Affiliation:
1. Department of Computer Science, City University of Hong Kong , 83 Tat Chee Ave, Kowloon Tong, Hong Kong, China
2. City University of Hong Kong Shenzhen Research Institute , Shenzhen, 518057, Guangdong, China
Abstract
Abstract
Cells possess functional diversity hierarchically. However, most single-cell analyses neglect the nested structures while detecting and visualizing the functional diversity. Here, we incorporate cell hierarchy to study functional diversity at subpopulation, club (i.e., sub-subpopulation), and cell layers. Accordingly, we implement a package, SEAT, to construct cell hierarchies utilizing structure entropy by minimizing the global uncertainty in cell–cell graphs. With cell hierarchies, SEAT deciphers functional diversity in 36 datasets covering scRNA, scDNA, scATAC, and scRNA-scATAC multiome. First, SEAT finds optimal cell subpopulations with high clustering accuracy. It identifies cell types or fates from omics profiles and boosts accuracy from 0.34 to 1. Second, SEAT detects insightful functional diversity among cell clubs. The hierarchy of breast cancer cells reveals that the specific tumor cell club drives AREG-EGFT signaling. We identify a dense co-accessibility network of cis-regulatory elements specified by one cell club in GM12878. Third, the cell order from the hierarchy infers periodic pseudo-time of cells, improving accuracy from 0.79 to 0.89. Moreover, we incorporate cell hierarchy layers as prior knowledge to refine nonlinear dimension reduction, enabling us to visualize hierarchical cell layouts in low-dimensional space.
Funder
CityU/UGC Research Matching Grant Scheme
The Science Technology and Innovation Committee of Shenzhen Municipality
Publisher
Oxford University Press (OUP)
Cited by
4 articles.
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