Cell Marker Accordion: interpretable single-cell and spatial omics annotation in health and disease

Abstract Single-cell technologies offer a unique opportunity to explore cellular heterogeneity in health and disease. However, reliable identification of cell types and states represents a bottleneck. Available databases and analysis tools employ dissimilar markers, leading to inconsistent annotatio...

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Main Authors: Emma Busarello, Giulia Biancon, Ilaria Cimignolo, Fabio Lauria, Zuhairia Ibnat, Christian Ramirez, Gabriele Tomè, Marianna Ciuffreda, Giorgia Bucciarelli, Alessandro Pilli, Stefano Maria Marino, Vittorio Bontempi, Federica Ress, Kristin R. Aass, Jennifer VanOudenhove, Luca Tiberi, Maria Caterina Mione, Therese Standal, Paolo Macchi, Gabriella Viero, Stephanie Halene, Toma Tebaldi
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60900-4
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Summary:Abstract Single-cell technologies offer a unique opportunity to explore cellular heterogeneity in health and disease. However, reliable identification of cell types and states represents a bottleneck. Available databases and analysis tools employ dissimilar markers, leading to inconsistent annotations and poor interpretability. Furthermore, current tools focus mostly on physiological cell types, limiting their applicability to disease. We present the Cell Marker Accordion, a user-friendly platform providing automatic annotation and unmatched biological interpretation of single-cell populations, based on consistency weighted markers. We validate our approach on multiple single-cell and spatial datasets from different human and murine tissues, improving annotation accuracy in all cases. Moreover, we show that the Cell Marker Accordion can identify disease-critical cells and pathological processes, extracting potential biomarkers in a wide variety of disease contexts. The breadth of these applications elevates the Cell Marker Accordion as a fast, flexible, faithful and standardized tool to annotate and interpret single-cell and spatial populations in studying physiology and disease.
ISSN:2041-1723