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Chunk #40 — Results — Development of a reference panel to estimate brain cellular population structure

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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 tried to create a transcriptome-wide reference panel by selecting the genes that are differentially expressed among cell types [26, 60, 62]. However, the species heterogeneity of the reference samples we compiled ruled out this attempt, as the PCA showed that differences between the human and mice donor samples dominated the transcriptome-wide profiles (Additional file 1: Figure S1a). For this reason, we curated a list of marker genes that have been described to tag these distinct cell types [31, 55, 56] (Additional file 1: Table S3). A visual inspection of the expression of these marker genes in the samples we compiled suggested a divergent transcriptomic profile among the cell types (Additional file 1: Figure S2a). The PCA showed that their expression was sufficient to cluster samples of neurons, astrocytes, oligodendrocytes, and microglia with their respective cell types, regardless of the species of the reference samples (Additional file 1: Figure S1b; Additional file 1: Table S2). We observed that some samples did not cluster with their expected cell types and coincidently the LOOCV indicated that these samples had an expression