Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.00 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in astrocytes (2107 nCPM) | 1.00 |
| 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 | 2 Parkinson's papers of 203 | 0.85 |
| pathways Reactome | 1 pathway; mostly iron and oxidative stress | 0.80 |
Knock down and overexpress TNIK in astrocytes; measure reactive oxygen species (CellROX) and lipid peroxidation and labile iron 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
- reactive oxygen species (CellROX) and lipid peroxidation and labile iron
- Functional readout
- α-synuclein uptake and degradation, and dopamine neuron survival in co-culture
- Rule-out
- If neither arm moves reactive oxygen species (CellROX) 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 TNIK in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: reactive oxygen species (CellROX) and lipid peroxidation and labile iron; 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
- TNIK in astrocytes, braak-0.09 (p 0.815) → +0.50 (p 0.174)receipt 14616
- TNIK in dopamine neurons, braak-0.14 (p 0.714) → +0.29 (p 0.442)receipt 14617
Swarm cases
receipt 14617: TNIK in dopamine neurons, braak
- power
- full sample +0.13 (p 0.609, n 18), 95% CI -0.36 to +0.56. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.13 (p 0.621, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.11 (p 0.652, n 18). could be the mix.
- skeptic
- leave-one-out range -0.00 to +0.24, sign flips 1; without severely affected donors +0.13 (p 0.609, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for TNIK in dopamine neurons.
case closed: nothing better to follow up.
receipt 14616: TNIK in astrocytes, 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 0.658, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: +0.21 (p 0.393, n 18). could be the mix.
- skeptic
- leave-one-out range +0.05 to +0.27, 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 TNIK in astrocytes.
case closed: nothing better to follow up.
Receipts
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