule outcome REJECTED in stages 4 and 9 (AAC CI width ~0.011-0.014), but the run itself states the bootstrap measures analytical sensitivity, not sampling uncertainty (no individual-level labelled genotypes), so the test cannot answer the question. Could also be classed NOT_SUPPORTED by the letter of the rule.", "report_url": "/assets/reports/parkinson-prs-portability-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-scenic-regulons-r1/H1", "run": "parkinson-scenic-regulons-r1", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "Top-20 Fullard SNpc-DA PD regulons replicate same-sign in all 3 held-out atlases (>=3 regulons) with binomial p<0.01", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "3/20 TFs (15%) show sign agreement in both — no better than a null of 50% sign-agreement per pair (binomial p = 0.785)", "adjudication_note": "Pre-registered design not executable: Fullard SNpc discovery atlas unavailable (Adams n=4 PD used), CollecTRI/ULM instead of pySCENIC/AUCell, 2 of 3 replication atlases. Chance-level result (p vs shuffled 0.919); run calls it 'inconclusive rather than falsified' / underpowered. stage 4 (basis of the report) gave 9/20 in 1 atlas, p=0.748. Arguably NOT_TESTED_DATA (proxy test).", "report_url": "/assets/reports/parkinson-scenic-regulons-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-scenic-regulons-r1/H2", "run": "parkinson-scenic-regulons-r1", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "Consensus PD-up regulon TFs enriched (BH q<0.05) for Kim 2024 fine-mapped PD-risk genes", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "This is a proxy test, not the pre-registered test. Conclusion about H2 is inconclusive pending the actual Kim 2024 supplementary table.", "adjudication_note": "Kim 2024 fine-mapping table not retrieved; OpenTargets proxy gave 0 overlaps, q=1.0 (run labelled NOT_SUPPORTED).", "report_url": "/assets/reports/parkinson-scenic-regulons-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-scenic-regulons-r1/H3", "run": "parkinson-scenic-regulons-r1", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Per-donor consensus PD-up regulon activity correlates (rho>0.3) with AGTR1+ DA depletion", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "INAPPLICABLE. Prior workspace `parkinson-da-vulnerability` AUCell scores not available in this execution environment.", "adjudication_note": "", "report_url": "/assets/reports/parkinson-scenic-regulons-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-scenic-regulons-r1/H4", "run": "parkinson-scenic-regulons-r1", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "Leave-one-atlas-out RF on regulon scores classifies PD donors with mean AUC>=0.70 and CI excluding 0.5", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "Mean AUC = 0.808 meets the ≥ 0.70 threshold, but the pre-registration criterion required CI lower bound > 0.5. With only 2 LOO folds, bootstrap CI lower bound = 0.25 (< 0.5).", "adjudication_note": "Run labels NOT_SUPPORTED; 2 folds/16 donors instead of 4-fold LOO, CI [0.25,1.0] uninformative (run attributes to data limitation). Could be NOT_SUPPORTED by the letter of the rule.", "report_url": "/assets/reports/parkinson-scenic-regulons-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-scenic-regulons-r1/H5", "run": "parkinson-scenic-regulons-r1", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "H1 replication count varies by <=1 across Leiden gamma 0.4/0.8/1.2", "verdict": "Supported", "outcome": "supported", "outcome_class": "positive", "evidence_quote": "SUPPORTED. Swing = 1 ≤ pre-registered threshold of 1.", "adjudication_note": "Robustness of a chance-level count (2-3/20); report (stage 4 data) reported swing=0.", "report_url": "/assets/reports/parkinson-scenic-regulons-r1.pdf", "report_kind": "pdf" }, { "id": "parkinson-tcell-foothold-r2/H1", "run": "parkinson-tcell-foothold-r2", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "Ma 2025 clonal CD8+ T-cell module PD-up (FDR<0.1) in >=3/4 independent snRNA-seq atlases, beating shuffled-label null", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "The primary hypothesis is not evaluable with the data currently in the shared cache.", "adjudication_note": "Run labelled NOT SUPPORTED (0/1 atlases), but only Fullard tested and its leukocytes were DMNX-dominated with zero SNpc cells; Kamath/Wang/Adams not downloaded (file size/run budget). Arguably NOT_TESTED_DATA.", "report_url": null, "report_kind": null }, { "id": "parkinson-tcell-foothold-r2/H2", "run": "parkinson-tcell-foothold-r2", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "T-cell