Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.50 (overall 0.32) | 0.50 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocytes; strongest in retinal bipolar cells | 0.75 |
| chemistry Open Targets | reachable by antibody | 0.45 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 5 Parkinson's papers of 156 | 0.76 |
| pathways Reactome | 7 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress DLG2 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 DLG2 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
- DLG2 in oligodendrocytes, braak+0.41 (p 0.271) → +0.47 (p 0.204)receipt 1156
- DLG2 in dopamine neurons, braak+0.06 (p 0.875) → +0.32 (p 0.407)receipt 1157
Swarm cases
receipt 1157: DLG2 in dopamine neurons, braak
- power
- full sample +0.14 (p 0.579, n 18), 95% CI -0.35 to +0.57. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.12 (p 0.646, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.14 (p 0.567, n 18). could be the mix.
- skeptic
- leave-one-out range +0.03 to +0.27, sign flips 0; without severely affected donors +0.14 (p 0.579, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for DLG2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 1156: DLG2 in oligodendrocytes, braak
- power
- full sample +0.57 (p 0.014, n 18), 95% CI +0.14 to +0.82. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: +0.54 (p 0.021, n 18). holds up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.55 (p 0.018, n 18). not the mix.
- skeptic
- leave-one-out range +0.52 to +0.71, sign flips 0; without severely affected donors +0.57 (p 0.014, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for DLG2 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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