Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.07 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including astrocytes; strongest in late spermatids | 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 | 4 Parkinson's papers of 384 | 0.79 |
| pathways Reactome | 1 pathway; mostly lysosome and autophagy | 1.00 |
Knock down and overexpress EEF2K in astrocytes; measure glucocerebrosidase (GCase) activity and LC3-II and p62 flux 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
- glucocerebrosidase (GCase) activity and LC3-II and p62 flux
- Functional readout
- α-synuclein uptake and degradation, and dopamine neuron survival in co-culture
- Rule-out
- If neither arm moves glucocerebrosidase (GCase) activity 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 EEF2K in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: glucocerebrosidase (GCase) activity and LC3-II and p62 flux; 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
- EEF2K in astrocytes, braak+0.07 (p 0.855) → +0.23 (p 0.545)receipt 3687
- EEF2K in dopamine neurons, braak-0.02 (p 0.964) → -0.11 (p 0.787)receipt 3688
Swarm cases
receipt 3688: EEF2K in dopamine neurons, braak
- power
- full sample -0.02 (p 0.928, n 18), 95% CI -0.48 to +0.45. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.06 (p 0.814, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.04 (p 0.881, n 18). could be the mix.
- skeptic
- leave-one-out range -0.14 to +0.10, sign flips 6; without severely affected donors -0.02 (p 0.928, n 18). fragile.
- cell type
- strongest in microglia: -0.75 (p 3.5e-4, n 18) vs -0.02 in dopamine neurons. proposing microglia.
- axis
- no measure beats "tracks Braak Lewy-body stage" for EEF2K in dopamine neurons.
follow-up registered; not confirmed in substantia nigra, an independent cohort.
follow-up EEF2K · microglia · braak: substantia nigra, an independent cohort (already registered)
receipt 3687: EEF2K in astrocytes, braak
- power
- full sample +0.12 (p 0.633, n 18), 95% CI -0.37 to +0.56. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.06 (p 0.814, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: +0.16 (p 0.521, n 18). could be the mix.
- skeptic
- leave-one-out range -0.01 to +0.23, sign flips 2; without severely affected donors +0.12 (p 0.633, n 18). fragile.
- cell type
- strongest in microglia: -0.75 (p 3.5e-4, n 18) vs +0.12 in astrocytes. proposing microglia.
- axis
- no measure beats "tracks Braak Lewy-body stage" for EEF2K in astrocytes.
follow-up registered; not confirmed in substantia nigra, an independent cohort.
follow-up EEF2K · microglia · braak: substantia nigra, an independent cohort (Parkinson's or LBD vs controls) -0.65 p 0.021 (needs p < 5.2e-4)
Receipts
loading the receipts