module region ranking SNpc > M1 > V1 ≈ DMNX in Fullard (Spearman rho>=0.5, perm p<0.05)", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "ρ = 0.500, permutation p = 0.505.", "adjudication_note": "Run labelled NOT SUPPORTED; SNpc absent (0 leukocytes), only 3 regions so p<0.05 is unreachable.", "report_url": null, "report_kind": null }, { "id": "parkinson-tcell-foothold-r2/H3", "run": "parkinson-tcell-foothold-r2", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Per-donor T-cell module score correlates with AGTR1+ DA loss (rho>0.3, p<0.05) in >=2/4 atlases", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "The Census query fetched only leukocyte-annotated cells; dopaminergic neurons (AGTR1+ DA cluster) were not downloaded.", "adjudication_note": "DEFERRED; data not fetched (could be classed NOT_TESTED_OTHER).", "report_url": null, "report_kind": null }, { "id": "parkinson-tcell-foothold-r2/H4", "run": "parkinson-tcell-foothold-r2", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "Visium spots high in T-cell module co-enriched for reactive-astrocyte markers (rho>=0.3)", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "GSE243639 (Martirosyan 2024 Visium data) RAW.tar (1.2 GB) was not downloaded.", "adjudication_note": "DEFERRED; the sibling run later found GSE243639 is snRNA-seq, not Visium.", "report_url": null, "report_kind": null }, { "id": "parkinson-tcell-foothold-r2/H5", "run": "parkinson-tcell-foothold-r2", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Negative control: exhaustion module NOT PD-enriched (FDR>0.1) in >=3/4 atlases", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "the exhaustion module (PDCD1, HAVCR2, LAG3, TOX, TIGIT) shows mean PD − ctrl difference of +0.012, Wilcoxon padj = 1.000.", "adjudication_note": "Run claims SUPPORTED, but the rule needs >=3/4 atlases and only 1 (wrong-tissue) atlas was tested.", "report_url": null, "report_kind": null }, { "id": "parkinson-tcell-foothold-r3/H1", "run": "parkinson-tcell-foothold-r3", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "Ma 2025 clonal CD8+ T-cell module PD-up (FDR<0.1, log2FC>0) in >=3/4 independent atlases, Δ vs shuffled-label null CI excluding 0", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "Zero of two testable atlases (Wang 2024 and Fullard 2024) show both log2FC > 0 and FDR < 0.1", "adjudication_note": "Also 0/3 with Martirosyan extension; Fullard (62 PD/17 ctrl) null, Cohen d -0.30. Kamath not tested (matrix not in cache), Adams excluded (1 PD donor).", "report_url": "/assets/reports/parkinson-tcell-foothold-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-tcell-foothold-r3/H2", "run": "parkinson-tcell-foothold-r3", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "T-cell module follows revised region rank GPi>=M1>PFC>DMNX≈V1 in Fullard (rho>0.5, perm p<0.05)", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "The pre-registered rank order (GPi > M1 > PFC > DMNX > V1) does not match the observed median scores (ρ = −0.10, p = 0.60).", "adjudication_note": "", "report_url": "/assets/reports/parkinson-tcell-foothold-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-tcell-foothold-r3/H3", "run": "parkinson-tcell-foothold-r3", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "Per-donor T-cell module score correlates with AGTR1+ DA-loss (rho>0.3, perm p<0.05) in >=2/4 atlases", "verdict": "Not supported", "outcome": "not_supported", "outcome_class": "negative", "evidence_quote": "No atlas meets the pre-registered criterion of ρ > 0.3 and permutation p < 0.05.", "adjudication_note": "Very small donor n (5, 5, 15); Fullard rho -0.40 (opposite direction). Somewhat underpowered.", "report_url": "/assets/reports/parkinson-tcell-foothold-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-tcell-foothold-r3/H4", "run": "parkinson-tcell-foothold-r3", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "Spatial T-cell module x reactive-astrocyte co-localisation (pre-registered as DEFERRED)", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "The Martirosyan 2024 dataset (GSE243639) is snRNA-seq, not Visium spatial transcriptomics.", "adjudication_note": "Ma 2025 Visium likely dbGaP-restricted; deferred at PLAN.", "report_url": "/assets/reports/parkinson-tcell-foothold-r3.pdf", "report_kind": "pdf" }, { "id": "parkinson-tcell-foothold-r3/H5", "run": "parkinson-tcell-foothold-r3", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Negative control: exhaustion module fails to replicate (log2FC<=0 