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Chunk #43 — Results — Optimization, validation, and accuracy estimation of the reference panel and digital deconvolution method

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Genetic variants associated with Alzheimer's disease confer different cerebral cortex cell-type population structure.
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We first validated the accuracy to predict neuronal composition by generating RNA-seq for eight iPSC-derived cortical neurons (see “Methods”). We observed an accurate prediction in these independent cell lines (mean neuronal proportion = 94.8%, s.d. = 1.1%; Additional file 1: Figure S4a). We also ascertained the cellular composition of mRNA extracted from the barrel cortex neurons isolated by TRAP in 24 mice. TRAP is a method that captures cell-type-specific mRNA translation by purifying tagged ribosomal subunit and capturing the mRNA it bound to [45]. We observed an average of neuronal proportion = 96.7% and s.d. = 1.2% (Additional file 1: Figure S4b). Similarly, we assessed the RNA-seq data generated for iPSC-derived microglia (n = 10) deposited in the AMP-AD portal (synapse ID: syn7203233) and inferred their cellular population structure and observed a mean microglia proportion = 86.6% and s.d. = 7.1% (Additional file 1: Figure S4c).