Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.82 (overall 0.58) | 0.82 |
| cell type Human Protein Atlas | cell type enhanced, including astrocytes; strongest in choroid plexus epithelial cells | 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 | 11 Parkinson's papers of 117 | 0.67 |
| pathways Reactome | 1 pathway; mostly other | 0.30 |
Knock down and overexpress ITPKB in astrocytes; measure a transcriptome-wide state shift (bulk RNA-seq) 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
- a transcriptome-wide state shift (bulk RNA-seq)
- Functional readout
- α-synuclein uptake and degradation, and dopamine neuron survival in co-culture
- Rule-out
- If neither arm moves a transcriptome-wide state shift (bulk RNA-seq) 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 ITPKB in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); 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.
Earlier readings: 2026-10-26 0.70; 2026-10-25 0.70; 2026-10-24 0.70; 2026-10-23 0.70.
Sealed predictions
- ITPKB in astrocytes, braak-0.79 (p 0.012) → +0.01 (p 0.982)receipt 0568
- ITPKB in dopamine neurons, braak-0.65 (p 0.058) → -0.83 (p 0.006)receipt 0569
- ITPKB in astrocytes, braak-0.17 (p 0.270) → -0.08 (p 0.629)receipt 0099
- ITPKB in astrocytes, resilience-0.13 (p 0.653) → -0.21 (p 0.448)receipt 0100
Swarm cases
receipt 0569: ITPKB in dopamine neurons, braak
- power
- full sample -0.78 (p 1.4e-4, n 18), 95% CI -0.91 to -0.49. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: -0.78 (p 1.4e-4, n 18). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.78 (p 1.4e-4, n 18). not the mix.
- skeptic
- leave-one-out range -0.83 to -0.75, sign flips 0; without severely affected donors -0.78 (p 1.4e-4, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ITPKB in dopamine neurons.
case closed: nothing better to follow up.
receipt 0568: ITPKB in astrocytes, braak
- power
- full sample -0.34 (p 0.164, n 18), 95% CI -0.70 to +0.15. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.22 (p 0.374, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: -0.32 (p 0.194, n 18). could be the mix.
- skeptic
- leave-one-out range -0.51 to -0.27, sign flips 0; without severely affected donors -0.34 (p 0.164, n 18). fragile.
- cell type
- strongest in dopamine neurons: -0.78 (p 1.4e-4, n 18) vs -0.34 in astrocytes. proposing dopamine neurons.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ITPKB in astrocytes.
follow-up registered; not confirmed in substantia nigra, an independent cohort.
follow-up ITPKB · dopamine neurons · braak: substantia nigra, an independent cohort (Parkinson's or LBD vs controls) -0.07 p 0.790 (needs p < 0.0016)
receipt 0100: ITPKB in astrocytes, resilience
- power
- full sample -0.14 (p 0.474, n 55), 95% CI -0.39 to +0.13. the interval is wide: not enough donors to tell.
- confounder
- adjusted for age, sex and PMI: -0.11 (p 0.570, n 55). does not hold up.
- composition
- astrocytes share of nuclei vs axis +0.34 (p 0.084); controlling for it: -0.21 (p 0.283, n 55). could be the mix.
- skeptic
- leave-one-out range -0.25 to -0.08, sign flips 0; without severely affected donors -0.14 (p 0.479, n 46). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "differs in resilient donors (Lewy pathology, no parkinsonism)" for ITPKB in astrocytes.
case closed: nothing better to follow up.
receipt 0099: ITPKB in astrocytes, braak
- power
- full sample -0.11 (p 0.302, n 84), 95% CI -0.32 to +0.10. the interval sits on zero: probably nothing there.
- confounder
- adjusted for age, sex and PMI: -0.05 (p 0.658, n 84). does not hold up.
- composition
- astrocytes share of nuclei vs axis +0.26 (p 0.016); controlling for it: -0.08 (p 0.486, n 84). could be the mix.
- skeptic
- leave-one-out range -0.15 to -0.09, sign flips 0; without severely affected donors -0.13 (p 0.269, n 75). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ITPKB in astrocytes.
case closed: nothing better to follow up.
Receipts
loading the receipts