Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.35 (overall 0.22) | 0.35 |
| cell type Human Protein Atlas | cell type enhanced, including astrocytes; strongest in renal connecting tubule cells | 0.75 |
| chemistry Open Targets | reachable by antibody | 0.45 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | in no curated pathway | 0.00 |
Knock down and overexpress FAM171A1 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 FAM171A1 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.
Sealed predictions
- FAM171A1 in dopamine neurons, braak+0.11 (p 0.779) → -0.90 (p 0.001)receipt 1939
- FAM171A1 in astrocytes, braak-0.39 (p 0.297) → -0.27 (p 0.489)receipt 1938
Swarm cases
receipt 1939: FAM171A1 in dopamine neurons, braak
- power
- full sample -0.57 (p 0.014, n 18), 95% CI -0.82 to -0.14. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: -0.60 (p 0.0089, n 18). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.53 (p 0.023, n 18). not the mix.
- skeptic
- leave-one-out range -0.74 to -0.51, sign flips 0; without severely affected donors -0.57 (p 0.014, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for FAM171A1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 1938: FAM171A1 in astrocytes, braak
- power
- full sample -0.35 (p 0.150, n 18), 95% CI -0.70 to +0.14. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.34 (p 0.164, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: -0.39 (p 0.111, n 18). could be the mix.
- skeptic
- leave-one-out range -0.51 to -0.26, sign flips 0; without severely affected donors -0.35 (p 0.150, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for FAM171A1 in astrocytes.
case closed: nothing better to follow up.
Receipts
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