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Automatic cell-type harmonization and integration across Human Cell Atlas datasets

2023/12/01 by Chuan Xu, Martin Prete, Simone Webb +6 · 4 citations
Biochemistry, Genetics and Molecular Biology · Computer Science · #Cell Image Analysis Techniques #Single-cell and spatial transcriptomics #AI in cancer detection

paper · doi:10.1016/j.cell.2023.11.026

Abstract

Harmonizing cell types across the single-cell community and assembling them into a common framework is central to building a standardized Human Cell Atlas. Here, we present CellHint, a predictive clustering tree-based tool to resolve cell-type differences in annotation resolution and technical biases across datasets. CellHint accurately quantifies cell-cell transcriptomic similarities and places cell types into a relationship graph that hierarchically defines shared and unique cell subtypes. Application to multiple immune datasets recapitulates expert-curated annotations. CellHint also reveals underexplored relationships between healthy and diseased lung cell states in eight diseases. Furthermore, we present a workflow for fast cross-dataset integration guided by harmonized cell types and cell hierarchy, which uncovers underappreciated cell types in adult human hippocampus. Finally, we apply CellHint to 12 tissues from 38 datasets, providing a deeply curated cross-tissue database with ∼3.7 million cells and various machine learning models for automatic cell annotation across human tissues.

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