While single-cell technologies have greatly advanced our comprehension of human brain cell types and functions, studies including large numbers of donors and multiple brain regions are needed to extend our understanding of brain cell heterogeneity.
Integrating atlas-level single-cell data presents a chance to reveal rare cell types and cellular heterogeneity across brain regions. Here we present the Brain Cell Atlas, a comprehensive reference atlas of brain cells, by assembling single-cell data from 70 human and 103 mouse studies of the brain throughout major developmental stages across brain regions, covering over 26.3 million cells or nuclei from both healthy and diseased tissues.
However, integrating large-scale atlases still presents computational challenges, such as modeling the batch effects and reducing technical noise. Batch correction for large-scale data in the expression matrix is computationally expensive, and performing differential expression analysis without accounting for batch effects may lead to bias. A more efficient approach reported recentlyis to model both biology and batch effects in differential expression analysis after data integration.
In metadata, ‘cell_ID’ is defined as the index of the sequencing files. The ‘donor_ID’ provides information that uniquely identifies the donors. The ‘donor_sex’ field contains self-reported sex for postnatal or adult donors, while for fetal samples, sex was classified on the basis of information from the original data . The ‘donor_age’ is classified as months for donors younger than 1 year and as years for postnatal donors older than 1 year.
To optimize the cell type annotation inferred from cross-species comparison, these cell clusters were validated by marker genes. The cells were clustered by Leiden clustering and visualized on UMAP. The well-established cell type markers. This score indicates the number of markers detected in a cell with at least one unique molecular identifier. The cell number decreased quickly when the NPC gene module score was less than 3, and then the change tended to be slow.
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