or FDR>=0.1) in >=3 atlases", "verdict": "Supported", "outcome": "supported", "outcome_class": "positive", "evidence_quote": "The failure of H5 to show a false-positive enrichment is expected (and reassuring), but the failure of H1 means the negative control comparison is moot — both modules are null.", "adjudication_note": "Rule met on 3 atlases (Wang, Fullard, Martirosyan; results record H5 exhaustion replication rate 0.0) but uninformative because H1 is null.", "report_url": "/assets/reports/parkinson-tcell-foothold-r3.pdf", "report_kind": "pdf" }, { "id": "pd-vatpase-lysosomal-compensation-r1/H1", "run": "pd-vatpase-lysosomal-compensation-r1", "disease": "PD", "hypothesis_id": "H1", "origin": "plan", "hypothesis": "V-ATPase CLEAR module UP (mean log2FC>0, >=6 subunits up, perm p at floor) in LRRK2 G2019S isogenic iPSC-DA, GSE167335", "verdict": "Supported", "outcome": "supported", "outcome_class": "positive", "evidence_quote": "(direction): Mean log2FC = +0.4846 (95% CI +0.182 to +0.787), 8/9 subunits individually up, permutation p = 0.167 at its achievable floor.", "adjudication_note": "Pre-registered direction rule met at n=2+2 (no formal significance possible). Knowledge-graph nodes = supported. CAVEAT: Δ vs prior = -0.0004; report itself questions whether GSE167335 is independent of the original cohort (possible re-analysis of the same data).", "report_url": "/campaign/runs/pd-vatpase-lysosomal-compensation-r1/report/", "report_kind": "html" }, { "id": "pd-vatpase-lysosomal-compensation-r1/H2", "run": "pd-vatpase-lysosomal-compensation-r1", "disease": "PD", "hypothesis_id": "H2", "origin": "plan", "hypothesis": "V-ATPase module higher in GBA-N370S vs control iPSC-DA in E-MTAB-7303", "verdict": "Not testable (data)", "outcome": "not_testable", "outcome_class": "not tested", "evidence_quote": "E-MTAB-7303 (pre-registered H2 cohort) remains BLOCKED — raw FASTQ only, no alignment tools installed.", "adjudication_note": "Only proxy-tested post hoc in GSE62642 (n=4 vs 2): module d = -0.042, 95% CI [-2.531, 1.563], NULL/underpowered. Knowledge-graph nodes = inconclusive. If the proxy is accepted, verdict would be INCONCLUSIVE (underpowered null).", "report_url": "/campaign/runs/pd-vatpase-lysosomal-compensation-r1/report/", "report_kind": "html" }, { "id": "pd-vatpase-lysosomal-compensation-r1/H3", "run": "pd-vatpase-lysosomal-compensation-r1", "disease": "PD", "hypothesis_id": "H3", "origin": "plan", "hypothesis": "iPSC-locked V-ATPase module higher in PD than control postmortem SN DA neurons (GSE157783); AUC and effect CIs exclude null", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "AUC = 1.000 with CI = [1.0, 1.0] is uninformative due to complete separation at this sample size.", "adjudication_note": "Letter of the rule met (d=+5.14, CI [5.142, 15.558]; AUC CI [1,1]) and graph status 'supported', but CIs are degenerate at n=2+2, perm p=0.167; run states formal inference is impossible.", "report_url": "/campaign/runs/pd-vatpase-lysosomal-compensation-r1/report/", "report_kind": "html" }, { "id": "pd-vatpase-lysosomal-compensation-r1/H4", "run": "pd-vatpase-lysosomal-compensation-r1", "disease": "PD", "hypothesis_id": "H4", "origin": "plan", "hypothesis": "V-ATPase shift is DA-neuron selective (DA-vs-other contrast CI excludes 0)", "verdict": "Inconclusive", "outcome": "inconclusive", "outcome_class": "inconclusive", "evidence_quote": "DA vs non-DA contrast: Δd = +4.065, 95% CI [−174.663, +15.394], p = 0.741", "adjudication_note": "Run verdict GLOBAL/inconclusive; pre-registered rule would call this NULL; n=2+2 per cell type.", "report_url": "/campaign/runs/pd-vatpase-lysosomal-compensation-r1/report/", "report_kind": "html" }, { "id": "pd-vatpase-lysosomal-compensation-r1/H5", "run": "pd-vatpase-lysosomal-compensation-r1", "disease": "PD", "hypothesis_id": "H5", "origin": "plan", "hypothesis": "Sensitivity/power decomposition: replication verdict robust to gene-set and normalisation choices; cohort power adequacy", "verdict": "Partially supported", "outcome": "partial", "outcome_class": "positive (partial)", "evidence_quote": "No cohort in this study can achieve formal statistical significance at α = 0.05 in the available data.", "adjudication_note": "Descriptive sub-analyses with no formal decision rule. H1 direction robust to normalisation (+0.485 vs +0.490); gene-set split not robust (V0-only down -1.35 in GSE157783 while 9-gene up); no cohort adequately powered.", "report_url": "/campaign/runs/pd-vatpase-lysosomal-compensation-r1/report/", "report_kind": "html" } ]