Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.20 (overall 0.12) | 0.20 |
| cell type Human Protein Atlas | enriched in the midbrain (75 nTPM), where the nigral dopamine neurons sit | 0.90 |
| chemistry Open Targets | reachable by antibody | 0.36 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 1 Parkinson's papers of 99 | 0.91 |
| pathways Reactome | 2 pathways; mostly other | 0.30 |
Knock down and overexpress AMIGO2 in dopamine neurons; measure a transcriptome-wide state shift (bulk RNA-seq) and survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils.
- Cell type
- dopamine neurons
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- a transcriptome-wide state shift (bulk RNA-seq)
- Functional readout
- survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils
- 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 AMIGO2 in iPSC-derived midbrain dopamine neurons (FOXA2+, LMX1A+, TH+); n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- AMIGO2 in dopamine neurons, braak+0.58 (p 0.102) → +0.20 (p 0.603)receipt 2308
Swarm cases
receipt 2308: AMIGO2 in dopamine neurons, braak
- power
- full sample +0.43 (p 0.074, n 18), 95% CI -0.04 to +0.75. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.38 (p 0.118, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.36 (p 0.142, n 18). could be the mix.
- skeptic
- leave-one-out range +0.35 to +0.58, sign flips 0; without severely affected donors +0.43 (p 0.074, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for AMIGO2 in dopamine neurons.
case closed: nothing better to follow up.
Receipts
loading the receipts