scAI-SNP: a method for inferring ancestry from single-cell data.

BMC methods
Authors
Keywords
Abstract

BACKGROUND: Collaborative efforts, such as the Human Cell Atlas, are rapidly accumulating large amounts of single-cell data. To ensure that single-cell atlases are representative of human genetic diversity, we need to determine the ancestry of the donors from whom single-cell data are generated. Self-reporting of race and ethnicity, although important, can be biased and is not always available for the datasets already collected.METHODS: Here, we introduce scAI-SNP, a tool to infer ancestry directly from single-cell genomics data. To train scAI-SNP, we identified 4.5 million ancestry-informative single-nucleotide polymorphisms (SNPs) in the 1000 Genomes Project dataset across 3201 individuals from 26 population groups. For a query single-cell dataset, scAI-SNP uses these ancestry-informative SNPs to compute the contribution of each of the 26 population groups to the ancestry of the donor from whom the cells were obtained.RESULTS: Using diverse single-cell datasets with matched whole-genome sequencing data, we show that scAI-SNP is robust to the sparsity of single-cell data, can accurately and consistently infer ancestry from samples derived from diverse types of tissues and cancer cells, and can be applied to different modalities of single-cell profiling assays, such as single-cell RNA-seq and single-cell ATAC-seq.DISCUSSION: Finally, we argue that ensuring that single-cell atlases represent diverse ancestry, ideally alongside race and ethnicity, is ultimately important for improved and equitable health outcomes by accounting for human diversity.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s44330-025-00029-4.

Year of Publication
2025
Journal
BMC methods
Volume
2
Issue
1
Pages
10
Date Published
12/2025
ISSN
3004-8729
DOI
10.1186/s44330-025-00029-4
PubMed ID
40401145
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