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On metrics for subpopulation detection in single-cell and spatial omics data

2024/12/03 by Siyuan Luo, Pierre‐Luc Germain, Ferdinand von Meyenn +1 · 1 voice
Biochemistry, Genetics and Molecular Biology · Environmental Science · #Single-cell and spatial transcriptomics #Health, Environment, Cognitive Aging #Bioinformatics and Genomic Networks

paper · doi:10.1101/2024.11.28.625845

openalex publication_date 2024/12/03 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/15

Abstract

Benchmarks are crucial to understanding the strengths and weaknesses of the growing number of tools for single-cell and spatial omics analysis. A key task is to distinguish subpopulations within complex tissues, where evaluation typically relies on \em external clustering validation metrics. Different metrics often lead to inconsistencies between rankings, highlighting the importance of understanding the behavior and biological implications of each metric. In this work, we provide a framework for systematically understanding and selecting validation metrics for single-cell data analysis, addressing tasks such as creating cell embeddings, constructing graphs, clustering, and spatial domain detection. Our discussion centers on the desirable properties of metrics, focusing on biological relevance and potential biases. Using this framework, we not only analyze existing metrics, but also develop novel ones. Delving into domain detection in spatial omics data, we develop new external metrics tailored to spatially-aware measurements. Additionally, a Bioconductor R package, poem, implements all the metrics discussed. While we focus on single-cell omics, much of the discussion is of broader relevance to other types of high-dimensional data.

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