Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.02 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocytes; strongest in extravillous trophoblasts | 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 282 | 0.91 |
| pathways Reactome | 5 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress HSPA2 in oligodendrocytes; measure evoked dopamine release and dopamine transporter uptake and α-synuclein uptake and myelin basic protein output under oxidative stress.
- Cell type
- oligodendrocytes
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- evoked dopamine release and dopamine transporter uptake
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves evoked dopamine release 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 HSPA2 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: evoked dopamine release and dopamine transporter uptake; α-synuclein uptake and myelin basic protein output under oxidative stress. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- HSPA2 in dopamine neurons, braak+0.19 (p 0.618) → -0.16 (p 0.685)receipt 7586
- HSPA2 in oligodendrocytes, braak+0.30 (p 0.438) → -0.31 (p 0.416)receipt 7585
Swarm cases
receipt 7586: HSPA2 in dopamine neurons, braak
- power
- full sample +0.15 (p 0.549, n 18), 95% CI -0.34 to +0.58. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.11 (p 0.652, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.15 (p 0.549, n 18). could be the mix.
- skeptic
- leave-one-out range +0.07 to +0.32, sign flips 0; without severely affected donors +0.15 (p 0.549, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for HSPA2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 7585: HSPA2 in oligodendrocytes, braak
- power
- full sample -0.07 (p 0.774, n 18), 95% CI -0.52 to +0.41. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.02 (p 0.935, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.09 (p 0.709, n 18). could be the mix.
- skeptic
- leave-one-out range -0.21 to +0.03, sign flips 1; without severely affected donors -0.07 (p 0.774, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for HSPA2 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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