ID: h-55bc3e94f8
Hypothesis
C1q effector output is determined more by binding partner identity than by subcellular location
Under this model, C1q is a context decoder whose downstream program depends chiefly on the biochemical identity of the complex it forms, such as neuronal pentraxins, Aβ aggregates, apoptotic membranes, or ECM ligands.
EvidencePending (0%)📖 0 cit🗣 1 debates✓ 3 support✗ 2 oppose
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🧪 Overview
Under this model, C1q is a context decoder whose downstream program depends chiefly on the biochemical identity of the complex it forms, such as neuronal pentraxins, Aβ aggregates, apoptotic membranes, or ECM ligands. Spatial localization remains relevant, but as a secondary variable relative to ligand chemistry and complex composition.
🧬 Mechanism
🧬 Curated Mechanism Pathway
Curated pathway from expert analysis
flowchart TD
A["Target Gene: C1QAC1QBC1QCNPTX1NPTX2APPC3"]
B["Molecular Mechanism<br/>Pathway Activation"]
C["Cellular Phenotype<br/>Neuronal / Glial Response"]
D["Network Effect<br/>Circuit-Level Consequence"]
E["Disease Relevance<br/>Neurodegeneration Link"]
A --> B --> C --> D --> E
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style E fill:#1b5e20,stroke:#81c784,color:#81c784⚖️ Evidence
⚖️ Evidence Matrix3 supports2 contradicts
Supports
C1q binds diverse ligands including Aβ, indicating that binding-partner identity can shape downstream complement activation.
Supports
Aβ-C1q complexes activate complement in AD-relevant settings, supporting ligand-specific effector programs.
Supports
Neuronal pentraxins interact with C1q, providing a plausible synaptic ligand axis distinct from plaque-associated ligands.
Contradicts
No decisive CNS study yet demonstrates that ligand identity explains more variance than location when ligand, receiver cell, and complement competence are independently controlled.
Contradicts
Microenvironmental geometry, local complement regulators, and which cell encounters the complex first may rival or exceed ligand identity in determining outcome.
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — C1QA
🧠 GTEx v10 Brain ExpressionJSON
Median TPM across 13 brain regions for C1QA,C1QB,C1QC,NPTX1,NPTX2,APP,C3 from GTEx v10.
💉 Clinical Trials
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for C1QA,C1QB,C1QC,NPTX1,NPTX2,APP,C3.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
💰 Estimated Development
Cost
$0
Timeline
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🏆 Tournament
🏆 Arenas / Elo
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📊 Market Indicators
7d Trend
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Stable
7d Momentum
▼ 0.5%
Volatility
Low
0.0027
Events (7d)
2
Price History
▼8.6%💾 Resource Usage
LLM Tokens
19,754
$0.0593
Total Cost
$0.0593
🔮 Predictions
🔎 Predictions vs Observations2 predictions · 0 with recorded observations
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF C1q is targeted to neuronal dendrites via cell-impermeant crosslinking versus allowed to diffuse freely in extracellular space while binding identical NPTX2 ligand, THEN the downstream complement C | Equivalent C3 deposition regardless of C1q-NPTX2 spatial targeting; opsonization rate difference <15% | — no observation — | pending | 0.55 |
| IF C1q is pre-incubated with neuronal pentraxin 1 (NPTX1) to form C1q-NPTX1 complexes versus pre-incubated with amyloid-beta (APP-derived Aβ1-42) to form C1q-Aβ complexes, THEN human iPSC-derived cort | Differential complement gene expression; C1q-Aβ complexes will upregulate C3 and C4B mRNA 2-3 fold higher than C1q-NPTX1 complexes | — no observation — | pending | 0.60 |
🔮 Falsifiable Predictions (2)
pendingconf 60%
IF C1q is pre-incubated with neuronal pentraxin 1 (NPTX1) to form C1q-NPTX1 complexes versus pre-incubated with amyloid-beta (APP-derived Aβ1-42) to form C1q-Aβ complexes, THEN human iPSC-derived cortical neurons will exhibit significantly different transcriptional profiles of complement-related gen
Predicted outcome: Differential complement gene expression; C1q-Aβ complexes will upregulate C3 and C4B mRNA 2-3 fold higher than C1q-NPTX1 complexes
Falsification: If C1q-NPTX1 and C1q-Aβ complexes produce statistically equivalent complement gene expression (difference <1.2-fold, p > 0.05), the hypothesis that binding partner identity is primary would be falsifi
pendingconf 55%
IF C1q is targeted to neuronal dendrites via cell-impermeant crosslinking versus allowed to diffuse freely in extracellular space while binding identical NPTX2 ligand, THEN the downstream complement C3 opsonization rate on hippocampal neurons will remain unchanged (within 15% variance), indicating l
Predicted outcome: Equivalent C3 deposition regardless of C1q-NPTX2 spatial targeting; opsonization rate difference <15%
Falsification: If targeted C1q-NPTX2 produces ≥40% higher C3 deposition than freely-diffused C1q-NPTX2, location would be the primary determinant rather than ligand identity, falsifying this prediction
▸Metadatasource: v1_phase_c_backfill · origin_type: debate_synthesizer
| source | v1_phase_c_backfill |
| origin_type | debate_synthesizer |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
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