Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.01 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including astrocytes; strongest in hepatocytes | 0.75 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 1 Parkinson's papers of 517 | 0.91 |
| pathways Reactome | 5 pathways; mostly immune signalling | 0.90 |
Knock down and overexpress MASP1 in astrocytes; measure IL-1β and TNF release and surface HLA-DR and α-synuclein uptake and degradation, and dopamine neuron survival in co-culture.
- Cell type
- astrocytes
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- IL-1β and TNF release and surface HLA-DR
- Functional readout
- α-synuclein uptake and degradation, and dopamine neuron survival in co-culture
- Rule-out
- If neither arm moves IL-1β by 20% or more against non-targeting and empty-vector controls, across three independent differentiations, the hypothesis is wrong.
- Lab request
- CRISPRi knockdown and lentiviral overexpression of MASP1 in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: IL-1β and TNF release and surface HLA-DR; α-synuclein uptake and degradation, and dopamine neuron survival in co-culture. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- MASP1 in astrocytes, braak-0.05 (p 0.892) → +0.56 (p 0.116)receipt 11351
- MASP1 in dopamine neurons, braak-0.89 (p 0.001) → -0.30 (p 0.426)receipt 11352
Swarm cases
receipt 11352: MASP1 in dopamine neurons, braak
- power
- full sample -0.56 (p 0.015, n 18), 95% CI -0.82 to -0.13. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: -0.56 (p 0.015, n 18). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.73 (p 6.6e-4, n 18). not the mix.
- skeptic
- leave-one-out range -0.64 to -0.51, sign flips 0; without severely affected donors -0.56 (p 0.015, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MASP1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 11351: MASP1 in astrocytes, braak
- power
- full sample +0.23 (p 0.360, n 18), 95% CI -0.27 to +0.63. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.31 (p 0.207, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: +0.34 (p 0.170, n 18). could be the mix.
- skeptic
- leave-one-out range +0.11 to +0.33, sign flips 0; without severely affected donors +0.23 (p 0.360, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MASP1 in astrocytes.
case closed: nothing better to follow up.
Receipts
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