Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.46 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocyte progenitor cells; strongest in thymic myoid cells | 0.75 |
| chemistry Open Targets | compounds already reach it: wx-037, pf-04691502, recilisib +21 | 0.90 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 5 Parkinson's papers of 1,453 | 0.76 |
| pathways Reactome | 78 pathways; mostly immune signalling | 0.90 |
Knock down and overexpress PIK3R1 in oligodendrocytes; measure IL-1β and TNF release and surface HLA-DR 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; existing compounds already reach the inhibition arm.
- Molecular readout
- IL-1β and TNF release and surface HLA-DR
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- 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 PIK3R1 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: IL-1β and TNF release and surface HLA-DR; 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
- PIK3R1 in dopamine neurons, braak+0.10 (p 0.802) → -0.23 (p 0.560)receipt 0400
- PIK3R1 in oligodendrocytes, braak+0.26 (p 0.493) → -0.40 (p 0.281)receipt 0399
Swarm cases
receipt 0400: PIK3R1 in dopamine neurons, braak
- power
- full sample -0.15 (p 0.561, n 18), 95% CI -0.57 to +0.34. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.16 (p 0.532, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.12 (p 0.633, n 18). could be the mix.
- skeptic
- leave-one-out range -0.26 to -0.01, sign flips 0; without severely affected donors -0.15 (p 0.561, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PIK3R1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0399: PIK3R1 in oligodendrocytes, braak
- power
- full sample -0.09 (p 0.712, n 18), 95% CI -0.54 to +0.39. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.10 (p 0.680, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.03 (p 0.894, n 18). could be the mix.
- skeptic
- leave-one-out range -0.23 to +0.01, sign flips 3; without severely affected donors -0.09 (p 0.712, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PIK3R1 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
loading the receipts